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ZMPCZM016000.11.08 Applications of TENS in the management of Patients with pain

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  • 1. Applications of Transcutaneous Electrical Nerve Stimulation in the Management of Patients with Pain State-of-the-Art Update MERYL ROTH GERSH and STEVEN L. WOLF Numerous publications devoted to the topic of transcutaneous electrical nerve stimulation (TENS) have appeared since the presentation of a special issue of PHYSICAL THERAPY (December, 1978). This update article addresses contemporary information on efficacy, mode of application, treatment outcomes, and neurophysiological mechanisms relevant to this modality. Investigators have become far more specific when presenting this information in the current literature on treating acute pain conditions with TENS than they were in the literature for the 1978 special issue. Improvement has been made in providing specific details to enable replication of TENS stimulating characteristics among patients with chronic pain; yet several clinical researchers still fail to evaluate treatment outcomes adequately. Perhaps the greatest advances in our understanding of TENS involve the recent development of mechanisms that might account for how different types of TENS work. Suggestions for predicting patient responses to TENS and for avenues of future inquiry are offered. Key Words: Electric stimulation, Pain, Physical therapy. A wealth of information is available on the clinical application of transcutaneous electrical nerve stimulation (TENS) for pain management. In recent years, clinicians have studied the effect of TENS on pain associated with specific pathological conditions and have sought a relationship between specific treatment protocols and outcomes. Authors have more closely attended to the importance of specific electrode placements and stimulation characteristics, so that studies on particular diagnostic groups of patients could be compared and replicated. More sophisticated pain evaluation tools have been used to assess a patient's response to TENS therapy. The purpose of this article is to review critically literature about TENS, which has been generated after the publication of a special issue on TENS in PHYSICAL THERAPY in 1978, to determine if more definitive information is available regarding 1) the efficacy of treatment for specific diagnostic categories, 2) current methods of application (specific elec- Mrs. Gersh is a physical therapist at St. Luke's Memorial Hospital, S 711 Cowley St, Box 288, Spokane, WA 99210. Dr. Wolf is Associate Professor, Department of Rehabilitation Medicine, Emory University School of Medicine, 1441 Clifton Rd, NE, Atlanta, GA 30322 (USA) and a senior investigator, Emory University Rehabilitation Research and Training Center, Atlanta, GA. Address all correspondence to Dr. Wolf. This invited paper was submitted July 16, 1984, and was accepted September 7, 1984. 314 trode placements and stimulation characteristics) and their effects on treatment outcomes, and 3) neurophysiological modes of action. Topics for future clinical study will also be discussed. TRANSCUTANEOUS ELECTRICAL NERVE STIMULATION FOR ACUTE PAIN One of the most successful applications of TENS is for postoperative pain control.1-11 Although treatment protocols vary between different studies, important treatment variables are fairly consistent among these studies.1 Patients are generally provided with a preoperative exposure to TENS to choose comfortable stimulation settings. Sterile electrodes are placed adjacent to the incision in surgery, and TENS treatment commences in the recovery room, with the stimulation variables set at a previously established comfort level. Transcutaneous electrical nerve stimulation is used continuously for the first 48 to 72 hours; the patient regulates the stimulus intensity to suit his needs. Treatment outcomes are measured not only by subjective pain report, but also by the type and amount of pain medication requested by the patient. Incidences of postoperative ileus and atelectasis, records on compliance with respiratory therapy regimens, and length of inten- sive care and hospital stay also provide objective measures of the patient's response to TENS treatment. Schomburg and Carter-Baker evaluated the analgesic effect of TENS on 75 postlaparotomy patients.2 In comparing these patients with a matched control group by retrospective chart observation, the authors found that patients using TENS postoperatively required 56 percent fewer doses of pain medication during the first five postoperative days than did patients in the control group. Patients receiving TENS were more mobile and participated in breathing exercises earlier than their control group counterparts. Ali et al studied the pulmonary function of 40 patients who had undergone cholecystectomies.3 Fifteen patients used TENS continuously for thefirst48 hours postoperatively and then on an "as needed" basis. Another 15 patients did not use TENS, and a third group of 10 patients used TENS units with the batteries reversed so that no current was delivered to the patient (sham TENS). Spirometric evaluations of all patients conducted on the third and fifth postoperative days indicated that patients who were treated with TENS had significantly higher vital capacities and functional residual capacities than patients receiving either sham TENS or no TENS. Patients using TENS had a significantly decreased incidence of postPHYSICAL THERAPY
  • 2. PRACTICE operative pulmonary dysfunction and complications. Patients in all groups required supplemental pain medications, but those patients in the TENS group required less pain medication than did those not receiving actual TENS treatment. Taylor and associates conducted a similar study with patients who had undergone abdominal surgery.4 Thirty patients used actual TENS and 22 patients used sham units for one hour every four hours for the first three postoperative days. Patients were permitted to request pain medication after 30 minutes of TENS treatment if the treatment did not adequately control pain. Twenty-five patients served as a control group. Taylor and associates noted that patients receiving TENS or sham TENS required less pain medication and ambulated earlier than did those patients in the control group.4 The results highlighted the placebo potential of TENS but may also be explained by the noncontinuous mode of TENS application. Another study examined the analgesic effect of TENS on patients who had undergone upper abdominal surgery.6 The patients who used TENS for postoperative pain control required 30 times less pain medication than did those in the control group. Improved pulmonary function, appetite, and ambulation indicated an earlier recovery for those patients who used TENS than for those patients who did not. Because the report of this study lacked information on treatment protocol and technique, replicating or comparing these results with similar studies is impossible. Several investigators have studied the efficacy of TENS for management of postlaminectomy pain.7-9 In all these studies, electrodes were placed parallel to the incision, stimulation was set at comfortable levels, TENS was used continuously for at least the first 24 to 48 hours, and the treatment was discontinued after that period at each patient's request. The investigators all reported a significant decrease in the strength and amount of pain medication requested by the patients using TENS in comparison with those patients not using TENS. Solomon et al reported that TENS appeared most effective in "drugnaive" patients, those who had not used narcotics preoperatively for more than two weeks in the six months before surgery.7 Furthermore, they noted that poor pain relief was reported by drugVolume 65 / Number 3, March 1985 experienced patients, regardless of whether TENS or narcotics were used. This occurrence may suggest a crosstolerance between narcotics and TENS and activation of a similar neural substrate to explain the analgesic effect of both TENS and opioid derivative medications. Richardson and Siquiera carefully recorded the stimulation settings used.8 They observed no correlation between specific pulse widths, rates, or stimulus intensities and the degree of pain relief reported. Other investigators have corroborated this finding.12 Additional benefits of postoperative pain management with TENS may be realized by the postcesarean patient. Nonnarcotic pain control by use of TENS may facilitate earlier mother-infant bonding. Drug-induced side effects such as nausea, drowsiness, and respiratory depression are limited. Narcotics are not passed to the baby by breastfeeding. Pulmonary rehabilitation is facilitated and reduces the occurrence of pulmonary complications in the mother.10 Harvie cited rehabilitation benefits when using TENS to control postoperative pain after knee surgery.11 He studied patients who had undergone total knee replacements, synovectomies, meniscectomies, arthrotomies, patchplasties, or fracture reductions. Electrodes placed over the medial and lateral collateral ligaments provided the most effective pain control. Narcotic use was decreased by 75 to 100 percent. Recovery of quadriceps femoris muscle strength and knee range of motion (ROM) was facilitated. Four of seven patients with total knee replacements achieved 80 to 90 degrees of active knee flexion by the sixth postoperative day; the other three patients achieved the same goal by the eighth postoperative day. Earlier ambulation and decreased length of hospital stay were also reported. Clearly, TENS for management of postoperative knee pain is an important adjunct to a rehabilitation program. Transcutaneous electrical nerve stimulation can also be applied for control of acute dental pain.13, 14 Hansson and Ekblom evaluated 62 patients admitted to an emergency dental clinic with acute pain secondary to pulpal inflammation, apical periodontitis, or postoperative pain after tooth extraction.13 Patients were randomly assigned to one of three groups: those receiving high frequency TENS (100 Hz; n = 22); those receiving low frequency TENS (2 Hz; n = 20); and those receiving a placebo treatment (batteries removed from the unit; n = 20). Electrodes were placed on the face over the painful area. Stimulus intensity was set to three times the sensory threshold for patients in the high frequency group, and three to five times sensory threshold for those receiving low frequency TENS. This latter group experienced muscular contractions associated with the higher intensity. Patients used a visual analog scale to record their pain intensity before, during, and after treatment. Seven of 22 patients (31.8%) in the high frequency group reported pain relief of greater than 50 percent after 30 minutes of treatment, compared with 9 of 20 patients (45%) in the low frequency group, and 2 of 20 (10%) in the placebo group. Pain returned within 10 minutes after treatment in 4 of 7 patients in the high frequency group, and in 2 of 9 patients in the low frequency group. The 2 patients in the placebo group who reported initial relief experienced longer lasting relief. Two other patients in the high frequency group and 2 in the low frequency group reported complete pain relief after treatment. Differences in the analgesic effectiveness of TENS demonstrated between the high and low frequency groups were not significant. The effectiveness of TENS for pain control, however, was significantly greater when either experimental group was compared with the placebo group. Pain control of longer duration might have occurred if treatment duration could have been longer than 30 minutes. Transcutaneous electrical nerve stimulation is being used, especially outside of the United States, to control acute pain associated with labor and delivery.15, 16 Erkola et al evaluated 100 patients who used TENS for pain management during the first stage of labor.15 Electrodes were placed paravertebrally at T10-11 and S2-4. Stimulus intensity was set at a tolerable submotor threshold and regulated by the patient. Thirty-one percent of the patients reported good pain relief, and 55 percent reported moderate relief within one hour of initiating treatment. Details of the pain rating procedure were not described. Patients using TENS, however, requested a similar amount of pain medication during labor in comparison with a control group who did not use TENS. 315
  • 3. Jones reported that 82 percent of the patients in labor using TENS had substantial relief of back labor pain and 71 percent had significant relief of abdominal labor pain during the first stage of labor.16 Again, methods used to measure pain were not described. During the second stage of labor, TENS was frequently discontinued because it interfered with the patient's controlled breathing and pushing efforts. Transcutaneous electrical nerve stimulation also interfered with continuous fetal monitoring. The use of TENS did not affect the length of labor or immediate postnatal health of the infant. Further investigation of the role of TENS in the management of labor pain is warranted with close attention paid to application techniques and measurement of treatment outcome. Reduction of the need for narcotics during labor could contribute to the improved perinatal and postnatal health of the mother and the improved respiratory and neurological status of the newborn child. Methods of application for TENS to control acute pain are summarized in Table 1. All but one report provide specific electrode placements for particular pain locations. Ranges are given most frequently to describe stimulation settings used, and the frequency and duration of TENS treatment is reported. The provision of application details in recent literature allows more accurate comparison and replication of clinical research. Table 2 summarizes the evaluation tools used to assess TENS treatment outcomes for acute pain management. A variety of subjective pain rating scales and recording of pain medication intake were used most commonly to assess the analgesic effect of TENS. In three studies, additional credence was given to favorable treatment outcomes by use of objective physical evaluations, such as pulmonary function studies or joint range-of-motion measurements. In addition to the patients' reports of pain, objective evaluation procedures enhance the reliability and validity of these clinical studies. Recent literature has been favorable on the efficacy of TENS for acute pain control. The location and description of acute pain is usually precise and allows for use of a more specific treatment approach. Homogeneous groups of patients (eg, those with postoperative pain) and matched control groups are readily available for evaluation. Treatment outcomes may be objectively measured in terms of medication intake, respiratory status, rehabilitation factors, and subjective pain ratings. These advantages are not as readily available when studying the management of chronic pain and may explain the wide variation in response to TENS treatment among chronic pain patients. TRANSCUTANEOUS ELECTRICAL NERVE STIMULATION FOR CHRONIC PAIN Studies examining patients with widely divergent diagnoses or symptom complexes are not as prevalent in the TENS literature today as they were several years ago. These studies can provide valuable information in selecting which diagnostic groups of patients respond most favorably to TENS for pain relief. Wolf and colleagues evaluated the responses to TENS of 114 patients with chronic pain.12 Patients reported pain secondary to peripheral neuropathy, peripheral nerve injury, radiculopathy, or musculoskeletal trauma. Electrodes were systematically placed at the painful TABLE 1 Transcutaneous Electrical Nerve Stimulation Application Methods for Acute Pain Primary Author Diagnosis Electrode Placement Pulse Width (µ see) Pulse Rate Intensity (PPS) 0-90 V (comfort) 10-100 Frequency and Duration of Treatments Schomburg2 postlaparotomy parallel to incision 120-340 Ali3 parallel to incision 128-200 10-100 0-135 mA (comfort) Taylor4 Sodipo6 Solomon7 postcholecystectomy postlaparotomy postlaparotomy postoperative constant for first 48 hr, then as needed constant for first 48 hr 80 40 comfort 60 min every 4 hr Richardson8 postlaminectomy parallel to incision parallel to incision 1.0 cm parallel to incision 5 cm parallel to incision Schuster9 postlaminectomy Riley10 Harvie11 postcesarean section postoperative knee pain Hansson13 dental pain 2.5 cm parallel to incision above and below incision over medial and lateral collateral ligaments over painful site constant for first 48 hr 72.5240.0 8.7-240 0.2-38.5 mA 40-100 25-100 0-90 V 250-400 80-100 20-35 mA comfort labor pain Jones16 labor pain 316 paraspinal T10L1, S2-S4 200 100 84 Erkola15 within first 20 hr postoperatively, for 3-12 days constant for first 18-24 hr constant, or 30 min four times a day 2 2-3 times sensory threshold or 3-5 times sensory threshold 20-25 V (comfort) comfort 30 min 30 min during first stage of labor during first stage of labor PHYSICAL THERAPY
  • 4. PRACTICE TABLE 2 Evaluation Methods for Transcutaneous Electrical Nerve Stimulation Treatment for Acute Pain Primary Author Diagnosis Subjective Pain Rating Pain Medication Taken Physical Evaluations Schomburg2 postlaparotomy yes yes Ali3 no yes Taylor4 Sodipo6 Solomon7 Richardson8 postcholecystectomy postlaparotomy postlaparotomy postoperative postlaminectomy yes no yes yes yes yes yes yes none Schuster9 postlaminectomy yes yes none Riley10 postcesarean section postoperative knee pain yes yes none no yes dental pain labor pain labor pain yes yes yes no yes yes Other knee range of motion, straight leg raise, early ambulation none none none Harvie11 Hansson13 Erkola15 Jones 16 site or on related nerve roots or peripheral nerves. Stimulation variables were set to evoke a strong but comfortable sensation in the painful region, and exact electrical settings were recorded. Treatments were conducted on an outpatient basis and were of 30- to 45minute duration. Patients rated their pain intensity on a 10-cm line before, during, and immediately after treatment. In addition, some patients completed the pain descriptor word list found in the McGill Pain Questionnaire.17 Thirteen of 18 patients (72%) with peripheral neuropathy, 6 of 21 patients (28.5%) with peripheral nerve injury, 8 of 36 patients (22%) with radicular pain, and 15 of 39 patients (38.4%) with musculoskeletal pain reported more than 60 percent relief of pain after TENS treatment.12 In the peripheral neuropathy group, patients with postherpetic neuralgia responded most favorably to TENS. Patients with fewer previous analgesic treatments, no surgical intervention, and limited narcotic use responded more favorably than those patients with numerous previous treatments. We found no significant relationship between specific electrode placements or stimulation settings and treatment outcomes, but patients with radiculopathy or peripheral nerve injury responded better to higher intensity stimulation. This observation was also reported by Melzack in treating patients with chronic low back pain.18 Follow- Volume 65 / Number 3, March 1985 spirometry, arterial blood gases pulmonary functions up evaluations on 25 patients who used TENS at home for one month generally indicated decreased benefits from treatment as time progressed. These decreased benefits may have been due to reduced patient compliance when independent TENS application became a requirement. Another investigation studied 98 patients with back pain, headache, or a variety of other pain symptoms.19 Patients used TENS at home, placing electrodes at the site of pain, and setting stimulation intensity at a comfortable level. Patients recorded their own subjective pain level before and after treatment. After 12 days of home treatment, 69 percent of the patients with low back pain, 40 percent of those with headache pain, and 60 percent of those with pain from other sources reported more than 50 percent relief of pain. The authors failed to describe stimulation settings, pain-rating measures, and duration and frequency of treatment; they also did not control for a wide variation in application techniques based on patient competence and compliance. Thus, this study provided little valuable information on TENS for chronic pain control. Santiesteban described the use of low frequency TENS (2-4 Hz) for treatment of spinal pain.20 Stimulus pulse width was set at the maximum for the units used, and intensity was set at 50 mA to evoke a muscle contraction within pain tolerance. Electrodes were placed 2.5 to resumption of activities postoperative complication resume ambulation resume ambulation length of hospital stay postoperative complication 5 cm from the appropriate spinous process in a parallel or crossed configuration. Distal acupuncture points were also stimulated. Patients required less analgesic medication when TENS was used to control pain. Melzack and colleagues recently compared the analgesic effects of TENS and massage in a double-blind study of 41 patients with chronic low back pain.21 Transcutaneous electrical nerve stimulation electrodes were placed in the center of the back and on the lateral thigh. Low frequency stimulation (4-8 Hz) with a strong but tolerable intensity was applied. The massage was performed with a suction cup apparatus. Treatment was given two times a week for 30 minutes, for a maximum of 10 treatments. Treatment outcomes were evaluated using both the present-pain intensity (PPI) scale and the pain-rating index of the McGill Pain Questionnaire.17 Bilateral straight leg raising (SLR) and lumbosacral flexion were also measured. Transcutaneous electrical nerve stimulation produced a significantly greater improvement than massage in the painrating and the PPI scales and in the bilateral SLR measures for these patients.21 Transcutaneous electrical nerve stimulation has been used with various degrees of success in the management of arthritic pain. Taylor et al evaluated the effect of TENS on osteoarthritic knee pain.22 Patients used actual TENS or a 317
  • 5. TABLE 3 Transcutaneous Electrical Nerve Stimulation Application Methods for Chronic Pain Primary Author Diagnosis Wolf12 varied Moore19 Electrode Placement Pulse Width (µ sec) Pulse Rate (pps) Intensity Frequency and Duration of Treatments 100 50-100 submotor threshold 30-45 min, 3-5 times a week varied site of pain, related nerve roots, or peripheral nerve varied midrange 10-100 or 1-4 comfort Santiesteban20 spine pain paravertebral maximum 2-4 Melzack21 low back pain osteoarthritis of knee phantom limb pain nonunited fracture center of back and lateral thigh about knee 4-8 motor threshold (50 mA) to tolerance 30-60 min daily or as needed 30-60 min comfort comfort stump or contralateral limb over fracture site in crossed pattern 100 or 2 peripheral neuropa- along nerve trunk at site of pain Taylor22 Winnem27 Kahn29 Gersh24 300 minimum 200 110 sensory threshold (less than 20 mA) 26-28 mA 30 min, 2 times a week 30-60 min as needed 15 min twice a day 30-60 min, 3-4 times a day continuous, 8-10 hr a day thy placebo unit wired to produce various sounds in a well-monitored home program. After two weeks of home treatment, patients were reevaluated and sent home to use the other (TENS or placebo) unit for another two weeks. Patients were evaluated again and permitted to take home the most beneficial unit for one more month of home treatment. Responses to treatment were evaluated by subjective pain rating, ambulation distance, and analgesic medication intake. The actual TENS provided significantly more pain relief than did the placebo unit in both subjective and medication analyses. Patients reported the greatest pain relief while wearing the active TENS unit. Relief frequently lasted for several hours after treatment was completed. Several patients continued to use the TENS at home for several months. They reported decreasing pain relief over time, possibly because of increasing joint deterioration. Transcutaneous electrical nerve stimulation may be an important adjunct in the rehabilitation of arthritic patients, particularly when joint replacement is not possible. In patients with chronic systemic diseases who may be receiving a variety of pharmacologic and therapeutic treatments concurrently, the clinician must be alert, however, to adverse reactions to TENS, as reported by Griffin and McClure.23 318 Patients with a variety of peripheral neuropathic conditions including peripheral neuropathy,24 postherpetic neuralgia, peripheral nerve injury, reflex sympathetic dystrophy,25 and Sudeck's atrophy26 have all responded favorably to TENS treatment. Transcutaneous electrical nerve stimulation has also proven effective in the management of phantom limb pain27 and the distal burning paresthesia associated with Guillain-Barré syndrome.28 Kahn provided radiographic evidence that TENS facilitated callous formation and osseous bridging at sites of nonunited fractures in three patients.29 Transcutaneous electrical nerve stimulation was originally applied to control pain in these patients for nonunited fractures six months after injury. Electrodes were placed in various configurations to "sandwich" the fracture site. Pulse width was set for the longest "on" time, pulse rate was set at the lowest available frequency, and stimulus intensity was set at the sensory threshold. Increased callous formation was noticed on radiographic examination after one month of treatment in one patient and after 10 weeks of treatment in the other two patients. Millea described another unusual application of TENS.30 A 50-year-old patient with an eight-year history of nonoperative abdominal pain and disten- tion was relieved of this discomfort after using TENS for five days. This relief may be attributed to decreased sympathetic tone and increased gastric motility associated with TENS application.31 Owens et al observed local vasodilation and skin temperature increases of 1°C when TENS was applied at the ulnar groove and wrist in seven healthy subjects.31 Such evidence also may explain the mechanism of pain relief in patients with causalgia or reflex sympathetic dystrophy. Consistent sympathetic nervous system responses, however, have not, as yet, been recorded among a variety of patients.25 Table 3 summarizes the application procedures used for chronic pain control with TENS. Significant effort has been made by most investigators in recent years to specify effective electrode placements and stimulating settings. Although specific pulse widths, rates, and intensities are not always cited, most reports provide a description of the sensory or motor responses elicited by TENS during treatment. Treatment duration was usually 30 to 60 minutes, but the frequency of treatment varied with each study. Replication of clinical studies is facilitated when these procedures are described in detail. Perhaps the weakest aspect of the clinical study of TENS for chronic pain control is evaluation of treatment outPHYSICAL THERAPY
  • 6. PRACTICE comes. Table 4 illustrates that most investigators still rely solely on the patient's report of pain to establish the efficacy of TENS treatment. Often, the pain-rating scale used by the patient is not described in detail. The great variety of pain symptoms, locations, previous and concomitant treatments, medications, and psychological components associated with chronic pain make objective evaluation much more difficult than in patients with acute pain. Use of physical measures, such as joint motion, strength, muscle girth, and participation in functional activities, however, would enhance the objective evaluation of the efficacy of TENS for chronic pain control. PREDICTING RESPONSE TO TRANSCUTANEOUS ELECTRICAL NERVE STIMULATION TREATMENT Successful use of TENS for pain control may be increased as more specific patient evaluation and selection criteria are established. Reynolds and associates examined the predictive value of pain questionnaires in selecting patients who would be more likely to respond favorably to TENS treatment.32 Their evaluation indicated that older, retired patients, who had pain of less than one year duration, who had undergone limited or no surgery, and who used nonnarcotic analgesics were more likely to experience pain relief with TENS. Site of injury, sensory deficit, and secondary gain by financial compensation for injury did not affect response to treatment. The pain questionnaire, however, seemed to have less predictive value for TENS than for other treatment regimens. In another study, Johansson et al suggested that patients with neurogenic pain responded more favorably to TENS than did patients with somatogenic or psychogenic pain.33 Patients with pain in the extremities seemed to derive more relief with TENS than patients with axial pain. The patient's age, sex, and pain intensity did not relate to his response to treatment. Richardson and colleagues explained how treatment with TENS could confirm a diagnosis of functional pain compared with organic pain.34 Many patients with suspected functional pain reported increased pain during and after TENS treatment. Pain was relieved with a saline injection in the majority of these patients. Mannheimer compiled a list of factors that hinder, enhance, or restore the effectiveness of TENS for pain control.35 Among those factors that enhance TENS effectiveness are careful, continuous patient evaluation for most effective electrode placement sites and stimulation settings; changing stimulation modes and characteristics; gradually increasing patient tolerance to stronger stimulation in the painful area; elec- trode placement on motor points or superficial aspects of nerves; weaning patients from addictive medications before treatment; and educating the patient in the proper use of the modality for home treatment. Incorporating these selection and treatment criteria into treatment protocols and recording which patients most favorably respond to TENS will increase the successful use of this modality in the future. NEUROPHYSIOLOGICAL MODES OF ACTION Several years ago, the options available to explain the possible neurophysio l o g y mechanisms through which TENS could affect pain perception were limited.36 The prevailing explanation for most pain attenuating interventions cited the spinal gate concept developed by Melzack and Wall in 1965.37 Briefly, this notion took into account existing electrophysiological data from animal experiments that had demonstrated differential effects of collateral axons from large diameter afferent fibers mediating touch and pressure and from small diameter afferent fibers conveying nociceptive input upon interneurons within the substantia gelatinosa (Fig. 1). These interneurons could be facilitated through predominantly large diameter collateral afferent input and inhibited through primarily collateral axons from the small diameter system. In addition, the interneuron was inhibitory onto the TABLE 4 Evaluation Methods for Transcutaneous Electrical Nerve Stimulation Treatment for Chronic Pain Primary Author Diagnosis Subjective Pain Rating Pain Medication Taken Physical Evaluations Wolf12 varied McGill Pain Questionnaire no none Moore19 Santlesteban20 Melzack21 varied spine pain low back pain yes no no yes no Taylor22 osteoarthritis of knee yes yes Winnem27 phantom limb pain nonunited fracture peripheral neuropathy yes no none none straight leg raise, lumbosacral range of motion roentgenogram, ambulation distance none yes no roentgenogram yes no none Other Kahn29 Gersh24 Volume 65 / Number 3, March 1985 McGill Pain Questionnaire resume functional activities 319
  • 7. Periphery Spinal Cord Lamina II & III Spinal Cord Lamina V Fig. 1. Schematic diagram depicting the Melzack-Wall gate theory of pain. Open circles represent facilitator/ synapses; closed circles indicate inhibitory synapses. Abbreviations SG = substantia gelatinosa; T = transmission cells. terminals of both afferent fiber classes. Consequently, when large diameter afferent fiber activation was of greater frequency and intensity than smaller diameter fiber input, the inhibitory interneurons would be activated to presynaptically inhibit transmission centrally from both the noxious and nonnoxious inputs. The gate would be closed. Of course, the opposite effect would predominate if greater transmission occurred through the smaller diameter system. This gating theory was subjected to considerable criticism because it conceptually failed to account for pain relief among a variety of clinical conditions. Nonetheless, the test of time has proven that the framework for the theory has formed the basis for several more contemporary explanations of pain alleviation through TENS. Specifically what the Melzack-Wall model brought to the attention of scientists and clinicians was the recognition that pain perception could be modulated somewhere within the neuraxis if the appropriate stimuli could be delivered and the appropriate neural substrate on which such stimuli might act could be found. A spinal gate that conceptually follows the original model might incorporate conventional TENS (low intensity, high frequency stimuli) to effect pain reduction among patients with a diagnosis of postherpetic neuralgia. This disease process causes selective degeneration among large diameter peripheral axons. The success with conventional TENS may reside in the activation of 320 remaining large afferent fibers or those in close proximity to the painful site but which enter the neuraxis at the same or nearby segments as the ongoing noxious input.38 A similar explanation may be appropriate to explain how pain following certain kinds of peripheral nerve injury may respond to conventional TENS.39 Recently, clinicians have recognized that conventional TENS may not be the most effective form of stimulation for certain types of chronic pain. This thought was promoted when Ericksson and co-workers identified a large group of patients with chronic pain who showed further improvement in reduced pain perception when conventional TENS was supplemented by acupuncture-like TENS (low frequency, high intensity stimulation).40 This latter form of stimulation showed effects that were reversible through the administration of the opioid antagonist, naloxone hydrochloride; this reversal suggests that the effects of acupuncture-like TENS might be mediated through an endogenous opiate system within the neuraxis.41 Previously, Mayer and colleagues had demonstrated that the effectiveness of acupuncture was also reversed by naloxone hydrochloride.42 These clinical findings prompted a comprehensive search for the neural substrates mediating the responsiveness of chronic pain patients to high intensity cutaneous stimulation. At the same time, a variety of opiate receptors and numerous loci of endogenous opiates were being discovered in many human and subhuman primate studies.43 A logical marriage from this exponentially increasing body of knowledge resided in establishing relationships between neurophysiological and neurohistochemical studies on pain mechanisms and opiate substances, respectively. The mechanismfirstproposed by Basbaum and Fields in 1978 served to collate known histochemical and physiological data to explain how high intensity cutaneous electrical stimulation (for example, acupuncture-like TENS, briefintense TENS, or burst trains of TENS) might activate endogenous opiates to alleviate pain.44 This modulatory mechanism is essentially a negative feedback loop that is schematically illustrated in Figure 2. Ongoing pain input and the discomfort often associated with high intensity TENS activate ascending pathways leading to conscious awareness of pain. Certain axons within the ascending system are known to form a synapse within medullary reticular formation nuclei, and from these nuclei, this input is transmitted to the periaqueductal gray region of the midbrain (mesencephalon). This location is exceptionally endowed with high concentrations of endogenous opiates, and when it is activated, either through natural cutaneous Central Nervous System Fig. 2. Schematic diagram of negative feedback loop within the neuraxis activated by noxious input. PHYSICAL THERAPY
  • 8. PRACTICE stimulation, iontophoretically applied morphine, or through direct stimulation, its efferent axons form a synapse with nuclei (raphe magnus and reticularis magnocellularis) within the medulla oblongata. Output from these nuclear groups descends through the dorsolateral funiculus of the spinal cord to make enkephalinergic synapses known to inhibit the spinal transmission of Substance P, a polypeptide implicated as a neurotransmitter between axons conveying noxious information.45 This last neural interaction completes the negative feedback loop to modulate ongoing or subsequent noxious input. For further details, please refer to the Pain: Mechanism: B. Basic section within the Bibliography. Another mechanism that may account for some aspects of pain modulation with TENS involves what LeBars et al have termed "diffuse noxious inhibitory controls," or DNIC.46 Within this system, responses elicited through continuous pain input to convergent dorsal horn neurons may be suppressed effectively by noxious or intense cutaneous stimulation, when it is applied almost anywhere on the body surface. Responses obtained through activity within the small diameter afferent fiber groups are inhibited, but nonnoxious activation of the same convergent cells or nonconvergent cells responsive to only noxious stimuli remain unaffected. Within animal models, spinalization eliminates DNIC, thereby suggesting that descending supraspinal influences are required to activate this system. Furthermore, the DNIC mechanism is sensitive to naloxone hydrochloride; this sensitivity indicates an endorphin link.47 Whether this linkage occurs at spinal or supraspinal levels has yet to be determined. Also, definitive data to test the validity of the DNIC model in man have yet to be presented. Nonetheless, the mechanisms described in this article form plausible explanations for the way in which high intensity TENS might modulate pain perception. Other mechanisms have been proposed, but both the quantity and quality of research led us to refrain from addressing these in this article. Undoubtedly, as more data evolve and histochemical and electrophysiological techniques gain sophistication, additional ways of speculating on or comprehending how TENS modulates pain perception will be forthcoming. Volume 65 / Number 3, March 1985 AREAS FOR FUTURE STUDY To facilitate the continued effective use of TENS for pain control, several areas of study must be pursued. Patient evaluation and selection criteria should be validated and refined to increase successful treatment with TENS, particularly in patients who have chronic pain. Specific electrode placements and stimulation characteristics must be evaluated in relation to specific disease entities to establish more effective treatment protocols. Clinicians should continue to evaluate the benefits of high versus low frequency stimulation, auriculotherapy,48 and acupuncture point stimulation. Use of TENS for acute pain control should be expanded within areas where it is apparently effective (eg, postoperative pain, labor and delivery pain, and pain from acute injury48). Adverse responses to treatment such as contact dermatitis49, 50 should be reported so that hypoallergenic materials can be developed in the manufacturing of electrodes and conductive media, and so that patients at high risk for negative responses to treatment may be screened.23 Ongoing evaluation of long-term use of TENS by chronic pain patients may yield information on long-term effectiveness and clarify the neurophysiology on which treatment is based. The expanding body of knowledge resulting from applied and basic research on neurochemical and physiological bases for pain control must address the modus operandi of TENS, taking into account the stimulus characteristics applied within experimental protocols and how the relationship between stimulation and response explains the efficacy of this modality. REFERENCES 1. Santiesteban AJ, Sanders BR: Establishing a postsurgical TENS program. Phys Ther 60:789-791, 1980 2. Schomburg FL, Carter-Baker SA: Transcutaneous electrical nerve stimulation for postlaparotomy pain. Phys Ther 63:188-193, 1983 3. Ali J, Yaffe CS, Serrette C: The effect of transcutaneous electrical nerve stimulation on postoperative pain and pulmonary function. Surgery 89:507-512, 1981 4. Taylor AG, West BA, Simon B, et al: How effective is TENS for acute pain? Am J Nurs 83:1171-1174, 1983 5. Bussey JG, Jackson A: TENS for Postsurgical Analgesia. 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Melzack R, Vetere P, Finch L: Transcutaneous electrical nerve stimulation for low back pain: A comparison of TENS and massage for pain and range of motion. Phys Ther 63:489-493, 1983 22. Taylor P, Hallett M, Flaherty L: Treatment of osteoarthritis of the knee with transcutaneous electrical nerve stimulation. Pain 11:233-240, 1981 23. Griffin JW, McClure M: Adverse reactions to transcutaneous electrical nerve stimulation in a patient with rheumatoid arthritis. Phys Ther 61:354-355,1981 24. Gersh MR, Wolf SL, Rao VR: Evaluation of transcutaneous electrical nerve stimulation for pain relief in peripheral neuropathy: A clinical documentation. Phys Ther 60:48-52,1980 25. Meyerson BA: Electrostimulation procedures, effects, presumed rationale and possible mechanisms. Advances in Pain Research and Therapy 5:495-534, 1983 26. Bodenheim R, Bennett JH: Reversal of a Sudeck's atrophy by the adjunctive use of transcutaneous electrical nerve stimulation: A case report. 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  • 9. 29. Kahn J: Transcutaneous electrical nerve stim­ ulation for nonunited fractures: A clinical re­ port. Phys Ther 62:840-844, 1982 30. Millea TP: Transcutaneous electrical nerve stimulation in the management of nonoperative intra-abdominal pain: A case report. Phys Ther 63:1280-1282, 1983 31. Owens S, Atkinson ER, Lees DE: Thermo­ graphic evidence of reduced sympathetic tone with transcutaneous nerve stimulation. Anes­ thesiology 50:62-65, 1979 32. Reynolds AC, Abram SE, Anderson RA, et al: Chronic pain therapy with TENS: Predictive value of questionnaires. Arch Phys Med Rehabil 64:311-313, 1983 33. Johansson F, Almay BGL, Von Knorring L, et al: Predictors for the outcome of treatment with high frequency transcutaneous electrical nerve stimulation in patients with chronic pain. Pain 9:55-61, 1980 34. Richardson RR, Arbit J, Siquiera EB, et al: Transcutaneous electrical neurostimulation in functional pain. Spine 6:185-188,1981 35. 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Brain Res 173:295301,1979 Mayer DJ, Price DD, Rafii A: Antagonism of acupuncture analgesia in man by the narcotic antagonic naloxone. Brain Res 121:368-372, 1977 43. Olson GA, Olson RD, Kastin AJ, et al: Endog­ enous opiates: 1981. Peptides (Fayetteville) 3:1039-1073 44. Basbaum Al, Fields HL: Endogenous pain con­ trol mechanisms: Review and hypothesis. Ann Neurol 4:451-462, 1978 45. Basbaum Al: The generation and control of pain. In Grossman RG, et al (eds): The Clinical Neurosciences. New York, NY, Churchill Liv­ ingstone Inc. 1983, vol 5, pp 301-324 46. LeBars D, Dickenson AH, Besson JM: Diffuse noxious inhibitory control (DNIC): I. Effects on dorsal horn convergent neurons in the rat. Pain 6:283-304, 1979 47. LeBars D, Chibour D, Kraus E, et al: Effect of naloxone upon diffuse noxious inhibitory con­ trols (DNIC) in the rat. Brain Res 204:387-402, 1981 48. Paris DL, Baynes F, Gucker B: Effects of the Neuroprobe in the treatment of second-degree ankle inversion sprains. Phys Ther 63:35-40, 1983 49. Bolton L: TENS electrode irritation. J Am Acad Dermatol 8:134-135, 1983 50. Zugenman C: Dermatitis from TENS. J Am Acad Dermatol 6:936-939,1982 BIBLIOGRAPHY PAIN: TENS 1. Abram SE, Reynolds AC, Cusick FJ: Failure of naloxone to reverse analgesia from transcutaneous electrical stimula­ tion in patients with chronic pain. Anesth Analg 60:81-84, 1981 2. Berlant SR: Method of determining op­ timal stimulation sites for transcutaneous electrical nerve stimulation. Phys Ther 64:924-928, 1984 3. Besson JM, Chitour D, Dickenson AH, et al: Involvement of endogenous opiates in diffuse noxious inhibitory controls. J Physiol (Lond) 300:26, 1980 4. Bodenheim R, Bennett JH: Reversal of a Sudeck's atrophy by the adjunctive use of transcutaneous electrical nerve stimulation: A case report. Phys Ther 63:1287-1288,1983 5. Bohm E: Transcutaneous electrical nerve stimulation in chronic pain after peripheral nerve injury. Acta Neurochir (Wien) 40:277-283, 1978 6. Butikofer R, Lawrence PD: Electrocutaneous nerve stimulation—II: Stimulus waveform selection. IEEE Trans Biomed Eng 26:69-75, 1979 7. Chung JM, Fang ZR, Cargill CL, et al: Prolonged, naloxone-reversible inhibition of the flexion reflex in the cat. Pain 15:35-53,1983 8. Doliber CM: Role of the physical thera­ pist at pain treatment centers: A Survey. Phys Ther 64:905-909, 1984 9. Fried T, Johnson R, McCracken W: Transcutaneous electrical nerve stimu­ 322 10. 11. 12. 13. 14. 15. 16. 17. 18. lation: Its role in the control of chronic pain. Arch Phys Med Rehabil 65:228231,1984 Goldner JL, Nashold BS Jr, Hendrix PC: Peripheral nerve electrical stimulation. Clin Orthop 163:33-41, 1982 Hansson P, Ekblom A: Transcutaneous electrical nerve stimulation (TENS) as compared to placebo TENS for the relief of acute oro-facial pain. Pain 15:157165,1983 Harvie KW: A major advance in the con­ trol of postoperative knee pain. Or­ thopedics 2:1-2, 1979 Hiedl P, Struppler A, Gessler M: TENSevoked long loop effects. Appl Neurophysiol 42:153-159, 1979 Hughes GS Jr, Lichstein PR, Whitlock D, et al: Response of plasma beta-endorphins to transcutaneous electrical nerve stimulation in healthy subjects. Phys Ther 64:1062-1066,1984 Ignelzi RJ, Nyquist JK: Excitability changes in peripheral nerve fibers follow­ ing repetitive electrical stimulation: Impli­ cations in pain modulation. J Neurosurg 51:824-830,1979 Janko M, Trontelj JV: Transcutaneous electrical nerve stimulation: A microneurographic and perceptual study. Pain 9:219-230, 1980 Janko M, Trontelj JV: Flexion withdrawal reflex as recorded from single human biceps femoris motor neurones. Pain 15:167-176,1983 Jenkner FL, Schurfried F: Transdermal transcutaneous electric nerve stimula­ tion for pain: The search for an optimal waveform. Appl Neurophysiol 44:330337, 1981 19. Johansson F, Almay BGL, Von Knorring L, et al: Predictors for the outcome of treatment with high frequency transcu­ taneous electrical nerve stimulation in patients with chronic pain. Pain 9:55-61, 1980 20. Krueger HC, Wong R, Jette DU: Opin­ ions and comments: Use or misuse of TENS with acupuncture. Phys Ther 64:1574-1576,1984 21. LeBars D, Besson JM: The spinal site of action of morphine in pain relief: From basic research to clinical applications. Trends in Pharmacological Sciences 2:323-325, 1981 22. Lewis JW, Cannon JT, Lieberskind JC: Opioid and nonopioid mechanisms of stress analgesia. Science 208:623-625, 1980 23. Malow RM, Dougher MJ: A signal detec­ tion analysis of the effects of transcuta­ neous stimulation on pain. Psychosom Med 41:101-108, 1979 24. Mannheimer C, Lund S, Carlsson C-A: The effect of transcutaneous electrical nerve stimulation (TENS) on joint pain in patients with rheumatoid arthritis. Scand J Rheumatol 7:13-16, 1978 25. Martin R, Salbaing J, Blaise G, et al: Epidural morphine for postoperative pain relief: A dose-response curve. J Anes­ thesiology 56:423-426, 1982 26. McCarthy JA, Zigenfus RW: Transcuta­ neous electrical nerve stimulation: An ad­ junct in the pain management of GuillainBarre Syndrome: A case report. Phys Ther 58:23-24,1978 PHYSICAL THERAPY
  • 10. PRACTICE 27. McCreery DB, Bloedel JR: A critical ex­ amination of the use of signal detection theory in evaluating a putative analge­ sic—transcutaneous electrical nerve stimulation. Sensory Processes 2:3857, 1978 28. Melzack R: Recent concepts of pain. J Med 13:147-160, 1982 29. Melzack R, Vetere P, Finch L: Transcu­ taneous electrical nerve stimulation for low back pain: A comparison of TENS and massage for pain and range of mo­ tion. Phys Ther 63:489-493, 1983 30. Meyer PG, Nashold BS, Peterson J: Di­ agnosis of electric neurostimulating de­ vice dysfunction. Appl Neurophysiol 42:352-364, 1979 31. Millea TP: Transcutaneous electrical nerve stimulation in the management of nonoperative intra-abdominal pain: A case report. Phys Ther 63:1280-1282, 1983 32. Miller Jones CMH: Forum: Transcuta­ neous nerve stimulation in labour. An­ aesthesia 35:372-375, 1980 33. Nielźen S, Sjölund BH, Eriksson MBE: Psychiatric factors influencing the treat­ ment of pain with peripheral conditioning stimulation. Pain 13:365-371, 1982 34. O'Brien WJ, Rutan FM, Sanborn C, et al: Effect of transcutaneous electrical nerve stimulation on human blood β-en­ dorphin levels. Phys Ther 64:13671374, 1984 35. Ottoson D, Ekblom A, Hansson P: Vibra­ tory stimulation for the relief of pain of dental origin. Pain 10:37-45, 1981 36. Owens S, Atkinson ER, Lees DE: Ther­ mographic evidence of reduced sympa­ thetic tone with transcutaneous nerve stimulation. Anesthesiology 50:62-65, 1979 37. Paris DL, Baynes F, Gucker B: Effects of the neuroprobe in the treatment of second-degree ankle inversion sprains. Phys Ther 63:35-40, 1983 38. Pesschanski M, Guilbaud G, Gautron M: Posterior intralaminar region in rat: Neu­ ronal responses to noxious and nonnoxious cutaneous stimuli. Exp Neurol 73:226-238, 1981 39. Pike PMH: Transcutaneous electrical stimulation: Its use in the management of postoperative pain. Anaesthesia 33:165-171, 1978 40. Pomeranz B, Cheng R: Suppression of noxious responses in single neurons of cat spinal cord by electroacupuncture and its reversal by the opiate antagonist naloxone. Exp Neurol 64:327-341, 1979 41. Reynolds AC, Abram SE, Anderson RA, et al: Chronic pain therapy with transcu­ taneous electrical nerve stimulation: Pre­ dictive value of questionnaires. Arch Phys Med Rehabil 64:311-313, 1983 42. Richardson RR, Cerullo LJ: Transab­ dominal neurostimulation in treatment of neurogenic ileus. Appl Neurophysiol 42:375-382, 1979 43. Richardson RR, Cerullo LJ, Raimondi AJ: Transabdominal neurostimulation in the treatment of neurogenic ileus. Paper read at Fifty-fifth Annual American Con­ gress of Rehabilitation Medicine, New Orleans, LA, November 12, 1978 Volume 65 / Number 3, March 1985 44. Salar G, Job I: Modification de L'Action Antalgioue de L'Electrotérapie Transcutanee Aprés Traitement Avec Naloxone: Note préliminaire. Neurochirurgie 24:415-417,1978 45. Salar G, Job I, Mingrino S, et al: Effect of transcutaneous electrotherapy on CSF beta-endorphin content in patients without pain problems. Pain 10:169- 172, 1981 46. Schneider RJ: Low temperature painful stimulus alters brain wave pattern of transcutaneous electrical stimulus. Life Sci 28:1269-1278, 1981 47. Schomburg FL, Carter-Baker SA: Transcutaneous electrical nerve stimulation for postlaparotomy pain. Phys Ther 63:188193, 1983 48. Sebille A, Bondoux-Jahan M: Effects of electric stimulation and previous nerve injury on motor function recovery in rats. Brain Res 193:562-565, 1980 49. Siegfried J, Haas HL: Inhibition by transcutaneous electrical stimulation of noxious heat elicited in human gasserian ganglion. Eur Neurol 18:353-355, 1979 50. Stanley TH, Cazalaa JA, Atinault A, et al: Transcutaneous cranial electrical stimulation decreases narcotic requirements during neurolept anesthesia and operation in man. Anesth Analg 61:863- 866, 1982 51. Stanley TH, Cazalaa JA, Limoge A, et al: Transcutaneous cranial electrical stimulation increases the potency of nitrous oxide in humans. Anesthesiology 57:293-297, 1982 52. Strax TE (Instructor): TENS-clinical applications. Paper read at the Fifty-fifth Annual American Congress of Rehabilitation Medicine, New Orleans, LA, November 14, 1978 53. Talonen P, Malmivuo J, Baer G, et al: Transcutaneous, dual channel phrenic nerve stimulator for diaphragm pacing. Med Biol Eng Comput 21:21-30, 1983 54. Taylor P, Hallett M, Flaherty L: Treatment of osteoarthritis of the knee with transcutaneous electrical nerve stimulation. Pain 11:233-240, 1981 55. Trief PM: Chronic back pain: Tripartite model of outcome. Arch Phys Med Rehabil 64:53-56, 1983 56. Urban BJ, Nashold BS: Combined epidural and peripheral nerve stimulation for relief of pain. J Neurosurg 57:365-369, 1982 57. Wilier JC, Roby A, Boulu P, et al: Depressive effect of high frequency peripheral conditioning stimulation upon the nociceptive component of the human blink reflex: Lack of naloxone effect. Brain Res 239:322-326, 1982 58. Wilier JC, Roby A, Boulu P, et al: Comparative effects of electroacupuncture and transcutaneous nerve stimulation on the human blink reflex. Pain 14:267-278, 1982 59. Wolf SL, Gersh MR, Rao VR: Examination of electrode placements and stimulating parameters in treating chronic pain with conventional transcutaneous electrical nerve stimulation (TENS). Pain 11:37-47,1981 60. Wong RA, Jette DU: Changes in sympathetic tone associated with different forms of transcutaneous electrical stimulation in healthy subjects. Phys Ther 64:478-482, 1984 61. Woolf CJ: Transcutaneous electrical nerve stimulation and the reaction to experimental pain in human subjects. Pain 7:115-127,1979 62. Woolf CJ, Barrett GD, Mitchell D, et al: Naloxone-reversible peripheral electroanalgesia in intact and spinal rats. Eur J Pharmacol 45:311-314,1977 63. Wynne J, Parry L: Transcutaneous nerve stimulation—an experimental study of its analgesic action. Acupunct Electrother Res 4:195-202, 1979 64. Zoppi M, Francini F, Maresca C, et al: Changes of cutaneous sensory thresholds induced by non-painful transcutaneous electrical nerve stimulation in normal subjects and in subjects with chronic pain. J Neurol Neurosurg Psychiatry 44:708-717,1981 PAIN: MECHANISM A. Clinical 1. Abram SE, Anderson RA: Using a pain questionnaire to predict response to steroid epidurals. Reg Anaesth 5:1114,1980 2. Abram SE, Anderson RA, MaitraD'Cruze AM: Factors predicting shortterm outcome of nerve blocks in the management of chronic pain. Pain 10:323-330,1981 3. Amano K, Tanikawa T, Kawamura H, et al: Endorphins and pain relief—further observations on electrical stimulation of the lateral part of the periaqueductal gray matter during rostral mesencephalic reticulotomy for pain relief. Appl Neurophysiol 45:123-135, 1982 4. Besson JM, Guilbaud G, Abdelmoumene M, et al: Physiologie de la nociception. J Physiol (Paris) 78:7-107, 1982 5. Boivie J, Meyerson BA: A correlative anatomical and clinical study of pain suppression by deep brain stimulation. Pain 13:113-126, 1982 6. Brucini M, Duranti R, Galletti R, et al: Pain thresholds and electromyographic features of periarticular muscles in patients with osteoarthritis of the knee. Pain 10:57-66, 1981 7. Campbell JN: Examination of possible mechanisms by which stimulation of the spinal cord in man relieves pain. Appl Neurophysiol 44:181-186,1981 8. Chao EYS: Justification of triaxial goniometer for the measurement of joint rotation. J Biomech 13:989-1006, 1980 9. Clum GA, Luscumb RL, Scott L: Relaxation training and cognitive redirection strategies in the treatment of acute pain. Pain 12:175-183, 1982 10. Condes- Lara M, Calvo JM, FernandezGuardiola A: Habituation to bearable experimental pain elicited by tooth pulp electrical stimulation. Pain 11:185-200, 1981 323
  • 11. 11. Cram JR, Stegar JC: EMG scanning in the diagnosis of chronic pain. Biofeedback Self Regul 8:229-241, 1983 12. Doleys DM, Crocker M, Patton D: Response of patients with chronic pain to exercise quotas. Phys Ther 62:11111114,1982 13. Dowling J: Autonomic indices and reactive pain reports on the McGill Pain Questionnaire. Pain 14:387-392, 1982 14. Duranti R, Galletti R, Pantaleo T: Relationships between characteristics of electrical stimulation, muscle pain and blink responses in man. Electroencephalogr Clin Neurophysiol 55:637-644, 1983 15. Gehrig JD, Colpitts YH, Chapman CR: Effects of local anesthetic infiltration on brain potentials evoked by painful dental stimulation. Anesth Analg 60:779782, 1981 16. Gregg JM, Banerjee T, Ghia JN, et al: Radiofrequency thermoneurolysis of peripheral nerves for control of trigeminal neuralgia. Pain 5:231-243, 1978 17. Hiedl P, Struppler A, Gessler M: Local analgesia by percutaneous electrical stimulation of sensory nerves. Pain 7:129-134,1979 18. Hosobuchi Y: The majority of unmyelinated afferent axons in human ventral roots probably conduct pain. Pain 8:167-180,1980 19. Howe JF: Phantom limb pain—a reafferentation syndrome. Pain 15:101107, 1983 20. Kaplan RM, Metzger G, Jablecki C: Brief cognitive and relaxation training increases tolerance for a painful clinical electromyographic examination. Psychosom Med 45:155-162, 1983 21. King RB: Principles of pain management: A short review. J Neurosurg 50:554-559, 1979 22. Krivoy WA, Couch JR, Stewart JM, et al: Modulation of cat monosynaptic reflexes by substance P. Brain Res 202:365-372, 1980 23. Laemle LK: Neuronal populations of the human periaqueductal gray, nucleus lateralis. J Comp Neurol 186:93-107, 1979 24. Laitinen LV: Inhibition of cutaneous nociception by deep musculoskeletal pain: A clinical observation. Pain 13:373-377, 1982 25. Levine JD, Gordon NC, Fields HL: Naloxone dose dependently produces analgesia and hyperalgesia in postoperative pain. Nature 278:740-741, 1979 26. Levine JD, Gordon NC, Smith R, et al: Post-operative pain: Effect of extent of injury and attention. Brain Res 234:500-504, 1982 27. Levine JD, Lane ST, Gordon NC, et al: A spinal opioid synapse mediates the interaction of spinal and brain stem sites in morphine analgesia. Brain Res 236:85-91,1982 28. Lindblom U, Tegner R: Are the endorphins active in clinical pain states? Narcotic antagonism in chronic pain patients. Pain 7:65-68, 1979 29. Long DM, Erickson D, Campbell J, et al: Electrical stimulation of the spinal cord and peripheral nerves for pain con- 324 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. trol. Appl Neurophysiol 44:207-217, 1981 Malow RM, Olson RE: Changes in pain perception after treatment for chronic pain. Pain 11:65-72, 1981 Markoff RA, Ryan P, Young T: Endorphins and mood changes in long-distance running. Med Sci Sports Exerc 14:11-15,1982 Marsland AR, Weekes JWN, Atkinson RL, et al: Phantom limb pain: A case for beta blockers? Pain 12:295-297, 1982 Mather L, Mackie J: The incidence of postoperative pain in children. Pain 15:271-282,1983 Meglio M, Cioni B, Del Lago A, et al: Pain control and improvement of peripheral blood flow following epidural spinal cord stimulation. J Neurosurg 54:821-823, 1981 Melzack R, Loeser JD: Phantom body pain in paraplegics: Evidence for a central "Pattern Generating Mechanism" for pain. Pain 4:195-210, 1978 Meyer RA, Campbell JN: Myelinated nociceptive afferents account for the hyperalgesia that follows a burn to the hand. Science 213:1527-1529, 1981 Mills KR, Newham DJ, Edwards RHT: Force, contraction frequency and energy metabolism as determinants of ischaemic muscle pain. Pain 14:149154, 1982 Neumann PB, Henriksen H, Grosman N, et al: Plasma morphine concentrations during chronic oral administration in patients with cancer pain. Pain 13:247-252, 1982 Noordenbos W, Wall PD: Implications of the failure of nerve resection and graft to cure chronic pain produced by nerve lesions. J Neurol Neurosurg Psychiatry 44:1068-1073, 1981 Pertovaara A, Kemppainen P, Johansson G, et al: Ischemic pain nonsegmentally produces a predominant reduction of pain and thermal sensitivity in man: A selective role for endogenous opioids. Brain Res 251:83-92, 1982 Pertovaara A: Modification of human pain threshold by specific tactile receptors. Acta Physiol Scand 107:339-341, 1979 Ray CD: Spinal epidural electrical stimulation for pain control: Practical details and results. Appl Neurophysiol 44:194- 206, 1981 43. Ready LB, Sarkis E, Turner JA: Selfreported vs actual use of medications in chronic pain patients. Pain 12:285- 294, 1982 44. Richelson E: Spinal opiate administration for chronic pain: A major advance in therapy. Mayo Clin Proc 56:1-3, 1981 45. Roby A, Bussel B, Wilier JC: Morphine reinforces post-discharge inhibition of a-motoneurons in man. Brain Res 222:209-212, 1981 46. Rosenfeld JP, Pickrel C, Bronton JG: Analgesia for orofacial nociception produced by morphine microinjection into the spinal trigeminal complex. Pain 15:145-155, 1983 47. Salter M, Brooke RI, Merskey H, et al: Is the temporo-mandibular pain and dysfunction syndrome a disorder of the mind? Pain 17:151-166, 1983 48. Schull J, Kaplan H: Naloxone can alter experimental pain and mood in humans. Physiological Psychology 9:245-250, 1981 49. Scott DS, Gregg JM: Myofascial pain of the temporo-mandibular joint: A review of the behavioral-relaxation therapies. Pain 9:231-241, 1980 50. Simone DA, Bodnar RJ: Modulation of antinociceptive responses following tail pinch stress. Life Sci 30:719-729, 1982 51. Speculand B, Goss AN, Hughes A, et al: Temporo-mandibular joint dysfunction: Pain and illness behavior. Pain 17:139-150,1983 52. Turner JA, Calsyn DA, Fordyce WE, et al: Drug utilization patterns in chronic pain patients. Pain 12:357-363, 1982 53. Varni JW: Self-regulation techniques in the management of chronic arthritic pain in hemophilia. Behavior Therapy 12:185-194, 1981 54. Varni JW: Behavioral medicine in hemophilia arthritic pain management: Two case studies. Arch Phys Med Rehabil 62:183-187, 1981 55. Varni JW, Bessman CA, Russo DC, et al: Behavioral management of chronic pain in children: Case study. Arch Phys Med Rehabil 61:375-379, 1980 56. Wilier JC, Albe-Fessard D: Further studies on the role of afferent input from relatively large diameter fibers in transmission of nociceptive messages in humans. Brain Res 278:318-321, 1983 57. Wilier JC, Boureau F, Albe-Fessard D: Human nociceptive reactions of spatial summation of afferent input from relatively large diameter fibers. Brain Res 201:465-470, 1980 58. Wilier JC, Boureau F, Albe-Fessard D: Supraspinal influences on nociceptive flexion reflex and pain sensation in man. Brain Res 179:61-68, 1979 59. Wolf SL: Perspectives on central nervous system responsiveness to transcutaneous electrical nerve stimulation. Phys Ther 58:1443-1449, 1978 60. Woolf CJ: Evidence for a central component of post-injury pain hypersensitivity. Nature 306:686-688, 1983 PAIN: MECHANISM B. Basic 1. Abbott FV, Melzack R, Samuel C: Morphine analgesia in the tail-flick and formalin pain tests is mediated by different neural systems. Exp Neurol 75:644651,1982 2. Abols IA, Basbaum AI:Afferent connections of the rostral medulla of the cat: A neural substrate for midbrain-medullary interactions in the modulation of pain. J Comp Neurol 201:285-297, 1981 3. Andersen E, Nachum D: An ascending serotonergic pain modulation pathway from the dorsal raphe nucleus to the PHYSICAL THERAPY
  • 12. PRACTICE 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. parafasciculans nucleus of the thalamus. Brain Res 269:57-67, 1983 Andersen RK, Lund JP, Puil E: Excitation and inhibition of neurons in the trigeminal nucleus caudalis following periaqueductal gray stimulation. Can J Physiol Pharmacol 56:157-161, 1978 Azami J, Llewelyn MB, Roberts MHT: The contribution of nucleus reticularis paragigantocellularis and nucleus raphe magnus to the analgesia produced by systemically administered morphine, investigated with the microinjection technique. Pain 12:229246, 1982 Basbaum Al, Clanton CH, Fields HL: Three bulbospinal pathways from the rostral medulla of the cat: An autoradiographic study of pain modulating systems. J Comp Neurol 178:209-224, 1978 Basbaum Al, Fields HL: Endogenous pain control mechanisms: Review and hypothesis. Ann Neurol 4:451-462, 1978 Beal JA, Bicknell HR: Primary afferent distribution pattern in the marginal zone (Lamina I) of adult monkey and cat lumbosacral spinal cord. J Compar Neurol 202:255-263, 1981 Beal JA, Penny JE, Bicknell HR: Structural diversity of marginal (Lamina I) neurons in the adult monkey (Macaca mulatta) lumbosacral spinal cord: A Golgi study. J Compar Neurol 202:237-254, 1981 Behbehani MM, Fields HL: Evidence that an excitatory connection between the periaqueductal gray and nucleus raphe magnus mediates stimulation produced analgesia. Brain Res 170:8593,1979 Behbehani MM, Pomeroy SL: Effect of morphine injected in periaqueductal gray on the activity of single units in nucleus raphe magnus of the rat. Brain Res 149:266-269, 1978 Benabid AL, Henriken SJ, McGinty JF, et al: Thalamic nucleus ventro-posterolateralis inhibits nucleus parafasciculans response to noxious stimuli through a non-opioid pathway. Brain Res 280:217-231, 1983 Bennett GJ, Mayer DJ: Inhibition of spinal cord interneurons by narcotic microinjection and focal electrical stimulation in the periaqueductal central gray matter. Brain Res 172:243-257, 1979 Biedenbach MA, Van Hassel HJ, Brown AC: Tooth pulp-driven neurons in somatosensory cortex of primates: Role in pain mechanisms including a review of the literature. Pain 7:31-50, 1979 Brinkhus HB, Carstens E, Zimmermann M: Encoding of graded noxious skin heating by neurons in posterior thalamus and adjacent areas in the cat. Neurosci Lett 15:37-42, 1979 Brinkhus HB, Zimmermann M: Characteristics of spinal dorsal horn neurons after partial chronic deafferentation by dorsal root transection. Pain 15:221-236, 1983 Brushart TM, Henry EW, Mesulam MM: Reorganization of muscle afferent projections accompanies peripheral Volume 65 / Number 3, March 1985 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. nerve regeneration. Neuroscience 6:2053-2061,1981 Burgoin S, Oliveras JL, Bruxelle J, et al: Electrical stimulation of the nucleus raphe magnus in the rat. Effects on 5HT metabolism in the spinal cord. Brain Res 194:377-389, 1980 Cannon JT, Lewis JW, Weinberg VE, et al: Evidence for the independence of brainstem mechanisms mediating analgesia induced by morphine and two forms of stress. Brain Res 269:231236, 1983 Cannon JT, Prieto GJ, Lee A, et al: Evidence for opioid and non-opioid forms of stimulation-produced analgesia in the rat. Brain Res 243:315-321, 1982 Carstens E: Inhibition of spinal dorsal horn neuronal responses to noxious skin heating by medial hypothalamic stimulation in the cat. J Neurophysiol 48:808-822, 1982 Carstens E, Fraunhoffer M, Suberg SN: Inhibition of spinal dorsal horn neuronal responses to noxious skin heating by lateral hypothalamic stimulation in the cat. J Neurophysiol 50:192-204, 1983 Carstens E, Fraunhoffer M, Zimmermann M: Serotonergic mediation of descending inhibition from midbrain periaqueductal gray, but not reticular formation, of spinal nociceptive transmission in the cat. Pain 10:149-167, 1981 Carstens E, Klumpp D, Zimmermann M: Differential inhibitory effects of medial and lateral midbrain stimulation on spinal neuronal discharges to noxious skin heating in the cat. J Neurophysiol 43:332-342, 1980 Carstens E, Klumpp D, Zimmermann M: The opiate antagonist, naloxone, does not affect descending inhibition from midbrain of nociceptive spinal neuronal discharges in the cat. Neurosci Lett 11:323-327, 1979 Carstens E, Klumpp D, Zimmermann M: Time course and effective sites for inhibition from midbrain periaqueductal gray of spinal dorsal horn neuronal responses to cutaneous stimuli in the cat. Exp Brain Res 38:425-430, 1980 Carstens E, Yokota T, Zimmermann M: Inhibition of spinal neuronal responses to noxious skin heating by stimulation of mesencephalic periaqueductal gray in the cat. J Neurophysiol 42:558-568, 1979 Carstens E, Zimmermann M: The opiate antagonist naloxone does not consistently block inhibition of spinal nociceptive transmission produced by stimulation in lateral midbrain reticular formation of the cat. Neurosci Lett 20:335-339, 1980 Casey KL, Morrow TJ: Ventral posterior thalamic neurons differentially responsive to noxious stimulation of the awake monkey. Science 221:675-677, 1983 Cervero F, Iggo A, Molony V: An electrophysiological study of neurones in the substantia gelatinosa rolandi of the cat's spinal cord. J Exp Physiol 64:297-314, 1979 31. Cervero F, Iggo A, Molony V: Segmental and intersegmental organization of neurones in the substantia gelatinosa rolandi of the cat's spinal cord. J Exp Physiol 64:315-326, 1979 32. 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Chayen MS, Rudick V, Borvine A: Pain control with epidural injection of morphine. Anesthesiology 53:338-339, 1980 7. Cohen FL: Postsurgical pain relief: Patients' status and nurses' medication choices. Pain 9:265-274, 1980 8. Croze S, Duclaux R: Thermal pain in humans: Influence of the rate of stimulation. Brain Res 157:418-421, 1978 9. Devor M: Nerve pathophysiology and mechanisms of pain in causalgia. J Auton Nerv Syst 7:371-384, 1983 10. File SE: Naloxone reduces social and exploratory activity in the rat. Psychopharmacology (Berlin) 71:41-44, 1980 11. Gracely RH, Dubner R: Pain assessment in humans—a reply to Hall. Pain 11:109120, 1981 12. Holden C: Pain, dying, and the health care system. Science 203:984-986, 1979 13. Jacquet YF: Different behavioral effects following intracerebral, intracerebroventricular or intraperitoneal injections of naloxone in the rat. Behav Brain Res 1:543-546, 1980 14. Kenton B, Coger R, Crue B, et al: Peripheral fiber correlates to noxious thermal stimulation in humans. Neurosci Lett 17:301-306, 1980 15. MacDonald AJR: Abnormally tender muscle regions and associated painful movements. Pain 8:197-205, 1980 16. Maruyama Y, Shimoji K, Shimizu H, et al: Effects of morphine on human spinal cord and peripheral nervous activities. Pain 8:63-73, 1980 17. Nashold BS, Ostdahl RH: Dorsal root entry zone lesions for pain relief. J Neurosurg 51:59-69, 1979 18. Sherman RA, Sherman CJ, Gall NG: A survey of current phantom limb pain treatment in the United States. Pain 8:85-99, 1980 19. Strassburg HM, Thoden U, Mundinger F: Mesencephalic chronic electrodes in pain patients. Appl Neurophysiol 42:284-293, 1979 20. Varni JW, Gilbert A, Dietrich SL: Behavioral medicine in pain and analgesia in management for the hemophilic child with factor VIII inhibitor. Pain 11:121126, 1981 21. Wahlstrom A, Terenius L: Factor in human CSF with apparent morphine-antagonistic properties. Acta Physiol Scand 110:427-429, 1980 22. Walker JM, Moises HC, Coy DH, et al: Nonopiate effects of dynorphin and destyr-dynorphin. Science 218:1136-1138, 1982 23. Watson SJ, Khachaturian H, Akil H, et al: Comparison of the distribution of dynorphin systems and enkephalin sysPHYSICAL THERAPY
  • 16. PRACTICE terns in brain. Science 218:1134-1136, 1982 24. Wilier JC, Bussel B: Evidence for a direct spinal mechanism in morphine-induced inhibition of nociceptive reflexes in humans. Brain Res 187:212-215, 1980 PAIN: ACUPUNCTURE 1. Bragin EO, Vasilenko GF, Durinjan RA: The study of the central grey matter in mechanisms of different kinds of analgesia: Effects of lesions. Pain 16:33-40, 1983 2. Brattberg G: Acupuncture therapy for tennis elbow. Pain 16:285-288, 1983 3. Chapman CR, Colpitts YM, Benedetti C, et al: Evoked potential assessment of acupunctural analgesia: Attempted reversal with naloxone. Pain 9:183-197, 1980 4. Chapman CR, Sato T, Martin RW, et al: Comparative effects of acupuncture in Japan and the United States on dental pain perception. Pain 12:319-328, 1982 5. Cheng RSS, Pomeranz BH: Electroacupuncture analgesia could be mediated by at least two pain-relieving mechanisms: Endorphin and non-endorphin systems. Life Sci 25:1957-1962, 1979 6. Cheng RSS, Pomeranz BH: Electroacupuncture analgesia is mediated by stereospecific opiate receptors and is reversed by antagonists of type I receptors. Life Sci 26:631-638, 1980 7. Cheng RSS, Pomeranz BH: Monoaminergic mechanism of electroacupuncture analgesia. Brain Res 215:77-92, 1981 8. Cheng RSS, Pomeranz BH, Yu G: Electroacupuncture treatment of morphinedependent mice reduces signs of withdrawal, without showing cross-tolerance. Eur J Pharmacol 68:477-481, 1980 9. Crosby WH, Ulett GA: Acupuncture treatments for pain relief. JAMA 245:768-769, 1981 10. Dimitrijevic MR, Faganel J, Young RR: Underlying mechanisms of the effect of spinal cord stimulation in motor disorders. Appl Neurophysiol 44:133-140, 1981 11. Epler DC: Bloodletting in early Chinese medicine and its relation to the origin of acupuncture. Bull Hist Med 54:337-367, 1980 12. Eriksson MBE, Sjolund BH, Nielzen S: Long term results of peripheral conditioning stimulation as an analgesic measure in chronic pain. Pain 6:335-347, 1979 13. Facchinetti F, Nappi G, Savoldi F, et al: Primary headaches: Reduced circulating beta-lipotropin and beta-endorphin levels with impaired reactivity to acupuncture. Cephalalgia 1:195-201, 1981 14. Fu T-C, Halenda SP, Dewey WL: The effect of hypophysectomy on acupuncture analgesia in the mouse. Brain Res 202:33-39, 1980 15. Gwei-Djen L, Needham J: A scientific basis for acupuncture? The Sciences 19:1-10,1979 16. Ha H, Tan E-C, Fukunaga H, et al: Naloxone reversal of acupuncture analgesia in the monkey. Exp Neurol 73:298-303, 1981 Volume 65 / Number 3, March 1985 17. Ha H, Wu RS, Contreras RA, et al: Measurement of pain threshold stimulation of tooth pulp afferents in the monkey. Exp Neurol 61:260-269, 1978 18. Handelmann GF, Quirion R: Neonatal exposure to morphine increases micro-opiate binding in the adult forebrain. Eur J Pharmacol 94:357-358, 1983 19. Higby D: The nature of pain in patients with cancer—a summary. J Med 13:253-255, 1982 20. Ho WKK, Wen HL, Lam S, et al: The influence of electro-acupuncture on naloxone-induced morphine withdrawal in mice: Elevation of brain opiate-like activity. Eur J Pharmacol 49:197-199, 1978 21. Homma I, Motomiya Y: The inhibitory effect of acupuncture on the tonic vibration reflex (TVR) in man. Neurosci Lett 28:315-318, 1982 22. Homma S, Homma I: Inhibitory effect of acupuncture of the vibration-induced grasp reflex in man. Neurosci Lett 32:209-212, 1982 23. Iriki A: Site and action of electroacupuncture-induced effects on the rat jawopening reflex. Exp Neurol 75:36-50, 1982 24. Iriki A, Toda K: Morphine and electroacupuncture: Comparison of the effects on the cortical evoked responses after tooth pulp stimulation in rats. Eur J Pharmacol 68:83-87, 1980 25. Ishiko N, Yamamoto T, Murayama N, et al: Electroacupuncture: Current strength-duration relationship for initiation of hypesthesia in man. Neurosci Lett 8:273-276, 1978 26. Kawakita K: Role of the polymodal receptors in acupuncture analgesia of the rat. Comparative Medicine East and West 6:312-321, 1982 27. Kawakita K, Funakoshi M: Suppression of the jaw-opening reflex by conditioning A-delta fiber stimulation and electroacupuncture in the rat. Exp Neurol 78:461465, 1982 28. Kerr FWL, Wilson PR, Nijensohn DE: Acupuncture reduces the trigeminal evoked response in decerebrate cats. Exp Neurol 61:84-95, 1978 29. Kline RL, Yeung KY, Calaresu FR: Role of somatic nerves in the cardiovascular responses to stimulation of an acupuncture point in anesthetized rabbits. Exp Neurol 61:561-570, 1978 30. Lamontagne Y, Annable L, Gagnon MA: Acupuncture for smokers: Lack of long-term therapeutic effect in a controlled study. Can Med Assoc J 122:787-790, 1980 31. Lee MHM, Zaretsky HH, McMeniman M: Acupuncture analgesia-assessment using electric tooth-pulp stimulation: Preliminary report. NY State J Med 78:1687-1690, 1978 32. Lewit K: The needle effect in the relief of myofascial pain. Pain 6:83-90, 1979 33. Lewith GT, Field J, Machin D: Acupuncture compared with placebo in post-herpetic pain. Pain 17:361-368, 1983 34. Lewith GT, Machin D: On the evaluation of the clinical effects of acupuncture. Pain 16:111-127, 1983 35. Lu G-W: Characteristics of afferent fiber innervation on acupuncture points zusanli. Am J Physiol 345:606-612, 1983 36. Mao W, Ghia JN, Scott DS, et al: High versus low intensity acupuncture analgesia for treatment of chronic pain: Effects on platelet serotonin. Pain 8:331342, 1980 37. Melzack R, Katz J: Ariculotherapy fails to relieve chronic pain: A controlled crossover study. JAMA 251:1041 -1043, 1984 38. Monga TN, Jaksic T: Acupuncture in phantom limb pain. Arch Phys Med Rehabil 62:229-231,1981 39. Nappi G, Facchinette F, Bono G, et al: Plasma opioid levels in post-traumatic chronic headache and trigeminal neuralgia: Maintained response to acupuncture. Headache 22:276-279, 1982 40. Nappi G, Facchinetti F, Legnante G, et al: Different releasing effects of traditional manual acupuncture and electroacupuncture on proopiocortin-related peptides. Acupunct Electrother Res 7:93-103, 1982 41. Oleson TD, Kroening RJ, Bresler DE: An experimental evaluation of auricular diagnosis: The somatotopic mapping of musculoskeletal pain at ear acupuncture sets. Pain 8:217-229, 1980 42. Pomeranz B: Do endorphins mediate acupuncture analgesia? In Costa E, Trabucci M (eds): Advances in Biochemical Psychopharmacology, New York, NY, Raven Press, 1978, vol 18, pp 351-359 43. Pomeranz B, Paley D: Electroacupuncture hypalgesia is mediated by afferent nerve impulses: An electrophysiological study in mice. Exp Neurol 66:398-402, 1979 44. Pullan PT, Finch PM, Yuen RWM, et al: Endogenous opiates modulate release of growth hormone in response to electroacupuncture. Life Sci 32:1705-1709, 1983 45. Reshetnyak VK, Meizerov EE, Durinyan RA: Changes in functional activity of the large hemispheric cortex and central gray matter in response to electroacupuncture. Research findings from the Central Research Institute of Reflexotherapy, Moscow, 1982 46. Rico RC, Hobika GH, Avellanosa AM, et al: Use of intrathecal and epidural morphine for pain relief in patients with malignant diseases: A preliminary report. J Med 13:223-231, 1982 47. Rico RC, Trudnowski RJ: Studies with electro-acupuncture. J Med 13:247251,1982 48. Riscalla LM: Toward establishing scientific credibility in acupuncture research. Med Hypotheses 5:221-224, 1979 49. Sandrew BB, Yang RCC, Wang SC: Electro-acupuncture analgesia in monkeys: A behavioral and neurophysiological assessment. Arch Int Pharmacodyn Ther 231:274-284, 1978 50. Sarnat HB, Morrissy RT: Idiopathic torticollis: Sternocleidomastoid myopathy and accessory neuropathy. Muscle Nerve 4:374-380, 1981 329
  • 17. PRACTICE 51. Shiner G: Relief from chronic pain: Stimulating the "Morphine Within." Research Resources Reporter 5:1-5, 1981 52. Sodipo JOA: Therapeutic acupuncture for chronic pain. Pain 7:359-365, 1979 53. Toda K: Effects of electro-acupuncture on rat jaw opening reflex elicited by tooth pulp stimulation. Jpn J Physiol 28:485497, 1978 54. Toda K, Atsushi I, Tanaka H: Electroacupuncture suppresses the cortical evoked responses in somatosensory I and II areas after tooth pulp stimulation in rat. Jpn J Physiol 30:487-490, 1980 55. Toda K, Ichioka M: Afferent nerve information underlying the effects of electroacupuncture in rat. Exp Neurol 65:457-561, 1979 56. Toda K, Ichioka M, Iriki A, et al: Electroacupuncture effects on the field potentials in the caudal part of the spinal trigeminal nucleus evoked by tooth pulp stimulation in rat. Exp Neurol 64:704709, 1979 57. Toda K, Iriki A: Effects of electroacupuncture on thalamic evoked responses recorded from the ventrobasal complex and posterior nuclear group after tooth pulp stimulation in rat. Exp Neurol 66:419-422, 1979 58. Trudnowski RJ: Current concepts in providing pain relief for cancer patients: Introductory remarks. J Med 13:145, 1982 59. Zhang A, Pan X, Xu S, et al: Endorphins and acupuncture analgesia. Chin Med J [Engl] 93:673-680, 1980 PAIN: NEUROPHARMACOLOGICAL A. Endogenous Opiates (enkephalins)—Human 1. Akil H, Watson SJ, Sullivan S, et al: Enkephalin-like material in normal human CSF: Measurement and levels. Life Sci 23:121-126, 1978 2. Almay BGL, Johansson F, Von Knorring L, et al: Endorphins in chronic pain. I. Differences in CSF endorphin levels between organic and psychogenic pain syndromes. Pain 5:153-162, 1978 3. Amano K, Kitamura K, Kawamura H, et al: Alterations of immunoreactive betaendorphin in the third ventricular fluid in response to electrical stimulation of the human periaqueductal gray matter. Appl Neurophysiol 43:150-158, 1980 4. Bjorndal N, Casey DE, Gerfach J: Enkephalin, morphine and naloxone in tardive dyskinesia. Psychopharmacology 69:133-136, 1980 5. Budd K: Psychotropic drugs in the treatment of chronic pain. Anaesthesia 33:531-534, 1978 6. Carr DB, Bullen BA, Skrinar GS, et al: Physical conditioning facilitates the exercise-induced secretion of beta-endorphin and beta-lipotropin in women. N Engl J Med 305:560-563, 1981 7. Chery-Croze S, Duclaux R: Discrimination of painful stimuli in human beings: Influence of stimulation area. J Neurophysiol 44:1-10, 1980 330 8. Chou J, Tang J, Costa E: MET5-Enkephalin-ARG6-PHE7 content of human and rabbit plasma. Life Sci 32:2589-2595, 1983 9. Czlonkowski A, Costa T, Przewlocki R, et al: Opiate receptor binding sites in human spinal cord. Brain Res 267:392396, 1983 10. deLanerolle NC, Lamotte CC: The human spinal cord: Substance P and methionine-enkephalin immunoreactivity. J Neurosci 2:1369-1386, 1982 11. Fessler RG, Brown FD, Rachlin JR, et al: Elevated Beta-endorphin in cerebrospinal fluid after electrical brain stimulation: Artifact of contrast infusion? Science 224:1017-1018, 1984 12. Foley KM, Kourides IA, Inturrisi CE, et al: Beta-endorphin: Analgesic and hormonal effects in humans. Proc Natl Acad Sci USA 76:5377-5381, 1979 13. Furui T, Kageyama N, Kuwayama A, et al: Increase of beta-endorphin in cerebrospinal fluid after removal of ACTH-secreting pituitary adenomas. Pain 11:127-132, 1981 14. Furui T, Kageyama N, Haga T, et al: Radioreceptor assay of methionine-enkephalin-like substance in human cerebrospinalfluid.Pain 9:63-72, 1980 15. Gerner RH, Sharp B: CSF beta-endorphin-immunoreactivity in normal, schizophrenic, depressed, manic and anorexic subjects. Brain Res 237:244-247, 1982 16. Gintzler AR: Endorphin-mediated increases in pain threshold during pregnancy. Science 210:193-195, 1980 17. Gramsch C, Hollt V, Mehraein P, et al: Regional distribution of methionine-enkephalin- and beta-endorphin-like immunoreactivity in human brain and pituitary. Brain Res 171:261-270, 1979 18. Grevert P, Albert LH, Goldstein A: Partial antagonism of placebo analgesia by naloxone. Pain 16:129-143, 1983 19. Hollt V, Muller OA, Fahlbusch R: Betaendorphin in human plasma: Basal and pathologically elevated levels. Life Sci 25:27-44, 1979 20. Hosobuchi Y, Lamb S, Baskin D: Tryptophan loading may reverse tolerance to opiate analgesics in humans: A preliminary report. Pain 9:161-169, 1980 21. Houck JC, Kimball C, Chang C, et al: Placental beta-endorphin-like peptides. Science 207:78-80, 1980 22. Kaiya H, Tanaka T, Takeuchi K, et al: Decreased level of beta endorphin-like immunoreactivity in cerebrospinal fluid of patients with senile dementia of Alzheimer type. Life Sci 33:1039-1043, 1983 23. LaMotte CC, deLanerolle NC: Human spinal neurons: Innervation by both substance P and enkephalin. Neuroscience 6:713-723, 1981 24. Levine JD, Gordon NC, Smith R, et al: Analgesic responses to morphine and placebo in individuals with postoperative pain. Pain 10:379-389, 1981 25. Lewis JW, Tordoff MG, Sherman JE, et al: Adrenal medullary enkephalin-like peptides may mediate opioid stress analgesia. Science 217:557-559, 1982 26. McCain HW, Lamster IB, Bozzone JM, et al: B-Endorphin modulates human immune activity via non-opiate receptor mechanisms. Life Sci 31:1619-1624, 1982 27. Naber D, Pickar D, Dionne RA, et al: Assay of endogenous opiate receptor ligands in human CSF and plasma. Subst Alcohol Actions Misuse 1:83-91, 1980 28. Nicoll RA, Alger BE, Jahr CE: Peptides as putative excitatory neurotransmitters: Carnosine, enkephalin, substance P and TRH. Proc R Soc Lond [Biol] 210:13331340, 1980 29. Nyberg F, Wahlstrom A, Sjolund B, et al: Characterization of electrophoretically separable endorphins in human CSF. Brain Res 259:267-274, 1983 30. Piercey MF, Schroeder LA: Spinal and supraspinal sites for morphine and nefopam analgesia in the mouse. Eur J Pharmacol 74:135-140, 1981 31. Piercey MF, Varner K, Schroeder LA: Analgesic activity of intraspinally administered dynorphin and ethylketocyclazocine. Eur J Pharmacol 80:283-284, 1982 32. Pique L, Bertagna X, Javoy-Agid F, et al: Simultaneous measurement of betaendorphin and y-lipotropin-like peptides in the human hypothalamus. Neuropeptides 2:99-108, 1981 33. Quails PJ, Sheehan PW: Electromyograph biofeedback as a relaxation technique: A critical appraisal and reassessment. Psychol Bull 90:21-42, 1981 34. Richardson DE: Analgesia produced by stimulation of various sites in the human beta-endorphin system. Appl Neurophysiol 45:116-122, 1982 35. Rossier J, Bloom FE, Guillemin R: Stimulation of human periaqueductal gray for pain relief increases immunoreactive beta-endorphin in ventricular fluid. Science 203:279-281, 1979 36. Sana A, Wilson SP, Molnar A, et al: Substance P and opiate-like peptides in human adrenal medulla. Neurosci Lett 20:195-200, 1980 37. Sarne Y, Azov R, Weissman BA: A stable enkephalin-like immunoreactive substance in human CSF. Brain Res 151:399-403, 1978 38. Sarne Y, Gil-Ad I, Laron Z: Regulation of hypophysial secretion by endogenous opiates: Humoral endorphin stimulates the release of growth hormone. Life Sci 28:681-686, 1981 39. Same Y, Weissman BA, Keren O, et al: Humoral endorphin: A new endogenous factor with opiate-like activity. Life Sci 28:673-680, 1981 40. Scott DS: Treatment of the myofascial pain-dysfunction syndrome: Psychological aspects. J Am Dent Assoc 101:611 616, 1980 41. Stacher G, Bauer P, Steinringer H, et al: Effects of the synthetic enkephalin analogue FK 33-824 on pain threshold and pain tolerance in man. Pain 7:159-172, 1979 42. Steinbrook RA, Carr DB, Datta S, et al: Dissociation of plasma and cerebrospinal fluid beta-endorphin-like immunoactivity levels during pregnancy and parturition. Anesth Analg 61:893-897, 1982 PHYSICAL THERAPY
  • 18. PRACTICE 43. Suda T, Liotta AS, Krieger DT: BetaEndorphin is not detectable in plasma from normal human subjects. Science 202:221-223, 1978 44. Tamsen A, Sukurada T, Wahlstrom A, et al: Postoperative demand for analgesics in relation to individual levels of endorphin and substance P in cerebrospinal fluid. Pain 13:171-183, 1982 45. Taquet H, Javoy-Agid F, Hamon M, et al: Parkinson's disease affects differently met- and leu-enkephalin in the human brain. Brain Res 280:379-382, 1983 46. Volavka J, Bauman J, Pevnick J, et al: Short-term hormone effects of naloxone in man. Psychoneuroendocrinology 5: 225-234, 1980 47. Von Knorring L, Almay BGL, Johansson F, et al: Circannual variation in concentrations of endorphins in cerebrospinal fluid. Pain 12:265-272, 1982 48. Von Knorring L, Almay BGL, Johansson F, et al: Endorphins in CSF of chronic pain patients, in relation to augmentingreducing response in visual averaged evoked response. Neuropsychobiology 5:322-326, 1979 49. Von Knorring L, Almay BGL, Johansson F, et al: Pain perception and endorphin levels in cerebrospinal fluid. Pain 5:359365, 1978 50. Wilier JC, Albe-Fessard D: Electrophysiological evidence for a release of endogenous opiates in stress-induced analgesia in man. Brain Res 198:419-426, 1980 51. Yaksh TL, Elde RP: Release of methionine-enkephalin immunoreactivity from the rat spinal cord in vivo. Eur J Pharmacol 63:359-362, 1980 8. 9. 10. 11. 12. 13. 14. 15. PAIN: NEUROPHARMACOLOGICAL B. Endogenous Opiates (enkephalins)—Animal 1. Adler MW: The in vivo differentiation of opiate receptors: Introduction. Life Sci 28:1543-1545, 1981 2. Alleva E, Castellano C, Oliverio A: Effects of L- and D-amino acids on analgesia and locomotor activity of mice: Their interaction with morphine. Brain Res 198:249-252, 1980 3. Antelman SM, Rowland N: Endogenous opiates and stress-induced eating. Science 214:1149, 1981 4. Armitage SE, Baldwin BA, Vince MA: Opiate receptor function may be modulated through an oxidation-reduction mechanism. Science 208:1171-1174, 1980 5. Aronin N, DiFiglia M, Liotta AS, et al: Ultrastructural localization and biochemical features of immunoreactive leu-enkephalin in monkey dorsal horn. J Neurosci 1:561-577, 1981 6. Audigier Y, Mazarguil H, Gout R, et al: Structure-activity relationships of enkephalin analogs at opiate and enkephalin receptors: Correlation with analgesia. Eur J Pharmacol 63:35-46, 1980 7. Azami J, Llewelyn MB, Roberts MHT: Antagonism of the analgesic effects of Volume 65 / Number 3, March 1985 16. 17. 18. 19. 20. 21. 22. systemically administered morphine by injection of naloxone intracerebrally and lesions of nucleus raphe magnus. J Physiol (Lond) 306:16-17, 1979 Azami J, Llewelyn MB, Roberts MHT: The analgesic effects of morphine microinjected into nucleus reticularis paragigantocellularis—comparison with nucleus raphe magnus and the effects of nucleus raphe magnus lesions. J Physiol (Lond) 306:17-18, 1979 Barker JL, Neale JH, Smith TG Jr, et al: Opiate peptide modulation of amino acid responses suggests novel form of neuronal communication. Science 199:1451-1453, 1978 Barker JL, Smith TG Jr, Neale JH: Multiple membrane actions of enkephalin revealed using cultured spinal neurons. Brain Res 154:153-158, 1978 Barrett RW, Vaught JL: The effects of receptor selective opioid peptides on morphine-induced analgesia. Eur J Pharmacol 80:427-430, 1982 Beitz AJ: The sites of origin of brain stem neurotensin and serotonin projections to the rodent nucleus raphe magnus. J Neurosci 2:829-842, 1982 Billet M, Elghozi JL, Meyer P, et al: Central cardiovascular effects on narcotic analgesics and enkephalins in rats. Br J Pharmacol 71:365-369, 1980 Bloom F, Battenberg E, Rossier J, et al: Neurons containing beta-endorphin in rat brain exist separately from those containing enkephalin: Immunocytochemical studies. Proc Natl Acad Sci USA 75:1591-1595, 1978 Blum K, Briggs AH, Elston SFA, et al: Reduced leucine-enkephalin-like immunoreactive substance in hamster basal ganglia after long-term ethanol exposure. Science 216:1425-1426, 1982 Botticelli LJ, Wurtman RJ: Septohippocampal cholinergic neurons are regulated trans-synaptically by endorphin and corticotropin neuropeptides. J Neurosci 2:1316-1321, 1982 Carr DB, Bergland R, Hamilton A, et al: Endotoxin-stimulated opioid peptide secretion: Two secretory pools and feedback control in vivo. Science 217:845-848, 1982 Cesselin F, Oliveras JL, Bourgoin S, et al: Increased levels of met-enkephalinlike material in the CSF of anaesthetized cats after tooth pulp stimulation. Brain Res 237:325-338, 1982 Clark WG, Bemardini GL: Beta-endorphin-induced hyperthermia in the cat. Peptides (Fayetteville) 2:371-373, 1981 Clark WG: Effects of opioid peptides on thermoregulation. Fed Proc 40: 2754-2759, 1981 Cone RI, Weber E, Barchas JD, et al: Regional distribution of dynorphin and neo-endorphin peptides in rat brain, spinal cord, and pituitary. J Neurosci 3:2146-2152, 1983 Craves FB, Zalc B, Leybin L, et al: Antibodies to cerebroside sulfate inhibit the effects of morphine and beta-endorphin. Science 207:75-76, 1980 23. Cuello AC: Central distribution of opioid peptides. Br Med Bull 39:11-16, 1983 24. Davies J, Dray A: Pharmacological and electrophysiological studies of morphine and enkephalin on rat supraspinal neurones and cat spinal neurones. Br J Pharmac 63:87-96, 1978 25. Egan TM, North RA: Both mu and delta opiate receptors exist on the same neuron. Science 214:923-924, 1981 26. Ferrara P, Li CH: Beta-Endorphin: Characteristics of binding sites in rabbit spinal cord. Proc Natl Acad Sci USA 77:5746-5748, 1980 27. Foutz AS, Dauthier C, Kerdelhue B: Beta-endorphin plasma levels during neuromuscular blockade in unanesthetized cat. Brain Research 263:119123, 1983 28. Frenk H, Urca G, Liebeskind JC: Epileptic properties of leucine- and methionine-enkephalin: Comparison with morphine and reversibility by naloxone. Brain Res 147:327-337, 1978 29. Frigeni V, Bruno F, Carenzi A, et al: Analgesia and motor activity elicited by morphine and enkephalins in two inbred strains of mice. J Pharm Pharmacol 30:310, 1978 30. Fu T-C, Dewey WL: A new technique for the in vivo bioassay of opiates and other drugs on mouse spinal cord. Eur J Pharmacol 74:239-242, 1981 31. Gambert SR, Garthwaite TL, Pontzer CH, et al: Fasting associated with decrease in hypothalamic beta-endorphin. Science 210:1271-1272, 1980 32. Gold MS, Byck R, Sweeney DR, et al: Endorphin-locus coeruleus connection mediates opiate action and withdrawal. Biomedicine 30:1-4, 1979 33. Graf L, Miglecz E, Bajusz S, et al: Metenkephalin attentuates morphine tolerance in rats. Eur J Pharmacol 58:345- 346, 1979 34. Grau JW, Hyson RL, Maier SF, et al: Long-term stress-induced analgesia and activation of the opiate system. Science 213:1409-1411, 1981 35. Havlicek V, Labella FS, Pinsky C, et al: Beta-Endorphin induces general anaesthesia by an interaction with opiate receptors. Can Anaesth Soc J 27:535- 539, 1980 36. Haynes LW, Zakarian S: Morphological differentiation of enkephalin-containing neurones in tissue culture. J Physiol (Lond) 295:34-35, 1979 37. Haynes LW: Development of neurotensin-immunoreactive nerve cells in organotypic cultures of embryonic rat spinal cord. Neurosci Lett 19:185-190, 1980 38. Haynes LW, Smyth DG, Zakarian S: Beta endorphin immunoreactivity in developing rat spinal cord cultures. J Physiol (Lond) 301:91-92, 1979 39. Haynes LW, Zakarian S: Microanatomy of enkephalin-containing neurones in the developing rat spinal cord in vitro. Neuroscience 6:1899-1916,1981 40. Hazum E, Chang K-J, Cuatrecasas P: Opiate (enkephalin) receptors of neuroblastoma cells: Occurrence in clusters on the cell surface. Science 206:10771079, 1979 331
  • 19. 41. Hazum E, Chang K-J, Cuatrecasas P: Specific nonopiate receptors for betaendorphin. Science 205:1033-1035, 1979 42. Hentall ID, Fields HL: Actions of opiates, substance P, and serotonin on the excitability of primary afferent terminals and observations on interneuronal activity in the neonatal rat's dorsal horn in vitro. Neuroscience 9:521-528, 1983 43. Hill RG, Pepper CM: The depression of thalamic nociceptive neurones by Dala2, and D-leu5-enkephalin. Eur J Pharmacol 47:223-225, 1978 44. Hughes J: Biogenesis, release and inactivation of enkephalins and dynaorphins. Br Med Bull 39:17-24, 1983 45. Huidobro-Toro JP, Yoshimura K, Way EL: Application of an irreversible opiate antagonist (beta-FNA, beta-Funal-trexamine) to demonstrate dynorphin selectivity for K-opioid sites. Life Sci 31:2409-2416,1982 46. Hunt SP, Kelly JS, Emson PC: The electron microscopic localization of methionine-enkephalin within the superficial layers (I and II) of the spinal cord. 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