Recommended dose = 1 mg/kg of lidocaine and bupivicaine in the same syringe.
Up to 8 mg/kg IV of Lidocaine Cats 0.5 mg/kg q 5-20 min x 3
Decreased cardiac output and vasodilation result in arterial hypotension Cardiovascular toxicity Permanent nerve damage Horner’s syndrome Unilateral deafness Ataxia Seizures
Which of the following is not a complication of regional nerve blocks? Cardiovascular toxicity Permanent nerve damage Horner’s syndrome Unilateral deafness Ataxia Bupivicaine systemically adminstered produces seizures in dogs at 5 mg/kg. Ventricualar Fib Decreased cardiac output and vasodilation result in arterial hypotension Complications resulting from oral nerve blocks have been described in human dentistry and oral surgery literature. Although extremely rare, permanent damage of the inferior alveolar nerve, lingual nerve or both has occurred as a result of inferior alveolar nerve blocks. Incidence has been reported to be anywhere between 1:26,762 and 1:160,571.8 Toxic doses of bupivicaine have been reported to cause cardiovascular toxicity and death, although this is extremely rare.9 Local anesthesia is not used in humans with malignant hyperthermia because of the potential for complications.10 Neurological complications include facial nerve palsey, transient amaurosis, Horner’s syndrome, transient nerve paralysis and unilateral deafness.
Go to the web page. Click support material on the menu. There is a list of documents there that include the charts that I just showed you. Last time that I looked they could not yet be downloaded directly from the server, however if you email them with your specific request they will send them to you as an email attachement.
ROSTRAL MAXILLARY (INFRAORBITAL) REGIONAL BLOCK The rostral maxillary block provides infiltration of the lidocaine/bupivicaine combination adjacent to the infraorbital nerve and the rostral maxillary alveolar nerve within the infraorbital canal. (Figures 2 and 3) The latter leaves the inferior alveolar nerve within the canal to enter the incisivomaxillary foramen to innervate the canine and incisor teeth. In addition the first three premolar teeth as well as the maxillary bone and surrounding soft tissue are affected. To perform this block, retract the lip dorsally. Palpate the infraorbital neurovascular bundle beneath the vestibular mucosa. This is a large cylindrical band that exits the infraorbital canal dorsal to the distal root of the maxillary third premolar. The thumb of one hand can be used to retract the bundle dorsally. With the opposite hand the needle is advanced close to the maxillary bone ventral to the retracted bundle in a rostral to caudal direction to a point just inside the canal. The needle should pass without engaging bone. If bone is encountered the needle is withdrawn slightly and redirected until it passes resistance free into the canal. Proper insertion can be confirmed by gentle lateral movement of the syringe whereby the needle will meet resistance with the lateral canal wall. The infraorbital nerve block affects bone, tooth and soft tissue from the maxillary 3rd premolar extending rostrally to the midline. Palpate the infraorbital neurovascular bundle. Direct the needle as shown against the maxillary bone palatal to the bundle to enter the foramen. Some advocate placing a finger over the foramen for 30-60 seconds to facilitate caudal passage of the agent. I prefer to place the needle comfortably in the canal as an alternative. As with all local or regional blocks the plunger should be withdrawn to check for flash prior to injection. If blood is present the needle should be withdrawn and redirected.
CAUDAL MAXILLARY (MAXILLARY) REGIONAL BLOCK The caudal maxillary block allows infiltration of the local anesthetic combination adjacent to the infraorbital nerve and the pterygopalatine nerve caudal to the second maxillary molar. (Figures 4 and 5) These nerves are branches of the maxillary nerve that supply sensory innervation to the maxilla. In addition to the structures affected by the infraorbital block it will anesthetize the caudal cheek teeth and associated bone and soft tissue. The soft palatal mucosa and hard palatal mucosa and bone will also be affected by this block. To perform this block the mouth is opened wide and the lips retracted caudally at the lateral commissure. The needle is directed in a dorsal direction immediately behind the central portion of the maxillary second molar tooth. Advancement of the needle need not be more than a 2-4 millimeters depending upon patient size. The maxillary nerve block affects maxillary bone, tooth, soft tissue and the palatal bone and mucosa from the last molar rostrally to the midline. The needle is placed as shown behind the last molar and advanced a few mm past the point of entry. As an alternative 1 ½ inch needle may be used and the maxillary block performed through the infraorbital foramen by extending the needle distal to the pterygopalatine fossa.
ROSTRAL MANDIBULAR (MENTAL) REGIONAL BLOCK The rostral mandibular block infiltrates the rostral extent of the inferior alveolar nerve just before it exits the middle mental foramen. (Figures 6 and 7) The structures anesthetized include the incisors, the canine and the first three premolars. The adjacent bone and soft tissue are also affected. The middle mental foramen is located about 1/3 of the distance from the ventral border to the dorsal border of the mandible at the level of the mesial root of the second premolar. The landmark for infiltration is the mandibular labial frenulum. The frenulum is retracted ventrally. The needle is inserted at the rostral aspect of the frenulum and advanced along the mandibular bone to just enter the canal. If bone is encountered the needle should be backed out and redirected until the needle passes freely into the foramen. Placement can be confirmed by moving the syringe laterally to encounter the lateral aspect of the canal. The patient’s jaw, rather than the alveolar mucosa, will move slightly if the needle is within the canal. The mental nerve block gets the mandibular bone, teeth and soft tissue from the second premolar to the midline. The mandibular labial frenulum is retracted ventrally. The needle is directed into the mesial aspect of the frenulum and advanced against the bone distally to enter the middle mental foramen at the level of the distal frenulum.
CAUDAL MANDIBULAR (INFERIOR ALVEOLAR) REGIONAL BLOCK The caudal mandibular block is performed by infiltrating the inferior alveolar nerve prior to its entry into the mandibular foramen on the lingual aspect of the caudal mandibular body. (Figures 8 and 9) The lateral canthus of the eye is the landmark for this block. An imaginary plumb line is drawn from the lateral canthus of the eye directly to the ventral mandible. The needle is inserted into the skin at the lingual aspect of the ventral mandible at this point. The needle is advanced along the bone following the imaginary plumb line to a point 1/3 of the distance from the ventral to the dorsal mandible. The needle will now be in the vicinity of the mandibular foramen where the inferior alveolar nerve enters the mandibular canal. It is not critical to be exactly at the foramen. Radiographic dye studies indicate that the agent diffuses to encompass a large area around the point of infusion. (Figure 10) This technique blocks all of the teeth of the mandible on the side of infiltration as well as the adjacent bone and soft tissue. Although very uncommon, patients receiving an caudal mandibular nerve block have been known to traumatize their tongues by mastication in the postoperative period. Observation and proper recovery assistance during this period will eliminate this complication. Staff members monitoring the recovering patient should ensure visual confirmation that the tongue is not trapped between the carnassial teeth if the patient is recovered in lateral recumbency. Maintaining the patient in sternal recumbency precludes the tongue deviation expected when a patient is laterally recumbent.
The inferior alveolar nerve block affects bone, tooth and soft tissue of the entire mandible from the point of infiltration to the midline. A bony protruberance rostral to the angular process at the lingual aspect of the caudal ventral mandible can be palpated in many patients and may serve as the landmark for placement of the needle as shown. The lateral canthus is used as a landmark if this protruberance cannot be palpated. Your needle will now be in the vicinity of the mandibular foramen where the inferior alveolar nerve enters the mandibular canal. In the dog it is usually possible to palpate the notch of the caudal ventral mandible, cranial to the angular process.4 In the cat and some dogs the notch cannot be palpated. If the notch cannot be palpated, the point on the ventral mandible is located on a vertical plane with the midpoint of the zygomatic arch. This midpoint should be approximately located on a vertical with the lateral canthus. Insert the needle at the lingual aspect of the ventral mandible at this point. Advance the needle dorsally along the lingual aspect of the mandible to 1/3 the distance between the ventral and dorsal borders of the mandible.
I hear practitioners say, I don’t use local anesthetics because I don’t think that they do much. Why? Likely because they haven’t administered the drug at the correct site, in adequate concentration. Maybe they didn’t enhance the drug to make it more effective. So lets assume that some of these things I don’t think that they work that well. You have just learned in the discussion how local anesthetics are the only agent that acts on all 4 pathways of nociception. Human dentistry rely’s almost exclusively on local anesthesia for analgesia for their patients intraoperatively. So if the correct amount of agent is injected at the correct site then these agents are extremely effective. Lets assume that you have attended Dr. Genglers lab here and taken the information I have provided and go back to the practice to start using these blocks. Once we have finished this lecture you will have the correct dosing information. What can you do to increase the likelihood that you will be successful in getting the agent where it needs to go? Increase the volume or the amount that you give. If you are at the max dose in a small dog you can double the volume with saline. What else can you do? If you are well withing the max dose for the patient, administer another volume prior to completion of the procedure. “I have heard that patients chew their tongues after mandibular block” Nerve itself is not blocked (show slide of anatomy) Postitional. Monitor animals as you normally would during recovery. “All that trouble just for a couple of hours of effect?” Again, remember what we are doing based on physiology. We are effectively blocking all 4 pathways of nociception. Secondly we can greatly enhance the duration of effect by doing a few things. A. Adding epinephrine B. Adding an opiate C. Giving another injection at completion of the procedure Reg Anesth Pain Med. 2002 May-Jun;27(3):336. Buprenorphine added to the local anesthetic for brachial plexus block to provide postoperative analgesia in outpatients. The mean duration of postoperative pain relief following the injection of the local anesthetic alone was 5.3 (+/- 0.15) hours as compared with 17.4 (+/- 1.26) hours when buprenorphine was added, a difference that was statistically (and clinically) significant (P &lt;.0001). 40 ml of bup and 0.3 mg buprenex. . Related Articles, Links The addition of opioids to local anaesthetics in brachial plexus block: the comparative effects of morphine, buprenorphine and sufentanil.Bazin JE, Massoni C, Bruelle P, Fenies V, Groslier D, Schoeffler P: The addition of opioids to local anaesthetics in brachial plexus block: the comparative effects of morphine, buprenorphine and sufentanil. Anaesthesia. 1997 Sep;52(9):858-62 Departement d&apos;Anaesthesie et de Reanimation, Hopital Universitaire G. Montpied, Clermont-Ferrand, France. The median duration (range) of satisfactory analgesia was: 11.5 (8-15) h without an opioid, 21 (9-27) h with morphine, 20 (14-34) h with buprenorphine and 24.5 (11-38) h with sufentanil.
Robert Stein on 11/18/2007 2:56:43 pm ET &gt;&gt;&gt; This is the first I&apos;ve heard of this. I know about using morphine or even buprenorphine for epidurals, but not dental nerve blocks. Could you post more info, Bob? (Drugs, dosages, etc.) &lt;&lt;&lt; Brett Beckman brought this up a few years back. Several human studies showing that small doses of morphine or buprenorphine significantly extend patient benefit. Generally you see 0.003 mg/kg buprenorphine or 0.075 mg/kg morphine as the opioid/dose. Message Boards Link I have some of the references listed at the bottom of this vasg local anesthetic page:http://www.vasg.org/local_anesthetic_use.htm Pubmed: http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=11915063 http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&dopt=AbstractPlus&list_uids=15534532 http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=9349066 http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17823672&itool=pubmed_DocSum Robert M. Stein, DVM, DAAPMPresident, IVAPM Not an IVAPM Member?Please join:http://www.cvmbs.colostate.edu/ivapm/aboutus/2007membershipform.pdf &quot;Do No Harm - But First, Do Not Hurt.&quot; Claire Cooney on 11/22/2007 10:21:36 pm ET Thank you for the information. I was wondering if you can mix the buprenorphine or morphine with the bupivicaine in the same syringe for dental blocks???? Erica Feiste on 11/23/2007 7:46:40 am ET Yes. I mix lidocaine, bupivicaine, and morphine all in the same syringe. I figure the patient&apos;s total dose and then use small amounts of the mixture for each block. Robert Stein on 11/23/2007 11:09:20 am ET &gt;&gt;&gt; I mix lidocaine, bupivicaine, and morphine all in the same syringe. I figure the patient&apos;s total dose and then use small amounts of the mixture for each block. &lt;&lt;&lt; Me too - diluting drug 1:1 with sterile water if I need more volume. Robert M. Stein, DVM, DAAPMPresident, IVAPM Not an IVAPM Member?Please join:http://www.cvmbs.colostate.edu/ivapm/aboutus/2007membershipform.pdf &quot;Do No Harm - But First, Do Not Hurt.&quot; Shana Tanenbaum on 12/04/2007 4:21:39 pm ET &gt;&gt;&gt; http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=11915063 &lt;&lt;&lt; Reg Anesth Pain Med. 2002 Mar-Apr;27(2):162-7. Buprenorphine added to the local anesthetic for axillary brachial plexus block prolongs postoperative analgesia. Candido KD, Winnie AP, Ghaleb AH, Fattouh MW, Franco CD. Department of Anesthesiology and Pain Management, Cook County Hospital, Chicago, IL 60611, USA. [email_address] BACKGROUND AND OBJECTIVES: Buprenorphine added to local anesthetic solutions for supraclavicular block was found to triple postoperative analgesia duration in a previous study when compared with local anesthetic block alone. That study, however, did not control for potentially confounding factors, such as the possibility that buprenorphine was affecting analgesia through intramuscular absorption or via a spinal mechanism. To specifically delineate the role of buprenorphine in peripherally mediated opioid analgesia, the present study controlled for these 2 factors. METHODS: Sixty American Society of Anesthesiologists (ASA) P.S. I and II, consenting adults for upper extremity surgery, were prospectively assigned randomly in double-blind fashion to 1 of 3 groups. Group I received local anesthetic (1% mepivacaine, 0.2% tetracaine, epinephrine 1:200,000), 40 mL, plus buprenorphine, 0.3 mg, for axillary block, and intramuscular (IM) saline. Group II received local anesthetic-only axillary block, and IM buprenorphine 0.3 mg. Group III received local anesthetic-only axillary block and IM saline. Postoperative pain onset and intensity were compared, as was analgesic medication use. RESULTS: The mean duration of postoperative analgesia was 22.3 hours in Group I; 12.5 hours in group II, and 6.6 hours in group III. Differences between groups I and II were statistically significant (P =.0012). Differences both between groups I and III and II and III were also statistically significant (P &lt;.001). CONCLUSIONS: Buprenorphine-local anesthetic axillary perivascular brachial plexus block provided postoperative analgesia lasting 3 times longer than local anesthetic block alone and twice as long as buprenorphine given by IM injection plus local anesthetic-only block. This supports the concept of peripherally mediated opioid analgesia by buprenorphine. &gt;&gt;&gt;http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&dopt=AbstractPlus&list_uids=15534532&lt;&lt;&lt; Clin Orthop Relat Res. 2004 Nov;(428):125-30. Soft tissue and intra-articular injection of bupivacaine, epinephrine, and morphine has a beneficial effect after total knee arthroplasty. Lombardi AV Jr, Berend KR, Mallory TH, Dodds KL, Adams JB. Joint Implant Surgeons, Inc, Columbus, OH 43215, USA. [email_address] The purpose of this study was to determine if an intraoperative intraarticular and soft-tissue injection of local anaesthetic, epinephrine, and morphine has a beneficial effect for total knee arthroplasty. A control group of 138 patients (181 knees) received no intraoperative injection. The study group of 171 patients (197 knees) received intraoperative injection of 0.25% bupivacaine with epinephrine and morphine with 2/3 injected into the soft tissues and 1/3 injected into the joint. Patients having bilateral simultaneous procedures received a divided dose. The pain treatment protocol otherwise was identical. Pain, sedation, rescue narcotic usage, narcotic reversal and blood loss were examined. Pain levels during the immediate postoperative period, blood loss, and bleeding indices were reduced with injection. Considerably more control patients required rescue doses of narcotics. Preemptive analgesia with soft tissue and intra-articular injection of long-acting local anesthetic with epinephrine and morphine provides better pain control in the immediate postoperative period, decreases blood loss, and decreases the need for rescue narcotics and reversal agents. This simple, inexpensive method provides an effective adjunct to a multimodal approach in improving the postoperative course of primary total knee arthroplasty. &gt;&gt;&gt;http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=9349066&lt;&lt;&lt; Anaesthesia. 1997 Sep;52(9):858-62. The addition of opioids to local anaesthetics in brachial plexus block: the comparative effects of morphine, buprenorphine and sufentanil. Bazin JE, Massoni C, Bruelle P, Fenies V, Groslier D, Schoeffler P.Département d&apos;Anaesthésie et de Réanimation, Hôpital Universitaire G. Montpied, Clermont-Ferrand, France. We compared the duration of analgesia produced by a mixture of lignocaine and bupivacaine, either alone or combined with morphine (75 micrograms.kg-1), buprenorphine (3 micrograms.kg-1) or sufentanil (0.2 microgram.kg-1) in 80 patients after brachial plexus block for orthopaedic surgery of the upper limb. The characteristics of analgesia were evaluated hourly using a visual analogue scale. The analgesia was considered satisfactory for scores of 30 or less. The median duration (range) of satisfactory analgesia was: 11.5 (8-15) h without an opioid, 21 (9-27) h with morphine, 20 (14-34) h with buprenorphine and 24.5 (11-38) h with sufentanil. We conclude that the addition of an opioid to a local anaesthetic mixture lengthens the duration of analgesia. &gt;&gt;&gt;http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17823672&itool=pubmed_DocSum &lt;&lt;&lt; Quintessence Int. 2007 Sep;38(8):e484-9. Effect of intra-articular administration of buprenorphine after arthrocentesis of the temporomandibular joint: a pilot study. Präger TM, Mischkowski RA, Zöller JE. Charité-Universitätsmedizin Berlin, School of Dentistry, Institute of Orthodontics, Dentofacial Orthopedics and Pedodontics, Berlin, Germany. [email_address] OBJECTIVE: The purpose of this double-blind study was to evaluate the effect of intra-articular opioid injections on postoperative pain and joint mobility after arthrocentesis of the temporomandibular joint (TMJ). METHOD AND MATERIALS: Forty patients suffering from persistent pain in combination with anterior disc displacement (22 with reduction, 18 without reduction) and unresponsive to nonsurgical therapy underwent arthrocentesis of the affected TMJ under local anesthesia. All patients were randomly assigned to 2 groups. In group 1 (20 patients), 1 mL of buprenorphine solution was injected into the joint space at the end of the intervention; in group 2 (20 patients), 1 mL of saline was used. For postoperative pain management, all patients received Paracetamol ad libitum. Preoperatively and at postoperative days 2, 4, 7, and 14, individual pain levels were determined on a visual analogue scale together with maximum mouth opening. RESULTS: At days 2 and 4 after the intervention, remarkable differences were detectable between the 2 groups, showing a rapid normalization of joint mobility and pain scores in group 1; in contrast, improvement in group 2 was delayed. CONCLUSION: Intra-articular injections of long lasting opioids seem to influence joint mobility and pain positively within the first week after arthrocentesis.
Local injection of opiods at sites of inflammation produce profound analgesia. This action is not present in normal tissue. Contrast to local anesthetics that do not work in inflammed tissue. Inflammation stimulates the synthesis of receptors in the dorsal root ganglia axonal transport of opiod receptors to the periphery and increases their number (upregulates) on periopheral nerve terminals. Application to a nerve is less effective. Median duration of satisfactory analgesia: (N=80) 11.5 (8-15) h without an opioid 21.0 (9-27) h with morphine 20.0 (14-34) h with buprenorphine Bazin JE, Massoni C, Bruelle P, Fenies V, Groslier D, Schoeffler P: The addition of opioids to local anaesthetics in brachial plexus block: the comparative effects of morphine, buprenorphine and sufentanil. Anaesthesia. 1997 Sep;52(9):858-62 1: Neuroscience. 2004;129(2):473-9. Links Rapid upregulation of mu opioid receptor mRNA in dorsal root ganglia in response to peripheral inflammation depends on neuronal conduction. Puehler W, Zöllner C, Brack A, Shaqura MA, Krause H, Schäfer M, Stein C. Klinik für Anaesthesiologie und operative Intensivmedizin, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, D-12200 Berlin, Germany. firstname.lastname@example.org S.c. painful inflammation leads to an increase in axonal transport of opioid receptors from dorsal root ganglia (DRG) toward the periphery, thus causing a higher receptor density and enhanced opioid analgesia at the injured site. To examine whether this increase is related to transcription, the mRNA of Delta- (DOR) and mu-opioid receptor (MOR) in lumbar DRG was quantified by real time Light Cycler polymerase chain reaction (LC-PCR), and correlated to ligand binding in DRG and sciatic nerve. In normal DRG, DOR mRNA was seven times less abundantly expressed than MOR mRNA. After induction of unilateral paw inflammation, mRNA content for DOR remained unchanged, but a bi-phasic upregulation for MOR mRNA with an early peak at 1-2 h and a late increase at 96 h was found in ipsilateral DRG. As no changes were observed in DRG of the non-inflamed side, this effect was apparently not systemically mediated. A significant increase in binding of the MOR ligand DAMGO was detected after 24 h in DRG, and after early and late ligation in the sciatic nerve, indicating an enhanced axonal transport of MOR in response to inflammation. The early increase in MOR mRNA could be completely prevented by local anesthetic blockade of neuronal conduction in sciatic nerve. These data suggest that mRNA of the two opioid receptors DOR and MOR is differentially regulated in DRG during peripheral painful inflammation. The apparently increased axonal transport of MOR in response to this inflammation is preceded by upregulated mRNA-transcription, which is dependent on neuronal electrical activity. 1: Anesthesiology. 1998 Jul;89(1):190-201. Links Peripheral morphine administration blocks the development of hyperalgesia and allodynia after bone damage in the rat. Houghton AK, Valdez JG, Westlund KN. Department of Anatomy and Neurosciences, University of Texas Medical Branch, Galveston 77555-1069, USA. BACKGROUND: The current study aimed to assess whether local administration of morphine could block the development of hyperalgesia and allodynia in a rat model of osteotomy or bone damage. METHODS: Withdrawal responses to mechanical and thermal stimuli applied to the plantar surface of the hind paw were measured before and after bone damage. The bone was injured by drilling a 1-mm hole through the tibia during short-lasting general anesthesia. In separate groups of rats, the effects of administering morphine (20-80 microg), either into the marrow cavity or systemically, on the development of hyperalgesia and allodynia after bone damage were assessed. In an additional group of rats, a selective mu-opioid receptor antagonist, clocinnamox (0.15 mg), was administered into the marrow cavity before the administration of morphine (40 microg). RESULTS: In animals that received no drug treatment, hyperalgesia and allodynia peaked 2 h after injury. Injection of morphine (40 and 80 microg) into the marrow cavity immediately after bone injury prevented the development of hyperalgesia and allodynia. Clocinnamox (0.15 mg) injected into the marrow cavity before administration of morphine blocked the antihyperalgesic effect of morphine. CONCLUSION: This study shows that local application of a low dose of morphine effectively blocks the development of hyperalgesia and allodynia in a rat model of bone damage through mu-opioid receptor action. These findings provide further evidence that local application of morphine at the time of orthopedic surgery, bone graft, or bone marrow harvesting may reduce the amount of postoperative pain. 1: Eur J Pharmacol. 2007 Jul 30;568(1-3):124-33. Epub 2007 May 8. Links Reorganization of dorsal root ganglion neurons following chronic sciatic nerve constriction injury: correlation with morphine and lidocaine analgesia. Kolesnikov Y, El-Maarouf Abderrahman A, Rutinhauser U, Pasternak G. Department of Anesthesiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. email@example.com Chronic constriction injury of the sciatic nerve is an animal model for neuropathic pain. In this model, the analgesic potency of systemic morphine was significantly diminished in nerve-injured mice (ED(50) 19.4 mg/kg) compared with sham-operated mice (ED(50) 3.3 mg/kg) using a unilateral hot plate withdrawal test, with a similar reduction in sensitivity of intrathecal morphine. The sciatic nerve injury resulted in a reorganization of the dorsal root ganglion (DRG) neurons. Immunohistochemically, the chronic constriction injury triggered a withdrawal of C-fibers from the ipsilateral dorsal horn of the spinal cord. Although A-beta terminals centrally sprouted into Lamina II of the dorsal horn of the spinal cord, the peripheral A-beta fibers in the skin retracted from the epidermis to deeper layers of the dermis. To explore the functional significance of these dermal changes, we examined the topical morphine and lidocaine analgesia following chronic sciatic nerve constriction. Both morphine and lidocaine retained topical activity following chronic sciatic nerve injury, but their analgesic dose-response curves were shifted to the right when compared to sham-operated mice. Thus, the chronic nerve constriction injury model is associated with pathological changes in distribution of the central and peripheral axons of the dorsal root ganglion neurons that correspond to a decreased pharmacological sensitivity to topical analgesic agents. 1: Naunyn Schmiedebergs Arch Pharmacol. 2005 Nov;372(3):213-9. Epub 2005 Nov 8. Links Effects of the local administration of selective mu-, delta-and kappa-opioid receptor agonists on osteosarcoma-induced hyperalgesia. Baamonde A, Lastra A, Juárez L, García V, Hidalgo A, Menéndez L. Laboratorio de Farmacología, Facultad de Medicina, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, C/ Julián Clavería 6, 33006, Oviedo, Asturias, Spain. The stimulation of peripheral opioid receptors yields analgesic responses in a model of bone cancer-induced pain in mice. In order to know the type(s) of peripheral opiate receptors involved, the paw thermal withdrawal latencies were measured in C3H/HeJ mice bearing a tibial osteosarcoma, after administering selective agonists of mu-,delta-and kappa-opiate receptors. The peritumoral administration of DAGO (0.6-6 microg) inhibited the osteosarcoma-induced hyperalgesia at doses ineffective in healthy animals, the highest one even increasing the withdrawal latencies over the control values. Naloxone-methiodide (2 mg/kg) and cyprodime (1 mg/kg), but not naltrindole (0.1 mg/kg) nor nor-binaltorphimine (10 mg/kg), antagonized DAGO-induced analgesic effects, these therefore probably being mediated through peripheral mu-opioid receptors. The peritumoral injection of DPDPE (100 microg) induced analgesia which was inhibited by naloxone-methiodide and naltrindole but not by nor-binaltorphimine. Cyprodime partially antagonized the analgesia induced by 100 microg of DPDPE, but did not modify the effect induced by 30 microg of this agonist-a dose that restores the hyperalgesic latencies up to the control values. The antihyperalgesic effect induced by the peritumoral administration of U-50,488H (1 microg) was antagonized by naloxone-methiodide and nor-binaltorphimine, but not by cyprodime nor naltrindole, thus suggesting the involvement of peripheral kappa-opioid receptors. In conclusion, the stimulation of peripheral mu-, delta- and kappa-opioid receptors is a pharmacological strategy useful for relieving this experimental type of bone cancer-induced pain, the greatest analgesic effect being achieved by stimulating peripheral mu-opioid receptors. 1: Neurosci Lett. 2004 Apr 22;360(1-2):85-9. Links Local peripheral effects of mu-opioid receptor agonists in neuropathic pain in rats. Obara I, Przewlocki R, Przewlocka B. Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Kraków, Poland. Our study was designed to demonstrate peripheral antinociception of the mu-opioid receptor agonists: morphine (MF), [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]enkephalin (DAMGO), endomorphin-1 (EM-1) and endomorphin-2 (EM-2) in Bennett&apos;s rat model of neuropathic pain. All the agonists were effective in antagonizing allodynia after their intraplantar (i.pl.) but not subcutaneous (s.c.) administration. Opioid peptides: DAMGO, EM-1 and EM-2 were more effective compared with corresponding doses of morphine (opioid alkaloid) in alleviating chronic pain. Peripheral mu-opioid receptors mediated the observed effects, as was evidenced by the i.pl. treatment with naloxone methiodide (active only at the site of injection) and by cyprodime, a selective mu-opioid receptor antagonist. These results have shown that opioid peptides are effective also after local treatment, and that their peripheral use may be of therapeutic interest in long-term management of chronic pain. 1: Ann Neurol. 2003 Mar;53(3):366-75. Links Mu opioid receptors and analgesia at the site of a peripheral nerve injury. Truong W, Cheng C, Xu QG, Li XQ, Zochodne DW. Department of Clinical Neurosciences and the Neuroscience Research Group, University of Calgary, Calgary, Alberta, Canada. Opioid ligands may exert antinociception through receptors expressed on peripheral afferent axons. Whether local opioid receptors might attenuate neuropathic pain is uncertain. In this work, we examined the function and expression of local mu opioid receptors (MORs) associated with the chronic constriction injury (CCI) model of sciatic neuropathic pain in rats. Low-dose morphine or its carrier were percutaneously superfused over the CCI site with the injector blinded to the identity of the injectate. Morphine, but not its carrier, and not equimolar systemic doses of morphine reversed thermal hyperalgesia in a dose-related, naloxone-sensitive fashion. Moreover, analgesia was conferred at both 48 hours and 14 days after CCI, times associated with very different stages of nerve repair. Equimolar local DAGO ([D-Ala2, N-Me-Phe4, Gly5-(ol)] enkephalin), a selective MOR ligand, provided similar analgesia. Local morphine also attenuated mechanical allodynia. MOR protein was expressed in axonal endbulbs of Cajal just proximal to the injury site, in aberrantly regenerating small axons in the epineurial sheath around the CCI site and in residual small axons distal to the CCI lesion. Sensory neurons ipsilateral to CCI had an increase in the proportion of neurons expressing MOR. We suggest that local MOR expressed in axons may be exploited to modulate some forms of neuropathic pain. : Psychopharmacology (Berl). 2000 Feb;148(2):180-5. Links Local administration of mu or kappa opioid agonists attenuates capsaicin-induced thermal hyperalgesia via peripheral opioid receptors in rats. Ko MC, Tuchman JE, Johnson MD, Wiesenauer K, Woods JH. Department of Pharmacology, University of Michigan Medical School, 1301 MSRB III, Ann Arbor, MI 48109-0632, USA. RATIONALE: By acting on peripheral opioid receptors, opioid agonists can attenuate nociceptive responses induced by a variety of agents. OBJECTIVES: This study was conducted to characterize capsaicin-induced thermal hyperalgesia in rats and to evaluate the hypothesis that local administration of either mu or kappa opioid agonists (fentanyl and U50,488, respectively) can attenuate capsaicin-induced nociception. METHODS: Capsaicin was administered s. c. in the tail of rats to evoke a nociceptive response, which was measured by the warm-water tail-withdrawal procedure. Either fentanyl or U50,488 was co-administered with capsaicin in the tail to evaluate local antinociceptive effects. In addition, the local antagonism study was performed to confirm the site of action of both opioid agonists. RESULTS: Capsaicin (0.3-10 microg) dose dependently produced thermal hyperalgesia manifested as reduced tail-withdrawal latencies in 45 degrees C water. Co-administration of either fentanyl (0.32-3.2 microg) or U50,488 (10-100 microg) with capsaicin (3 microg) attenuated capsaicin-induced hyperalgesia in a dose-dependent manner. Furthermore, this local antinociception was antagonized by small doses (10-100 microg) of an opioid antagonist, quadazocine, applied s.c. in the tail. However, the locally effective doses of quadazocine, when applied s.c. in the back (i.e., around the scapular region), did not antagonize either fentanyl or U50,488. CONCLUSIONS: In this experimental pain model, activation of peripheral mu or kappa opioid receptors can attenuate capsaicin-induced thermal hyperalgesia in rats. It supports the notion that peripheral antinociception can be achieved by local administration of analgesics into the injured tissue without producing central side effects. 1: J Pharmacol Exp Ther. 1998 Jul;286(1):150-6. Links The role of peripheral mu opioid receptors in the modulation of capsaicin-induced thermal nociception in rhesus monkeys. Ko MC, Butelman ER, Woods JH. Department of Pharmacology, University of Michigan, Ann Arbor, USA. Capsaicin produces burning pain, followed by nociceptive responses, such as allodynia and hyperalgesia in humans and rodents. In the present study, when administered subcutaneously into the tail of rhesus monkeys, capsaicin (0.01-0.32 mg) dose-dependently produced thermal allodynia manifested as reduced tail-withdrawal latencies in 46 degrees C water, from a maximum value of 20 sec to approximately 2 sec. Coadministration of selective mu opioid agonists, fentanyl (0.003-0.1 mg) and (D-Ala2,N-Me-Phe4, Gly5-ol)-enkephalin (0.001-0.03 mg), dose-dependently inhibited capsaicin-induced allodynia. This local antinociception was antagonized by small doses of opioid antagonists, quadazocine (0.03 mg) and quaternary naltrexone (1 mg), applied locally in the tail. However, these doses of antagonists injected s.c. in the back did not antagonize local fentanyl. Comparing the relative potency of either agonist or antagonist after local and systemic administration confirmed that the site of action of locally applied mu opioid agonists is in the tail. These results provide evidence that activation of peripheral mu opioid receptors can diminish capsaicin-induced allodynia in primates. This experimental pain model could be a useful tool for evaluating peripherally acting antinociceptive agents without central side effects and enhance new approaches to the treatment of inflammatory pain.
Group I Local anesthetic + buprenorphine 0.3 mg + IM saline = 22.3 hours Group II Local anesthetic + IM buprenorphine 0.3 mg. = 23.5 hours Group III Local anesthetic + IM saline. = 6.6 hours Candido KD, Winnie AP, Ghaleb AH, Fattouh MW, Franco CD: Buprenorphine added to the local anesthetic for axillary brachial plexus block prolongs postoperative analgesia. Reg Anesth Pain Med. 2002 Mar-Apr;27(2):162-7
Histamine Hyperthermia cats hypo dogs Endocrine hypothyroidism/cushings Severely debilitate Head injuries Respiratory disease Severe renal insufficiency
Regional Anesthesia For Oral
Surgery In Dogs and Cats
DVM, FAVD, DAVDC
Diplomate, American Academy
of Pain Management
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Why Nerve Blocks for Oral Surgery?
J Pharmacol Exp Ther. 1998 Jul;286(1):150-6.
The role of peripheral mu opioid receptors in the modulation of
capsaicin-induced thermal nociception in rhesus monkeys.
Ko MC, Butelman ER, Woods JH.
Neurosci Lett. 2004 Apr 22;360(1-2):85-9.
Local peripheral effects of mu-opioid receptor agonists in
neuropathic pain in rats.
Obara I, Przewlocki R, Przewlocka B.
Anesthesiology. 1998 Jul;89(1):190-201.
Peripheral morphine administration blocks the development of
hyperalgesia and allodynia after bone damage in the rat.
Houghton AK, Valdez JG, Westlund KN.
Median duration of satisfactory analgesia:Median duration of satisfactory analgesia:
11.5 h (8-15) without an opioid11.5 h (8-15) without an opioid
21.0 h (9-27) with morphine21.0 h (9-27) with morphine
20.0 h (14-34) with buprenorphine20.0 h (14-34) with buprenorphine
Bazin JE, Massoni C, Bruelle P, Fenies V, Groslier D, Schoeffler P: The addition ofBazin JE, Massoni C, Bruelle P, Fenies V, Groslier D, Schoeffler P: The addition of
opioids to local anaesthetics in brachial plexus block: the comparative effects ofopioids to local anaesthetics in brachial plexus block: the comparative effects of
morphine, buprenorphine and sufentanil. Anaesthesia. 1997 Sep;52(9):858-62morphine, buprenorphine and sufentanil. Anaesthesia. 1997 Sep;52(9):858-62
Group IGroup I
Local anesthetic + buprenorphine 0.3 mg + IMLocal anesthetic + buprenorphine 0.3 mg + IM
Group IIGroup II
Local anesthetic + IM buprenorphine 0.3 mg.Local anesthetic + IM buprenorphine 0.3 mg.
Group IIIGroup III
Local anesthetic + IM saline.Local anesthetic + IM saline.
Candido KD, Winnie AP, Ghaleb AH, Fattouh MW, Franco CD: Buprenorphine added toCandido KD, Winnie AP, Ghaleb AH, Fattouh MW, Franco CD: Buprenorphine added to
the local anesthetic for axillary brachial plexus block prolongs postoperative analgesia.the local anesthetic for axillary brachial plexus block prolongs postoperative analgesia.
Reg Anesth Pain Med. 2002 Mar-Apr;27(2):162-7Reg Anesth Pain Med. 2002 Mar-Apr;27(2):162-7