Understanding postmastectomy and postthoracotomy pain mechanisms

PAIN NOCICEPTIVE AND
NEUROPATHIC MECHANISMS 0889-8537/97 $0.00 + .20
POSTMASTECTOMY AND
POSTTHORACOTOMY PAIN
Anne M. Wallace, MD, and Mark S. Wallace, MD
Surgical intervention into a soft tissue may lead to unavoidable injury to
muscle and fat masses, the development of scar tissues, local reactions to foreign
bodies (as may be employed in reconstruction), and lesions of sensory afferents
that traverse or terminate in the surgical region. These occurrences are character-
istics of most surgical procedures but apply with particular clarity to interven-
tions involving the breast and chest wall. Whether for reconstruction or for more
aggressive interventions related to removing tumor in cancer therapy, there are
documented insults to structure and innervation. In addition, the treatment for
malignancy may involve chemotherapy, known to induce peripheral neuropa-
thies, and the use of radiation. Such radiation, although targeted at the tumor,
may often unavoidably injure the underlying brachial plexus, leading to an
additional neuropathy. Despite this degree of intervention, it has not been
widely appreciated that pain may be a sequela of these treatments. Typically
the concern with tumor reoccurrence has left the problems related to the pain
resulting from these interventions largely unappreciated.
COMPARISON OF POSTMASTECTOMY AND
POSTTHORACOTOMY PAIN STATES
Because of the target area of the surgery, there is often a misconception
that postmastectomy pain is essentially the same as that described loosely as
postthoracotomy pain. Although certain components of the two pain states
overlap, they, in fact, reflect quite distinct syndromes. This article therefore
considers the incidence, cause, underlying mechanisms, and treatment for both
the postmastectomy and the postthoracotomy pain states.
From the Departments of General and Plastic Surgery (AMW),and Anesthesiology (MSW),
University of California, San Diego, La Jolla, California
~~~ ~~~ ~~~~~ ~
ANESTHESIOLOGY CLINICS OF NORTH AMERICA
VOLUME 15-NUMBER 2 -JUNE 1997 353

354 WALLACE & WALLACE
POSTMASTECTOMY PAIN
One in eight women develops breast cancer. In the absence of metastasis, a
small percentage (approximately 6%) of these women present with breast pain
as a primary omp plaint.'^^ In the face of frank metastasis to bone and soft tissue,
the incidence of pain in the site of metastasis is virtually 100%. Of women
diagnosed with cancer, roughly 60% are treated with mastectomy as a curative
procedure, with or without surgical reconstruction? Although cure of disease is
of overriding importance, some of these women, once surgically treated, are left
with an ill-defined postmastectomy pain syndrome. Four percent to 14% of
women suffer postmastectomy pain? 41, 49, 119, although it may be as high as
31%.105,117 This suggests that in a population of 250 million, a large population
of women suffer significant pain secondary to the treatment of breast cancer;
conservatively, approximately 500,000 to 2.5 million women may be so afflicted,
suggesting the potential magnitude of this problem.
The onset of postmastectomy pain ranges from 2 weeks to 6 months.
Moreover, 23% to 100°/~report abnormal sensation in the axilla and medial
aspect of the arm. The pain described ranges from mild to intractable and
disabling. A study by Wallace and colleagues117showed that in its most florid
presentation the pain was frequently persistent and characterized in those so
afflicted with several components, including a general burning, aching sensation
referred to the tissue region underlying the mastectomy in the axilla, medial
upper arm, or chest and paroxysmal episodes of shooting and lancinating pain.
In addition, following mastectomy, 10% to 64% of women report phantom breast
sensations, with the majority of women noticing the phantom breast within 1
week.', 6 ~ 6 ~Of women reporting phantom breast sensations, 80% are painful.%
The nature of the pain state just described results in a significant impairmentin
the ability to perform daily occupational activities. These numbers represent
many women whose quality of life is notably impaired, despite adequate treat-
ment of their breast cancer.
Innervation of the Breast
The innervation of the breast and surrounding tissue is intricate in its
association with the brachial plexus.104As indicated schematically in Figure 1,
the long thoracic nerve arises from the roots of C5, C6, and C7 and innervates
the serratus anterior muscle. The thoracodorsal nerve from C6 innervates the
latissimus dorsi muscle. Injury to either of these nerves may occur because of
vigorous traction during modified radical mastectomy, even though they are
routinely 69 The innervation of the pectoralis major and minor muscles
is via the lateral and medial pectoral nerves, although there is some variability
over which nerve innervates which muscle. These nerves arise as roots from the
lateral (C5-C7)and medial (C8 T1) cords of the brachial plexus.
Innervation of the skin of the breast comes from the third through the sixth
intercostal nerves (Fig.2). The anterior end of these nerves turns superficiallyas
the anterior cutaneous nerves and, passing through the sternal intercostal space,
penetrate the muscle and divide into short medial cutaneous branches. These
branches go to the midline of the body, whereas longer lateral branches extend
to the nipple line. These branches essentially innervate the medial half of the
breast and as such are called the medial mammary branches (see Fig. 3). Each
intercostal nerve after the second also gives off a lateral cutaneous nerve. The

POSTMASTECTOMYAND POSTTHORACOTOMYPAIN 355
Medialpectoral nerveto the
pectoralis minor muscle
Lateral pectoral nerve to the
pectoraiis major muscle
Longthoracic nerve to the
serratus anterior muscle
Thoracodorsal nerve to the
latissimus dorsi muscle Breast
Figure 1. The origin of innervation of musculature around the breast. Medial and lateral
pectoral nerves arise from the brachial plexus and course to their respective muscles
(pectoralis minor and major). The long thoracic nerve arises from the brachial plexus and
courses down the medial axilla and down lateral chest wall to innervate the serratus anterior
muscle. The thoracodorsal nerve arises from the posterior cord of the brachial plexus and
courses in the posterior aspect of the axilla and down the posterolateral chest wall to
innervate the latissimus dorsi muscle. All of these nerves carry postganglionic sympathetic
fibers originating from the stellate and middle cervical ganglion. Damage to these nerves
during mastectomy may result in neuropathic pain. Also note the close relationship of the
breast and axilla to the brachial plexus. Radiation to the breast and axilla may damage
nerves described here as well as the brachial plexus.
well-described intercostobrachial nerve is the equivalent branch of the second
intercostal nerve (Fig. 2).lZ1
The lateral branches divide into anterior and posterior branches to innervate
further the rest of the breast (Fig. 3). Although it is routinely thought that the
anterior branch of the fourth lateral cutaneous nerve is the single nerve to the
there is a great deal of variation as to where the medial and lateral
branches unite. It is therefore not possible always to predict whether the innerva-
tion of the nipple and areola comes from the medial or lateral mammary nerves
or is shared by both.24,3b,78,'I2 Again, these are important factors when consider-
ing breast-sparing surgery in which the nipple is maintained.
Pathogenesisof Postmastectomy Pain
Postmastectomy pain is a complex problem that likely has a number of
contributing causes. The syndrome has long been thought to have a significant

T2
Figure 2. Cutaneous and glandular innervationof the breast and axilla. Innervation of the
breast arises from intercostal nerves 3-6. Innervation of the nipple is from the fourth
intercostal nerve. The intercostobrachial nerve arises from the second intercostal nelve
and courses through the superficialaxilla to innervatethe axilla and skin of the upper arm.
All of these nerves may be injured during mastectomy, which may leadto neuropathicpain.
psychological component. The patient must recover from a type of ablative
surgery, with all its sequelae, suffer a major impact on body image, and muster
the emotional and psychological resources to fight against cancer. Accordingly,
the underlying physiologic component to the pain state may be overlooked in
the thinking that much of its cause is psychological. To enhance the knowledge
of postmastectomy pain (and that caused, or exacerbated, by reconstruction),a
basic understanding of its origin must be obtained. The sources of the pain
associated with breast surgery and secondary to cancer may arise from a number
of sources. These sources may be broadly divided into states that are secondary
to tissue injury (see the article by Sorkin) or nerve injury (see the article by
Yaksh and Chaplan).
Tissue injury
An obvious acute source of pain arises from the common problems associ-
ated with tissue injury, secondary to the surgical procedure. After recovery from
the surgery, pain associated with a somatic origin may arise as a result of tumor
returrence. Tumor invasion of the ribs causes well-known bone pain.
Mechanisms of the pain from rib metastasis include (1)release of algesio-
genic substances (prostaglandins, bradykinin, substance P, histamine) from the

POSRvIASTECTOMYAND POSTTHORACOTOMY PAIN 357
Internal intercostal muscle
External intercostal muscle.
muscle
Collateral branch
Intercostal nerve
Lateralcutaneous w- Transversalismuscle
branch
Serratusanterior
muscle
Pectoralis minor muscle
Pectoralis major muscle
branchv
Figure 3. Nerves and muscles of the thoracic wail. The thickness of intercostal muscles is
exaggerated. The breast receives innervation from the lateral cutaneous and anterior
cutaneous branch of intercostal nerves 3-6.
damaged bone tissue, which stimulates the nerve endings of the endosteum; (2)
stretching of the periosteum by increasing tumor size; and (3)fracture (see the
article by Sorkin).lo,85, 9R
Nerve Injury
The verbal descriptors employed in a significant proportion of the postmas-
tectomy pain patient (including lancinating and shooting) bear significant simi-
larity to those employed by patients suffering from pain secondary to evident
nerve injury (see the article by Yaksh and Chaplan). In addition to the clear
parallels with neuropathic sensations, a less frequent observation after mastec-
tomy is phantom breast pain. The low incidence may be explained by the fact
that breasts, in contrast to limbs, do not mediate kinesthetic sensory impulses,
which, together with kinetic and exteroceptive sensations, constitute the phan-
tom-related phen~menon?~,99 Another explanation of the relatively low inci-
dence of phantom breast syndrome could be that the somatosensory cortical
area that represents the breast is relatively Because the nipple has the
richest nerve supply, phantoms are most related to this area. If premastectomy
pain is present, there is a higher incidence of phantom breast pain.I0
Origins of Nerve Injury
Nerve injury after mastectomy may arise from several sources.
Surgical Insult.Mastectomy may necessitate section of nerves that innervate
the lesioned region. In addition, several nerves typically undergo mechanical

injury in breast surgery. The innervation of the pectoralis muscles via the
lateral and medial pectoral nerves may be injured during mastectomy (owingto
traction or scarring), despite sparing adjacent muscle or fascia.”
The intercostobrachial nerve has been reportedly injured in 80% to 100%
of mastectomy patients undergoing axillary dissection and has been described
as the cause of the axillary and upper arm pain from which these women suf-
Nonsurgical Insult. Several nonsurgical causes of nerve injury also exist.
(1) Radiation after surgical therapy may enhance or cause a pain syndrome.
Severity and time of onset are proportional to total dose in animals and hu-
m a n ~ . ~ ~ ,m, Importantly, many of these effects may appear with considerable
delay after even low-dose radiation.46,88 As indicated in Figure 1, the radiation
exposure to the axilla essentially encompasses not only the local innervation,
but also the cords of the brachial plexus. (2) Chemotherapy commonly used for
breast cancer, such as the t a x o l ~ ~ l , ~ ~and the vinca alkaloids48as well as a variety
of combination protocols employing several agents including cisplatin and
methotre~ate,~~,Io3 is appreciated to induce neuropathic states. Such neuropathies
are frequently characterized by a stocking-and-glove syndrome common to
systemic chemical peripheral neurotoxicity. Importantly, there appears to be an
enhancement of the neuropathic effects of radiation and chemotherapy.p6The
mechanisms of these neurotoxicities are multiple but likely reflect on the ability
of many of these agents to influence microtubules and neurofilaments and
accordingly alter axon transport. (3) Fibrosis of the surrounding connective
tissue results in local constrictive and compressive forces, which can lead to
secondary nerve injury.” (4) Finally, metastasis can lead to space-occupying
masses that can result in a chronic nerve compression syndrome. Such compres-
sion can alter vascular perfusion and increase endoneureal pressure leading to
loss of nerve function. This may progress to total nerve tissue destruction and
may involve the brachial plexus.
fer,32. 60,87, 115
POSTrHORACOTOMYPAIN
In the immediate postoperative period after thoracic surgery, severe pain
may be reported in as much as 70% of the patient pop~lation.~~The majority of
these patients have a complete resolution of the pain within an interval of days
as in other postoperative pain states. A significant number of patients, however,
experience long-term postthoracotomy pain. Reports on the incidence of chronic
postthoracotomy pain at 6 months have ranged from 26% to 67%.2”5y, 65, 71 Of the
patients with persistent pain, 9% to 66% require medical intervention, and many
are refractory to therapy?5,59, ffi, 71 As with postmastectomy pain, causes of
postthoracotomy pain may be broadly divided into states that are secondaryto
tissue injury (see the article by Sorkin) or nerve injury (see the article by Yaksh
and Chaplan).
Pathogenesis
Somatic Pain-Tissue Injury
Myofascial Pain. Myofascial pain is among the more frequent causes of
severe disabling pain. Postthoracotomy patients may suffer from this syndrome.
There are several possible mechanisms leading to myofascial pain in this group

POSTMASTECTOMY AND POSTTHORACOTOMYPAIN 359
of patients. The intercostal neuralgia and scar pain previously described may be
exacerbated by movement; therefore, the patient limits movement. It has been
demonstrated that sedentary patients are more likely to develop myofascial pain
than patients who exercise regularly.1m,'01 Limitation of movement in these
patients may contribute to myofascial pain. CailletI4proposed that trigger points
are caused by the presence of blood and extracellular material that are not
reabsorbed after soft tissue damage. This results in adhesions that limit the
gliding action of muscles, resulting in tension and spasms. Prolonged tension
and spasm within the muscle can cause muscle fatigue and local ischemia,
which stimulates the release of algesiogenic agents, such as histamine, kinins,
and prostaglandin^.'^^ These algesiogenic substances may stimulate further pain
and spasm leading to a vicious cycle.
Because of their location, the intercostal and serratus anterior muscles are
likely to be damaged during a thoracotomy. Other muscles that may be damaged
include the pectoralis major and minor, latissmus dorsi, levator scapulae, and
teres major and minor.84Indeed, the serratus anterior muscle is likely to be
involved in postthoracotomy pain because it has been demonstrated that block-
ade of the long thoracic nerve (which supplies this muscle) relieves the pain
in some patients?z Also, denervation of a muscle may lead to denervation
hypersensitivity.This can lead to a supersensitivity of the muscle to biochemical
agents and nerve impulses.*,17, 51, claims that trigger points may
develop in muscles as a result of this denervation hypersensitivity.
Tumor Recurrence. Postthoracotomy pain may also be the result of direct
tumor invasion. Tumor invasion of the bone is the most common cause of
pain from metastatic disease followed by tumor compression or infiltration of
peripheral nerves or plexuses.40Bronchial carcinoma may metastasize to the
chest wall and involve the ribs and intercostal nerves. The pain of rib metastasis
can be confused with postthoracotomy pain as described earlier. The pain
associated with recurrence may, however, be initially constant and aching with-
out the hyperpathia associated with peripheral nerve damage. The mechanisms
of bone pain described for postmastectomy pain also apply for postthoracot-
omy pain.
Neuropathic Pain
The pain resulting from intercostal nerve damage appears no different from
the neuropathic syndrome typically associated with a peripheral nerve injury
(see the article by Yaksh and Chaplan). The pain is felt in the region of sensory
deficit (if present), and there may be a delay of weeks to months between the
thoracotomy and onset of the pain. The pain is described as dysesthetic and
burning with a superimposed shooting component that appears episodically
and persists for seconds to minutes. Frequently, allodynia, a painful sensation
evoked by a low-threshold mechanical stimulus, can be demonstrated in the
painful area.38
Nerve Damage
As in mastectomy pain states, the origin of the injury to thoracic nerves
may be varied.
Surgical Insult. Because of their location in the intercostal space, intercostal
nerves are susceptible to surgical trauma (see Figs. 2 and 3).Rib retraction can
partially damage the nerve, and a misplaced suture can cause a chronic nerve
compression resulting in pain associated with a wide range of sensory deficits.

360 WALLACE &WALLACE
Rib resection transects the nerve and leads by definition to deafferentation (loss
of sensory input). All such interventions can lead to intercostal neuralgias,but
rib resection appears to have a higher incidence.53,54 Overall, the incidence of
postthoracotomy neuralgia ranges from 1%to 15%. 21-23, 53, 54, 59 Surgical tech-
niques using rib retraction cause a 1%to 8% incidence:'-23, 53, 54, 59 and the
incidence of neuralgias with rib resection approaches 10% to 15%.",54
Pain within the postthoracotomy scar can cause significant discomfort to
the patient. The incidence of postthoracotomy scar pain is unknown, but the
incidence after mastectomy has been estimated to be between 23% and 35%."
Usually, patients with painful scars present with trigger points rather than
diffuse pain in the entire scar. These trigger points are most likely the result of
microcompression of small nerves or microneuromas that develop within the
scar.", 27 Histologic examination of scar tissue has revealed numerous demyeli-
ated axons and neur0rnas.3~Thus, the pathophysiology of these microcompres-
sions and microneuromas follow the discussion presented earlier in this article.
Continuous burning and aching pain extending beyond the immediate area of
the scar is most likely due to an intercostal nerve injury.
Although unusual, some patients may complain of constant itchiness and
pain in the scar. Nara*' demonstrated that patients with this complaint had
elevated levels of histamine and serotonin within the scar tissue. Histamine is
released from mast cells, and serotonin is released from platelets secondaryto
tissue trauma. Both substances have been demonstrated to stimulate peripheral
nociceptors.6,64
Nonsurgical Insults. A variety of nonsurgical mechanisms may lead to
injured thoracic nerves, including (1)fractured ribs, which can result in an acute
mechanical compression of the intercostal nerve resulting in a sharp neuralgic
pain radiating into the distribution of the injured nerve, (2) increased tumor
size, which may lead to a compression neuropathy, and the eventual infiltration
of the nerve, which leads to total destruction and the development of the
deafferentation pain.
Superior pulmonary sulcus tumors may compress or infiltrate the lower
brachial plexus resulting in Pancoast's syndrome. This syndrome produces pain
in the shoulder, scapula, and posterior aspect of the arm and elbow. The
mechanism behind the pain of this syndrome is similar to peripheral nerve
injury, although a significant number of these patients develop classic causalgia
of the upper extremity." Therefore, initially a pain caused by peripheral mecha-
nisms may progress to central mechanisms."
TREATMENT
Because of the similar causes behind postmastectomy and postthoracotomy
pain, treatment, at present, is similar.
Neural Blockade
Sympathetic or somatic blockade in conjunction with the tricyclic antide-
pressants may be tried. These neural blockades can be achieved by intercostal
nerve blocks, thoracic sympathetic block, stellate ganglion block (if a high
enough volume is used to reach the thoracic sympathetic chain), or epidural
blockade. There is much controversy over the value of repeated neural blockade
in the treatment of sympathetically mediated pain. Although controversial,

POSTMASTECTOMY AND POS'ITHORACOTOMYPAIN 361
sympathetic or neural blockade performed early in the course of the pain may
be helpful. Many women with postmastectomy pain develop frozen shoulders.
At the least, early intervention provides pain relief necessary for aggressive
physical therapy to be employed. If pain relief can be achieved with neural
blockade, this should always be pursued in conjunction with a physical therapy
program. The neural blockade performed early thus not only enhances physical
therapy, but also may prevent central changes that may occur in the dorsal horn
as a result of the pain.
Tricyclic Antidepressants
The tricyclic antidepressants have been proven useful in a variety of neuro-
pathic pain syndromes, especially when the pain has a prominent dysesthetic
or burning quality,13Although patients suffering from postmastectomy and
postthoracotomy pain may be depressed secondary to the pain and the fact that
they are facing cancer, the tricyclics seem to have analgesic properties indepen-
dent of their antidepressant properties.118,lZo Furthermore, the analgesia from the
tricyclics occurs at a lower dose than required for the antidepressant 118
The inhibition of the uptake of norepinephrine and serotonin into nerve termi-
nals of the central nervous system forms the basis of the analgesia seen with
tricyclic antidepressants. Brain stem serotoninergic and noradrenergic neurons
project to the spinal dorsal horn, where they modulate incoming nociceptive
transmission. Thus, the tricyclics may stimulate these brain stem neurons to
block incoming pain impulses into the spinal dorsal horn.37Studies have sug-
gested that at least some of the tricyclic antidepressants may function as antago-
nists of the N-methyl-D-asparate (NMDA)receptor. NMDA receptor antagonists
have been described in preclinical and limited clinical models as being effective
in certain neuropathic pain states.
a-Adrenoceptor Agents
If peripheral nerve injury is considered as the cause of the pain, it is
reasonable to hypothesize that the pain may have a sympathetically mediated
component. Damaged peripheral nerves form axonal sprouts and occasionally
neuromas, which may be activated by norepinephrine. An intravenous phentol-
amine challenge is a simple procedure that determines if the pain is sympatheti-
cally mediated.y1Because of the complex innervation of the breast and chest
wall, isolated sympathetic blockade may prove difficult and further supports a
phentolamine challenge as the initial treatment to avoid a false-negativediagno-
sis. Once sympathetically mediated pain is diagnosed, several approaches may
be taken.
There are few systematic studies on the use of adrenoceptor agonists or
antagonists on the postmastectomy and postthoracotomy pain state. The mecha-
nism behind sympathetic and somatic blockade is a decrease in sympathetic
outflow and thus decreased release of active factors from sympathetic nerve
terminals, which can otherwise stimulate sensitized nerve endings, neuromas,
or dorsal root ganglion cells.72,y4, 97 It is conceivable that spinal a,-agonists,
because of their sympatholytic action on preganglionic neurons,34,45 could pro-
vide pain relief in these patients by a similar mechanism. Studies have demon-
strated that spinal a,-agonists suppress neuropathic pain in animalsy0,Iz7 and
reflex sympathetic dystrophy (RSD) in h~mans.9~It has also been demonstrated

in humans that topical clonidine relieves the hyperalgesia in patients with
sympathetically maintained painz6This is believed to reflect a presynaptic effect
of clonidine in the sympathetic terminals in the vicinity of the site of application.
Although neural blockade and a,-agonists reduce peripheral catecholamine
release, the available oral adrenolytic agents block the a,-receptors, which have
been implicated in mediating sympathetic pain?6 Prazosin and phenoxybenza-
mine have effectively relieved the pain of causalgia; therefore, it is reasonable
to assume that these agents would be beneficial in postmastectomy pain.
Sodium Channel Blockers
A logical step is a trial of systemic local anesthetics. Long-term therapy is
best accomplished with oral sodium channel blockers (i.e., antiarrhythmics,
anticonvulsants) because lidocaine is not active following oral administration.
Long-term oral sodium channel blocker therapy is not without risk, and it is
reasonable before embarking on such treatment to attempt identification of those
patients who would benefit from these agents. A lidocaine challenge is a simple
test used to determine if the pain is sensitive to sodium channel blockers. This
test is performed by infusing up to 5 mg/kg of lidocaine intravenously over 30
to 45 minutes? End points to infusion are a 50% reduction in pain or unaccept-
able side effects, such as tinnitus, dizziness, nausea, or muscle twitching.These
signs prelude seizure activity and should be watched for and the infusion
discontinued if present.
The effects of lidocaine on afferent processing are complex. In brief, preclini-
cal studies have shown that in order of decreasing sensitivity (higher plasma
levels), lidocaine (1)blocks spontaneous activity in neuroma, (2) blocks sponta-
neous activity in ganglion of injured axon, (3) blocks spinal activity evoked by
protracted C fiber discharge (centralfacilitation),(4) blocks activity evoked in C fi-
ber by local tissue injury, and (5) blocks conduction in uninjured a x 0 n . 2 ~ ~ ~ ~ ~ ~ ~ ~ ~
Mexiletine, a sodium channel blocker in the same class of medications as lido-
caine, is available in an oral preparation and has been used to treat chronic
neuropathic pain ~tates.'~,28, Io6, As noted previously, intravenous lidocaine
does not seem to suppress C fiber activity because limb ischemic pain, which
selectively blocks large and small myelinated fibers, is not relieved by
lidocaine.8,95 If the pain is sensitive to lidocaine, oral sodium channel blockers
can be started and the dose gradually increased until pain relief is achieved or
the maximum daily dose is reached.Io6
With the discovery that anticonvulsants successfullytreat trigeminal neural-
gia, this class of drug has found a place in the treatment of neuropathic pain
with a shooting c~mponent.~Swerdlow and CundilPo7determined that lancinat-
ing pain could be treated with a number of anticonvulsant drugs, including
phenytoin, carbamazepine, clonazepam, and valproic acid. Carbamazepine has
become the anticonvulsant of choice with phenytoin following a close second.
The new anticonvulsant, gabapentin, however, may replace the older anticonvul-
sants because of the extremely low side-effect profile.80This new agent has been
reported to be effective in the treatment of reflex sympathetic dystr0phy.7~.15
The mechanism behind the pain relief of anticonvulsants is thought to be
similar to local anesthetics. Phenytoin and carbamazepine block voltage-sensitive
sodium channels, which probably explains their pain relief in this class of
patients. Carbamazepine causes the greatest inhibition.18The exact mechanism

POSTMASTECTOMY AND POSTTHORACOTOMYPAIN 363
of gabapentin is unknown. Although it has a y-aminobutyric acid (GABA)-like
structure, it does not appear act on the GABA receptor.74,75
Phenothiazines
The use of phenothiazines alone in chronic pain is controversial, although
they are used frequently in combination with opioids for chronic pain. There is
evidence in animal studies that dopaminergic systems are involved in pain
modulation.63,lz8 The phenothiazines have been reported to be effective in the
treatment of a variety of peripheral neuropathies, including diabetic neuropathy
and postherpetic ne~ralgia.3~.52,70,83 Therefore, it seems a reasonable approach to
try this class of drugs if other treatments fail.
Opioids and Nonsteroidal Anti-Inflammatory Drugs
In general, the opioids and nonsteroidal anti-inflammatory drugs (NSAIDs)
are not effective in treating pain secondary to nerve injury. The dysesthesia and
allodynia observed in postmastectomy and postthoracotomy pain is thought to
be mediated through large myelinated afferents that activate sensitized nocicep-
tors within the central nervous ~ystem.’~,l6 This phenomenon explains the low
efficacy of the opioids in peripheral nerve injury pain. The opioids are thought
to act presynaptically to inhibit the release of substance P from unmyelinated
fibers in the dorsal horn.2O They do not inhibit input of the large myelinated
afferentsand therefore cannot affect the allodynia mediated by these fibers. The
opioids also act on supraspinal receptors, however, which activate descending
inhibitorycontrol on nociception.126This mechanism of action may provide some
pain relief in these patients.
Through the cyclooxygenase system, tissue damage and inflammation re-
sults in the release of prostaglandins, which activate or sensitize high-threshold
unmyelinated fibers.42.85 Repetitive small afferent activation can lead to the
release of prostanoids from the spinal cord, where they are believed to facilitate
central nociceptive processing leading to a concurrent, spinally mediated facilita-
tion. Dysesthesias and allodynia, however, usually persist long after the in-
flammationhas subsided. Therefore,NSAIDs may become less effective because
the unmyelinated fibers become less important in modulating the pain in these
patients. Although the opioids and NSAIDs are ineffective in peripheral nerve
injury, they can be effective in pain originating from tissue damage and inflam-
mation, such as rib infiltration of tumor and rib fracture.
Trigger Point Injections
If the postmastectomy or postthoracotomy pain is myofascial in origin,
discrete trigger points can usually be identified in the muscles of the thorax
distant from the site of nerve injury. Referred pain is secondary to the trigger
points, and treatment should be directed to the latter. As discussed earlier,
myofascial pain is believed to reflect a somatic reflex cycle, which can be
interrupted. This can be accomplished by trigger point injections with local
anesthetic or spraying the skin overlying the trigger point with a vapor coolant.
These treatments are rarely of benefit when done alone, and it is necessary to
combine this treatment with stretching of the affected muscle.114If the myofascial

364 WALLACE 81 WALLACE
pain is determined to be located in the serratus anterior muscle, blockade of th
long thoracic nerve has been demonstrated to relieve the spasm."2 Intercost&
nerve blocks may also be performed to relieve spasms of the intercostal muscles
NeurostimulatoryTechniques
A conservative approach to postmastectomy and postthoracotomy pain
is transcutaneous electrical nerve stimulation (TENS). Several studies have
reported this technique to be the most successful after peripheral nerve
injury.9,67, 76 One study specifically stated that peripheral nerve injury pain
that is sympathetically mediated responds the best to TENS? Although the
mechanism of TENS analgesia is poorly understood, high-frequency and low-
intensity stimulation is thought to exert its analgesia through selective activation
of large myelinated afferents, which inhibit dorsal horn pain transmission.",lZ
In contrast, high-intensity and low-frequency stimulation produces analgesia
that is prolonged and naloxone reversible.Iu Thus, the latter technique most
likely stimulates both large and small myelinated afferents. As mentioned ear-
lier, injury to the intercostobrachial nerve may result in loss of large and small
myelinated afferents and thus loss of the inhibitory control these fibers exert.By
stimulating the remaining large myelinated afferents, analgesia may be pro-
vided. The issue of allodynia mediated by large afferents after nerve injury
suggests the mechanism of the disorder or the therapy is inadequately under-
stood.
Dorsal column stimulation (DCS) has gained widespread acceptance as a
pain-relieving technique since its introduction by Shealy and colleagueslo2in
1967.The burning dysesthetic pain of postthoracotomy patients is fairly localized
and therefore should be amenable to DCS. DCS has proved efficacious in
deafferentation pain of peripheral origin and postherpetic neuralgia.", 96 The
mechanism behind DCS is similar to TENS. Instead of stimulating large myelin-
ated primary afferents directly, however, large myelinated afferentsof the dorsal
columns are stimulated and antidromically activate large myelinated primary
afferent terminals in the dorsal horn.1° Animal studies have demonstrated that
DCS segmentally inhibits wide dynamic range neurons.Iz3
Neurolysis
Peripheral and central neurolysis should be reserved for patients with a
short life expectancy because of the high risk of neuralgia from this
procedure.Z1,23Cryoablation of the second or third intercostal nerve may be used
and has been demonstrated effective in the management of postthoracotomy
66 Dorsal root entry zone lesions have been reported effective for
deafferentation pain following peripheral nerve injury, but because of the inva-
siveness of this procedure, it should be one of last 44 The successof this
procedure seems greatest with nerve root avulsions and spinal cord injury.
Lower success rates have been found after more peripheral nerve injury. Avul-
sion rhizotomies and spinal cord injuries are associated with spontaneous activ-
ity of second-order neurons .within the dorsal horn, whereas peripheral lesions
cause spontaneous activity of the peripheral nerve and dorsal root ganglion."
Dorsal root entry zone lesions are directed at the hyperexcitable second-orde
neurons, thus explaining the higher success in more central nerve lesions.

POSTMASTECTOMYAND POSTTHORACOTOMY PAIN 365
Therefore, dorsal root entry zone lesions are less likely to be of any benefit in
this group of pain patients.
CONCLUSION
After mastectomy or thoracotomy, a complex pattern of pain may evolve.
Although there are some parallels in mechanism, this article emphasizes that
one syndrome is not the other. The cause of both syndromes emphasizes the
complexity of the state with a high likelihood that the pain may reflect not only
the common sequelae of surgical interventions, including tissue injury and
healing, but also nerve section. In addition, nerve injury may additionally derive
from the insults that occur secondary to the therapy targeted at the underlying
disorder (typically metastatic cancer). These insults jointly can induce a n im-
portant neuropathic condition that likely has an impact on the modest effects
that are possessed in these states for agents such as morphine. Consistent with
an important role for nerve injury in both pain states is the observation that a
number of agents, including systemic local anesthetics may be effective in these
conditions. The evolving understanding of the mechanisms underlying these
neuropathic states suggest that they might find an important use in the debilitat-
ing conditions.
References
1. Aitken DR, Minton JP: Complications associated with mastectomy. Surg Clin North
2. American Cancer Society: Cancer Facts and Figures. Atlanta, American Cancer Soci-
3. Assa J: The intercostobrachial nerve in radical mastectomy. J Surg Oncol 6123-126,
4. Axelsson J, Thesleff S A study of supersensitivity in denervated mammalian skeletal
5. Bach FW, Jensen TS, Kastrup J, et al: The effect of intravenous lidocaine on nociceptive
6. Beck PW, Handwerker H O Bradykinin and serotonin effects on various types of
7. Bergouignan M: Successfulcure of essential facial neuralgias by sodium diphenylhy-
8. Boas RA, Covino BG, Shahnarian A. Analgesic responses to IV lignocaine. Br J
9. Bohm E: Transcutaneous electrical nerve stimulation in chronic pain after peripheral
10. Bonica JJ:Anatomic and physiologic basis of nociception and pain. In Bonica JJ (ed):
11. Bonica JJ, Buckley FP: Cancer pain. In Bonica JJ (ed): The Management of Pain, ed 2,
12. Bonica JJ,BuckleyFP: Regional analgesia with local anesthetics. In Bonica JJ (ed):The
13. Bruera E, Ripamonti C: Adjuvants to opioid analgesics. In Patt RB (ed):Cancer Pain.
14. Caillet R Soft Tissue Pain and Disability. Philadelphia, FA Davis, 1977
15. Campbell JN, Raja SN, Meyer RA, et al: Myelinated afferents signal the hyperalgesia
16. Campbell JN, Raja SN, Meyer RA, et al: Myelinated afferents signal the hyperalgesia
Am 63:1331-1352, 1983
ety, 1992
1974
muscle. J Physiol 174:178, 1959
processing in diabetic neuropathy. Pain 40:29-34, 1990
cutaneous nerve fibers. Pflugers Arch 347209-222, 1974
dantoinate. Rev Laryngol Otol Rhiiol (Bord) 63:34-41, 1942
Anaesth 54:501-505, 1982
nerve injury. Acta Neurochir 40:277-285, 1978
The Management of Pain, ed 2. Philadelphia, Lea & Febiger, 1990, pp 28-94
Philadelphia, Lea & Febiger, 1990, pp 400-460
Management of Pain, ed 2. Philadelphia, Lea & Febiger, 1990, pp 1883-1966
Philadelphia,JB Lippincott, 1993, pp 143-159
associated with nerve injury. Pain 32:89-94, 1988
associated with nerve injury. Pain 32:89-94, 1988

17. Cannon WB, Rosenblueth A. The Supersensitivity of Denervated Structures. New
York, Macmillan, 1949
18. Catterall WA, Ragsdale DS, McPhee JC, et al: Common molecular determinantsof
local anesthetic antiarrythmic, and anticonvulsant block of voltage-gated Na + c h -
nels. Proceedings of the Na' Channels. Proceedings of the National Academy of
Sciences of the United States of America 93:9270-9275, 1996
19. Chabal C, Jacobson L, Mariano A, et al: The use of oral mexiletine for the treatment
of pain after peripheral nerve injury. Anesthesiology 76:513-517, 1992
20. Chang HM, Berde CB, Holz GG, et a1 Sufentanil, morphine, metenkephali, and
kappa-agonists (U-50,488H) inhibit substance P release from primary sensory neu-
rons: A model for presynaptic spinal opioid actions. Anesthesiology 70672677,1989
21. Conacher ID: Percutaneous cryotherapy for post-thoracotomy neuralgia. Pain 25227-
228, 1986
22. Conacher ID: Therapists and therapies for post-thoracotomy neuralgias. Pain 48409-
412, 1992
23. Conacher ID, Locke T, Hilton C: Neuralgias after cryoanalgesia for thoracotom!
Lancet 1:277, 1986
24. Cowie AT: Overview of the mammary gland. J Invest Dermatol 63:2-9, 1974
25. Dajczman E, Gordon A, Kreisman H, et a1 Long-term postthoracotomy pain. Chest
26. Davis KD, Treede RD, Raja SN, et al: Topical application of clonidine relieves
hyperalgesia in patients with sympathetically maintained pain. Pain 47:309-317,1991
27. Defalque RJ, Bromley JJ: Poststemotomy neuralgia: A new pain syndrome. Anesth
Analg 698142, 1989
28. Dejgard A, Petersen P, Kastrup J: Mexiletinefor treatment of chronic painful neuropa-
thy. Lancet Jan 29, 1988
29. deJong RH, Nace RA. Nerve impulse conduction during intravenous lidocaine
injection. Anesthesiology 29:22-28, 1968
30. Devor M, Wall PD, Catalan N: Systemic lidocaine silences ectopic neuroma and DRG
discharge without blocking nerve conduction. Pain 48:261-268, 1992
31. Dieras V, Marty M, Tubiana N, et al: Phase I1 randomized study of paclitaxel versus
mitomycin in advanced breast cancer. Semin Oncol 22:33-39, 1995
32. Downing R, Windsor CWO Disturbance of sensation after mastectomy. Bh4J
2881650, 1984
33. Edwards EA: Surgical anatomy of the breast. In Goldwyn RM (ed): Plastic and
Reconstructive Surgery of the Breast. Boston, Little, Brown, 1976
34. Eisenach JC, Chuanyao T: Site of hernodynamic effects of intrathecal a,-adrenergic
agonists. Anesthesiology 74:766-771, 1991
35. Farber GA, Burks JW: Chlorprothixene therapy for herpes zoster neuralgia. South
Med J 6780&812, 1974
36. Farina MA, Newby BG, Lani HM: Innervation of the nipple-areola complex. Plast
Reconstr Surg 66497-501, 1980
37. Fields H L Central nervous system mechanisms for control of pain transmission,In
Fields HL (ed): Pain. New York, McGraw-Hill, 1987,pp 99-131
38. Fields HL: Painful dysfunction of the nervous system. In Fields HL (ed): Pain. New
York, McGraw-Hill, 1987,pp 133-169
39. Finnesson BE: Diagnosis and Management of Pain Syndromes. Philadelphia, WB
Saunders, 1962, pp 233-235
40. Flower RJ, Moncada S, Vane JR Analgesic-antipyretics and anti-inflammatoryagents:
Drugs employed in the treatment of gout. In Goodman LS, Gilman A, Rall TW, et al
(eds): The Pharmacologic Basis of Therapeutics, MacMillan Publishing Company.
41. Foley KM: Pain syndromes in patients with cancer. Med Clin North Am 71:177-178,
1978
42. Fowler TJ, Ochoa J: Unmyelinated fibers in normal and compressed peripheral nerves
of the baboon: A quantitative electron microscopic study. Neuropathol Appl Neuro-
biol 1:247-265, 1975
43. Friedman AH, Bullitt E: Dorsal root entry zone lesions in the treatment of pain
99~270-274,1991
1985, pp 674-715

POSTMASTECTOMYAND POSTTHORACOTOMY PAIN 367
following brachial plexus avulsions, spinal cord injury and herpes zoster. Appl
Neurophysiol 51:164-169, 1988
44. Friedman AH, Nashold BS Dorsal root entry zone lesions for the treatment of
postherpetic neuralgia. Neurosurgery 15:969-970, 1984
45. Gaumann DM, Yaksh TL, Tyce GM: Effects of intrathecal morphine, clonidine, and
midazolam on the somato-sympathoadrenal reflex response in halothane-anesthetized
cats. Anesthesiology 73:425-432, 1990
46. Gillette EL, Mahler PA, Powers BE, et al: Late radiation injury to muscle and
peripheral nerves. Int J Radiat Oncol Biol Phy 31:1309-1318, 1995
47. Glassman AH, Perel JM, Shostak M, et al: Clinical implications of imipramine plasma
levels for depressive illness. Arch Gen Psychiatry 34:197-204, 1977
48. Goa KL, Faulds D Vinorelbine: A review of its pharmacological properties and
clinical use in cancer chemotherapy. Drugs Aging 5200-234, 1994
49. Granek I, Ashikari R, Foley KM: The postmastectomy pain syndrome: Clinical and
anatomical correlates. Proceedings of the American Society of Clinical Oncology
3:122, 1984
50. Gunn CC: Prespondylosis and some pain syndromes following denervation supersen-
sitivity. Spine 5:185, 1980
51. Gunn CC: Causalgia and denervation supersensitivity. Am J Acupuncture 7:317, 1979
52. Hallett M, Tandon D, Berardelli A: Treatment of peripheral neuropathies. J Neurol
53. Hansen JL: Intercostal neuralgia following thoraco-abdominal surgery. Acta Chir
54. Hansen JL: Thoracotomi og intercostalneuralgi. Nord Med 461710, 1951
55. Holmes FA, Valero V, Walters RS, et al: The M. D. Anderson Cancer Center experi-
ence with Taxol in metastatic breast cancer. Monogr Nat Cancer Inst 15:161-169, 1993
56. Jamison K, Wellisch DK, Katz RI, et al: Phantom breast syndrome. Arch Surg 114:93-
95, 1979
57. Jensen TS, Rasmussen P: Amputation. In Wall PD, Melzack R (eds):Textbook of Pain.
Edinburgh, Churchill Livingstone, 1984, pp 402412
58. Johnstone PA, DeLuca AM, Bacher JD, et al: Clinical toxicity of peripheral nerve to
intraoperative radiotherapy in a canine model. Int J Radiat Oncol Biol Phy 32:1031-
1034, 1995
59. Kalso E, Perttunen K, Kaasinen S: Pain after thoracic surgery. Acta Anaesthesiol
Scand 3696-100, 1992
60. Karydas I, Fentiman IS, Habib F, et al: Sensory changes after treatment of operable
breast cancer. Breast Cancer Res Treat 8:55-59, 1986
61. Kroner K, Knudsen UB, Lundby L, et al: Long-term phantom breast syndrome after
mastectomy. Clin J Pain 8:346-350, 1992
62. Kroner K, Krebs B, Skov J, et al: Immediate and long-term phantom breast syndrome
after mastectomy: Incidence,clinicalcharacteristics and relationship to premastectomy
breast pain. Pain 36:327-334, 1989
63. Lehman C, Gumener R, Montandon D: Sensibility and cutaneous reinnervation after
breast reconstruction with musculocutaneous flaps. Ann Plast Surg 26:325-327, 1991
64. Lembeck F Sir Thomas Lewis's nocifensor system, histamine and substance-P-con-
taining primary afferent nerves. TINS 6:106-108, 1983
65. Lerut T, Coosemans W, Christiaens R, et al: The Belsey Mark IV antireflux procedure:
Indications and long-term results. Acta Gastroenterol Belg 53:585-590, 1990
66. Lloyd JW, Barnard JDW, Glynn CJ: Cryoanalgesia: A new approach to pain relief.
Lancet 2:932-933,1976
67. Long DM Electrical stimulation of the nervous system for pain control. Elec-
troencephalogr Clin Neurophysiol 34(suppl):343-348, 1978
68. Long DM. Uses of percutaneous electrical stimulation of the nervous system. Med
Prog Techno1 5:47-50, 1977
69. Lotze MT, Duncan MA, Gerber LH, et al: Early versus delayed shoulder motion
following axillary dissection. Ann Surg 193:288-295, 1981
70. Maciewicz R, Bouchoms A, Martin JB: Drug therapy for neuropathic pain. Clin J Pain
1:3949, 1985
Neurosurg Psychiatry 48:1193-1207, 1985
Scand 433(suppl):180-182, 1973

71. Matsunaga M, Dan K, Manabe FY, et al: Residual pain of 90 thoracotomy patients
72. McLachlan EM, Janig W, Devor M, et al: Peripheral nerve injury triggers noradrener-
73. Meglio M, Cioni B, Prezioso A, et al: Spinal cord stimulation in the treatment of
74. Mellick GA, Mellick LB: Gabapentin in the management of reflex sympathetic dystre
75. Mellick LB, Mellick GA: Successful treatment of reflex sympathetic dystrophy with
76. Melzack R: Prolonged relief of pain by brief, intense transcutaneous somatic stimula-
77. Melzack R, Wall PD: Pain mechanisms: A new theory. Science 150:971-978, 1965
78. Montaga W: Histology and cytochemistry of human skin: XXXV. The nipple and
79. Moosman DA. Anatomy of the pectoral nerves and their preservation in modified
80. Murdoch LA: Gabapentin-a novel anticonvulsant. Axone 16:56, 1994
81. Nara T: Histamine and 5-hydroxytryptamine in human scar tissue. Ann Plast Surg
14:244247, 1985
82. Nashold BS, Alexander E Neurosurgical treatment of chronic pain. In Tollison CD
(ed): Handbook of Chronic Pain Management. Baltimore, Williams & Wilkins, 1989,
pp 125-135
83. Nathan PW: Chloroprothixene (Taractan) in post-herpetic neuralgia and other severe
chronic pain. Pain 5:367-371, 1978
84. Nguyen H, Nguyen HV:The 2 key muscles in thoracotomy for excision of the lung:
The latissmus dorsi and the levator scapulae muscles. J Chir 123:626-634, 1986
85. Nielsen OS, Munro AJ,Tannock IF: Bone metastases: Pathophysiology and manage-
ment policy. J Clin Oncol 9:509-524,1991
86. Olsen NK, Pfeiffer P, Mondrup K, et al: Radiation-induced brachial plexus neuropathy
in breast cancer patients. Acta Oncol 29:885-890, 1990
87. Paredes JP, Puente JL, Potel J: Variation in sensitivity after sectioning the inter-
costobrachial nerve. Am J Surg 160:525-528, 1990
88. Parsons JT, Bova FJ, Fitzgerald CR, et al: Radiation optic neuropathy after megavol-
tage external-beam irradiation: Analysis of time-dose factors. Int J Radiat Oncol Biol
89. Powles TJ, Jones AL, Judson IR, et al: A randomised trial comparing combination
chemotherapy using mitomycin C, mitozantrone and methotrexate (3M) with vincris-
tine, anthracycline and cyclophosphamide (VAC) in advanced breast cancer. Br J
Cancer 64:40&410, 1991
90. Puke MJ, Xu XJ, Wiesenfeld-Hallin Z: Intrathecal administration of clonidine sup-
presses autotomy, a behavioral sign of chronic pain in rats after sciatic nerve section.
Neurosci Lett 133:199-202, 1991
91. Raja SN, Treede RD, Davis KD, et al: Systemic alpha-adrenergic blockade with
phentolamine: A diagnostic test for sympathetically maintained pain. Anesthesiology
92. Ramamurthy S, Hickey R, Maytorena A, et al: Long thoracic nerve block. Anesth
93. Rauck RL, Eisenach JC, Jackson K, et al: Epidural clonidine treatment for refractory
94. Roberts WA, Elardo SM: Sympathetic activation of A-delta nociceptors. Somatosens
95. Rowlingson JC, DiFazio CA, Foster J, et a1 Lidocaine as an analgesic for experimental
96. Sanchez-Ledesma MJ, Garcia-March G, Diaz-Cascajo P, et al: Spinal cord stimulation
97. Sanjue H, J m 2 Sympathetic facilitation of sustained discharge of polymodal nmi-
with malignancy and non-malignancy. Pain 5(suppl):S148,1990
gic sprouting within the dorsal root ganglia. Nature 363:543-546, 1993
postherpetic pain. Acta Neurochir 46(suppl):6546, 1989
phy [letter].J Pain Symptom Manage 10:265-266, 1995
gabapentin [letter]. Am J Emerg Med 13:96, 1995
tion. Pain 1:357-373, 1975
areola. Br J Dermatol 83:2-13, 1970
radical mastectomy. Am J Surg 139:883, 1980
Phys 30:755-763, 1994
74:691-698, 1991
Analg 71:197-199, 1990
reflex sympathetic dystrophy. Anesthesiology 79:1163-1169, 1993
Res 3:3344, 1985
pain. Anesthesiology 52:20-22, 1980
in deafferentation pain. Stereotact Funct Neurosurg 53:4045, 1989
ceptors. Pain 38:85-90, 1989

POSTMASTECTOMY AND POSTTHORACOTOMY PAIN 369
98. Scher HI, Yagoda A: Bone metastases: Pathogenesis, treatment, and rationale for use
99. Simmel ML: A study of phantoms after amputation of the breast. Neuropsykologica
of resorption inhibitors. Am J Med 82:6-28, 1987
4:331-350, 1966
100. Simons DG: Muscle pain syndromes, part I. Am J Phys Med 54289,1975
101. Simons DG: Muscle pain syndromes, part 11. Am J Phys Med 55:15, 1976
102. Shealy CN, Taslitz N, Mortimer J, et al: Electrical inhibition of pain: Experimental
evaluation. Anesth Analg 46299-305, 1967
103. Somlo G, Doroshow JH, Forman SJ, et al: High-dose cisplatin, etoposide, and cyclo-
phosphamide with autologous stem cell reinfusion in patients with responsive meta-
static or high-risk primary breast cancer. Cancer 73:125-134, 1994
104. Southwick HW, Slaughter DP, Humphrey LT Anatomy and physiology of the breast
and axilla. In Southwick (ed): Surgery of the Breast. Chicago, Year Book Medical
Publishers, 1968, pp 15-21
105. Stevens PE, Dibble SL, Miaskowski C: Prevalence, characteristics, and impact of
postmastectomy pain syndrome: An investigation of women's experiences. Pain
106. Stracke H, Meyer UE, Schumacher HE, et al: Mexiletine in the treatment of diabetic
neuropathy. Diabetes Care 15:1550-1555, 1992
107. Swerdlow M, Cundill JG: Anticonvulsant drugs used in the treatment of lancinating
pain: A comparison. Anaesthesia 361129-1132, 1981
108. Tanelian DL, Brose WG: Neuropathic pain can be relieved by drugs that are use-
dependent sodium channel blockers: Lidocaine,carbamazepine, and mexiletine. Anes-
thesiology 74:949-951, 1991
109. Tanelian DL, MacIver MB: Analgesic concentrations of lidocaine suppress tonic A-
delta and C fiber discharges produced by acute injury. Anesthesiology 74:934-936,
1991
110. Taylor CP: Gabapentin: Mechanism of action. In Levy RH, Mattson RH, Meldrum BS
(eds): Antiepileptic Drugs. New York, Raven Press, 1995,pp 829-841
111. Temple WJ, Ketcham AS Preservation of the intercostobrachial nerve during axillary
dissection for breast cancer. Am J Surg 150:585-588, 1985
112. Terzis JK, Vincent MI', Wilkins LM, et al: Breast sensibility: A neurophysiological
appraisal in the normal breast. AM Plast Surg 19:318-322, 1987
113. Tower SS The reaction of muscle to denervation. Physiol Rev 19:1, 1939
114. Travel1JG, Simons DG: Myofascial Pain and Dysfunction: The Trigger Point Manual.
Baltimore, Williams & Wilkins, 1983
115. Vecht CJ,Van de Brand HJ, Wajer OJM:Post-axillary dissection pain in breast cancer
due to a lesion of the intercostobrachial nerve. Pain 38:171-176, 1989
116. Vujaskovic Z , Gillette SM, Powers BE, et a1 Ultrastructural morphometric analysis of
peripheral nerves after intraoperative irradiation. Int J Radiat Biol 6871-76, 1995
117. Wallace MS, Wallace AM, Lee J, et al: Pain after breast surgery: A survey of 282
women. Pain 66:195-205, 1996
118. Watson CP, Evans RJ, Reed K, et al: Amitriptyline versus placebo in postherpetic
neuralgia. Neurology 32:671-673, 1982
119. Watson CPN, Evans RJ, Watt VR The post-mastectomy pain syndrome and the effect
of topical capsaicin. Pain 38:177-186, 1989
120. Watson CPN, Evans RJ: A comparative trial of amitriptyline and zimelidine in
postherpetic neuralgia. Pain 23:387-394, 1985
121. Watson CPN, Evans RJ:Intractable pain with breast cancer. Can Med Assoc J 126:263-
266, 1982
122. Weinstein S, Vetter RJ, Sersen EA: Phantoms following breast amputation. Neuropsy-
kologica 8:185-197, 1970
123. Willis WD Modulation of primate spinothalamic tract discharges. In Kruger L,
Liebeskind JC (eds): Advances in Pain Research and Therapy. New York, Raven
Press, 1984, pp 217-240
124. Woolf CJ, Wiesenfeld-Hallin Z: The systemic administration of local anaesthetics
produces a selective depression of C-afferent fibre evoked activity in the spinal cord.
Pain 23:361-374, 1985
61161-68, 1995

125. Yaksh TL: New horizons in our understanding of the spinal physiology and pharma-
cology of pain processing. Semin Oncol 20(suppl 1):6-18, 1993
126. Yaksh TL, Al-Rodham NRF, Jensen TS: Sites of action of opiates in production of
analgesia. Prog Brain Res 77:371-394, 1988
127. Yaksh TL, Pogrel JW,Lee YW, et al: Reversal of nerve ligation-induced allodyniaby
spinal alpha-2 adrenoceptor agonists. J Pharmacol Exp Ther 272:207-214, 1995
128. Yehuda S, Youdim MB: The increased opiate action of beta-endorphin in iron-
deficient rats: The possible involvement of dopamine. Eur J Pharmacol 104:245-251,
1984
129. Zimmerman M: Peripheral and central nervous mechanisms of nociception, pain and
pain therapy: Facts and hypotheses. In Bonica JJ, Liebeskind JC, Albe-Fessard DG
(eds):Advances in Pain Research and Therapy. New York, Raven Press, 1979,pp 3-32
Address reprint requests to
Anne M. Wallace,MD
Department of General and Plastic Surgery
University of California, San Diego
9500 Gilman Drive
La Jolla, CA 92093-8890

Understanding postmastectomy and postthoracotomy pain mechanisms

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Similar to Understanding postmastectomy and postthoracotomy pain mechanisms

Similar to Understanding postmastectomy and postthoracotomy pain mechanisms (20)

More from Jason Attaman

More from Jason Attaman (20)

Recently uploaded

Recently uploaded (20)

Understanding postmastectomy and postthoracotomy pain mechanisms