++
Despite its prevalence, our understanding of chronic postoperative pain
and the potential means of risk reduction are somewhat deficient. We need to
classify these chronic pain syndromes according to symptoms and mechanisms
and greater emphasis needs to be placed on preventing its development.
Preemptive analgesic techniques may play a role in reducing the incidence of
certain chronic postsurgical pain syndromes,82 and future
large-scale randomized controlled trials are necessary to support these
initial findings. Four chronic pain syndromes that are important clinically
to the anesthesiologist are complex regional pain syndrome, phantom limb
pain, chronic donor site pain, and postthoracotomy pain syndrome.
+++
Complex Regional Pain Syndrome
++
Complex regional pain syndrome (CRPS) is a disorder characterized by
the presence, following a noxious event, of regional pain and sensory
changes such as temperature alterations, abnormal skin color, abnormal
sudomotor activity, or edema.83 Its onset is associated
with a history of trauma (that is often innocuous) or immobilization, and
there is typically no correlation between the severity of the initial injury
and the ensuing painful syndrome.84 The Consensus
Conference of the International Association for the Study of Pain (IASP) has
identified two forms of CRPS: CRPS type I (formerly known as reflex
sympathetic dystrophy) and CRPS type II (formerly known as
causalgia).85 The characteristics of each are summarized
in Table 76–2.
++
++
Because there has been some debate regarding nomenclature and diagnostic
standards, the IASP has also recently suggested a formal set of criteria for
the diagnosis of CRPS.86,87 Accordingly, patients should
have:
++
At least one symptom in each of the following categories:
And at least one sign within two or more of the following categories:
++
CRPS is often, but not always, associated with a state of
sympathetically maintained pain (SMP).88 This type of pain
is sustained by sympathetic efferent innervation or by circulating
catecholamines and is relieved by specific sympatholytic procedures such as
nerve blocks. Sympathetically independent pain (SIP), in contrast, does not
respond to sympatholytic blocks. Patients with CRPS may have varying
elements of SMP or SIP throughout the course of the
disease.89
++
CRPS is a potentially debilitating syndrome that leaves many patients
without use of the affected limb. Once diagnosed, treatment should begin
immediately. A multifocal approach is often recommended, including a
combination of physiotherapy, antidepressant and anticonvulsant medications,
steroids, sympathetic blocks, and, in some cases, spinal cord
stimulation.89
++
The incidence of CRPS occurring after surgery varies and may be
underreported.90 Approximately 20% of CRPS patients who
present to chronic pain clinics have a history of prior surgical procedures
in the affected area.91,92 There are accounts of CRPS
after such procedures as breast surgery,93,94 radial
artery harvesting for cardiac surgery,95 skin nevus
excision,96 and lumbar spine surgery.97
However, perhaps not surprisingly, most reports of postoperative CRPS occur
in the orthopedic population, especially after operations on the
extremities. Estimates for various procedures include 2.3% following knee
arthroscopy,98 2.1–5% following carpal tunnel
release,99–101 and 0.8–13% following total knee
arthroplasty.102–105 There is a wide range of reported
incidences of this disorder after surgery, and this may be due to
differences in methodology, particularly with respect to the interval at
which the patients are assessed.106 For example, patients
assessed 3 months postoperatively are likely to have a different clinical
presentation than those assessed 1 year out. Also, many of the reports
originated before the definition of the syndrome was modified in the
mid-1990s, so the external validity may be compromised for earlier
investigations. Patients with CRPS who undergo surgery on the affected limb
are thought to be at increased risk for recurrence or worsening of
symptoms.107,108
++
People who suffer the loss of a limb, either traumatically or
surgically, almost always report some degree of perceived sensation in the
lost limb. This phenomenon, first described over 400 years ago, was dubbed
“phantom limb” in 1871 by S.W. Mitchell.109 A distinction
should be made between phantom limb pain (painful sensations referred to the
absent limb), phantom limb sensation (any sensation in the absent limb,
except pain), and stump pain (pain localized in the stump), although each of
these may coexist in an individual patient at different
times.110
++
Early studies reported that the incidence of phantom pain in amputees
was below 5%.111 Recent literature, however, suggests
that the incidence is much higher and is probably between 50% and
80%.112–114 The discrepancy may be explained by
differences in methodologies. Early studies tended to base prevalence on the
patient's request for pain relief, which may have underestimated the problem
in patients who were reluctant to report pain to medical staff. Several risk
factors have been identified for the development of phantom limb pain
including the degree of preoperative pain, the magnitude of intraoperative
noxious input, the intensity of postoperative pain, and psychological
factors.115,116
++
Typically, phantom pain occurs early in the postamputation course with up to
70% of patients experiencing pain in the first several days after the
injury.117,118 Although phantom pain can be constant in
some cases, it is predominantly intermittent in nature.112
Some patients report a background low-intensity pain coupled with
intermittent episodes of excruciating, debilitating
pain.119 It is often characterized as knife-like or
stabbing, but sufferers frequently describe other varied sensations, such as
shooting, squeezing, burning, aching, and
throbbing.119,120 Pain can be perceived anywhere along the
absent limb, but is typically reported in distal areas (ie, hands and feet)
as opposed to more proximal locations.121 In prospective
studies of the duration of phantom pain, patients tend to report an overall
decrease in pain intensity and frequency of attacks over time, with some
patients experiencing a complete remission. Unfortunately, this is the
exception, and up to 60% of amputees are left with some degree of phantom
pain 12–24 months after loss of the affected
limb.112,116,118
++
The mechanisms of phantom pain are not completely clear. As is the case with
other types of neuropathic pain, there are likely both peripheral and
central nervous system factors at play. Increased spontaneous activity of
both afferent peripheral nerves and dorsal root ganglion cells has been
observed experimentally following the transection of a nerve. In addition,
the sympathetic nervous system may have a role in sensitizing and
maintaining the abnormal afferent output from damaged nerve fibers after
amputation. It is now known that the CNS, including spinal cord, brainstem,
thalamus, and cerebral cortex, undergoes significant functional
reorganization following amputation. Studies using functional brain imaging
have shown that areas of the somatosensory cortex corresponding to the
amputated structure become responsive to neighboring cell assemblies as
early as 10 days after the injury.122 For example, a
common finding in upper extremity amputees is a shift of the cortical
representation of the mouth into the (deafferented) hand
area.123 The degree to which this reorganization occurs
has been correlated with the magnitude of phantom limb pain, underscoring
the role that CNS plasticity has in the generation and maintenance of
neuropathic pain.124
++
The treatment of phantom limb pain remains challenging, despite the
multitude of proposed treatments. A review of therapies for phantom pain
published in 1980 reported over 40 different methods, but concluded that few
provided consistent relief.125 The majority of
interventions are medical and consist of the same drugs used for the
management of other neuropathic pain conditions, such as tricyclic
antidepressants and anticonvulsants.110 Other modalities
include nonmedical options such as transcutaneous electrical nerve
stimulation (TENS), massage, and acupuncture. Surgical therapies such as
neurectomy, rhizotomy, and cordotomy are probably the least effective and
may be best reserved for the most intractable cases.
++
Several investigations have focused on utilizing preventative regional
analgesic techniques to reduce perioperative pain and long-term phantom pain
following lower extremity amputation surgery.126 Bach and
colleagues59 initially examined the effect of epidural
morphine, epidural bupivacaine, or both in combination for 3 days before
amputation (n = 11) or conventional analgesia (n = 14). All patients received
epidural or spinal anesthesia for amputation and received conventional
analgesics postoperatively. The incidence of phantom pain was reduced 6
months after amputation but not after 1 week or after 12 months in the
epidural treatment group compared with the control group. Jahangiri and
coworkers60 confirmed the beneficial effects of
perioperative epidural administration on preventing phantom pain following
amputation surgery. These investigators examined the effect of an epidural
infusion of bupivacaine, diamorphine, and clonidine (n = 13) preoperatively
and maintained for at least 3 days postoperatively. For comparison, the
control group (n = 11) received on-demand opioid analgesia. These authors
observed a significant reduction in the incidence of phantom pain at 1 year
following surgery. However, the largest prospective study
(n = 60) to examine the effect of epidural analgesia on phantom pain failed
to document any benefit at 7 days, 3 months, 6 months, and 12 months
postoperatively. Similarly, clinical investigations evaluating the efficacy
of continuous postoperative regional analgesia by nerve sheath block for
amputation surgery have been equivocal, with some studies revealing
beneficial effects,54,127 and others demonstrating no
long-term benefit.53,55 It is interesting that perineural
analgesia provided for a reduction in phantom pain in these two
studies54,127 since this technique is ineffective in
blocking nociceptive inputs from the pre- or intraoperative periods. A later
study investigated whether postamputation stump and phantom pain could be
reduced by preoperative epidural block with bupivacaine and diamorphine
compared with intraoperative placement of a perineural catheter infusing
bupivacaine.62 These investigators observed that both
regional techniques were equally effective in preventing phantom pain, but
the epidural analgesic technique was more effective in relieving stump pain
in the immediate postoperative period.
++
Unfortunately, many of the regional analgesic studies evaluating the effect
on reducing long-term phantom pain have significant design flaws, including
that they were not prospective, randomized, or blinded; they utilized either
no control group or historical controls; they investigated a heterogeneous
study group; or they lacked sufficient power. The authors of a recent
systematic review of the literature concluded that because of the poor
quality and contradictory results, the randomized and controlled trials do
not provide evidence to support any particular treatment of phantom limb
pain in the acute perioperative period or later.126
++
In fact, a number of reports of peripheral nerve block and neuraxial
techniques appear to have caused an exacerbation of phantom pain. These are seen
primarily with lower limb amputations, although the phenomenon has been
described following brachial plexus block for revision of an arm
amputation.128 This “reactivated” phantom pain associated
with neural blockade is often severe and unresponsive to parenteral opioids.
However, agents that are usually effective against neuropathic pain, such as
lidocaine and carbemazepine, have been used
effectively.129 The mechanism by which regional anesthesia
provokes this painful response is not completely understood. One possibility
is that an absence of afferent sensory input after spinal anesthesia may
decrease the level of inhibition and increase self-sustained neural activity
that is common in the spinal cord following
deafferentation.130 Since a subanesthetic dose of
thiopental (1 mg/kg) is effective at terminating the reactivation phantom
pain, a central mechanism is implied.131 Although some
authors suggest avoiding spinal anesthesia in patients with a history of
lower limb amputation,132 the benefits of regional
anesthesia must be weighed against the potential for this unusual and
bizarre event to occur.
+++
Chronic Donor Site Pain
++
The occurrence of chronic pain following spinal fusion surgery is not
an uncommon complication. Autogenous bone grafts from the ilium are
frequently harvested for the purposes of bone fusion in patients undergoing
spinal stabilization surgery. Often, the pain from the donor site is more
severe than that from the laminectomy incision.133–136
Although this pain usually resolves over a period of several weeks, it may
persist and represent a significant source of postoperative
morbidity.133–136 In fact, donor site pain has been
reported in up to 39% of patients at 3 months, 38% at 6 months, 37%
at 1 year, and 19% at 2 years after bone graft harvesting from the iliac
crest.135–137
++
The precise mechanism of donor site pain remains obscure. It has been
postulated to be muscular or periosteal in nature secondary to stripping of
the abductors from the ilium.133 In addition, the pain may
be neuropathic in origin secondary to injury to small sensory nerves at the
donor site. One nerve frequently injured while harvesting bone graft from
the anterior ilium is the lateral femoral cutaneous nerve, which has been
reported in up to 10% of cases.134 Injury to the
ilioinguinal nerve has also been reported, especially when the bone graft is
harvested from the anterior ilium.134 The superior cluneal
nerves pierce the lumbodorsal fascia and cross the posterior iliac crest 8
cm lateral to the posterior superior iliac spine.138
Injury to these nerves may occur while harvesting bone graft from the
posterior ilium and may result in transient or permanent numbness and pain
over the buttock area.
++
Two recent studies have demonstrated a significant reduction in the
incidence of chronic donor site pain with the preemptive administration of
analgesics.77,137 Houghton and
associates139 have shown that the local application of a
low dose of morphine can effectively block the development of hyperalgesia
and allodynia in a rat model of bone damage. This analgesic effect was
considered to be mediated through μ-opioid receptor action in the
bone. Reuben and colleagues137 subsequently evaluated the
analgesic effect of low-dose morphine administered to the site of bone graft
harvesting in patients undergoing spinal fusion surgery. Sixty patients were
randomized to receive either saline infiltration into the harvest site
(n = 20), intramuscular morphine 5 mg (n = 20), or morphine 5 mg infiltrated
into the harvest site (n = 20). This study revealed that morphine infiltrated
into the bone graft harvest site resulted in a significant reduction in pain
scores and opioid use for the first 24 h following surgery. Furthermore, the
association of chronic donor site pain was significantly lower in the local
morphine group (5%) than in the intramuscular morphine (37%) or saline
infiltration (33%) groups. Another study from the same institution
examined the analgesic effect of preemptive COX-2 administration for spinal
fusion surgery.77 It has been shown that COX-2 plays an
integral role in the processes of peripheral and central
sensitization,140 and it is possible that early and
sustained treatment with COX-2 inhibitors may thwart the progression of
acute to chronic pain.141 Eighty patients scheduled to
undergo instrumented posterior spinal fusion were randomized to receive
either celecoxib 400 mg 1 h prior to surgery and then 200 mg every 12 h
postoperatively for the first 5 days or matching placebo at similar time
intervals. Patients administered celecoxib reported lower pain scores and
had less opioid use during the first 5 postoperative days. Chronic donor
site pain was significantly higher in the placebo group (12/40, 30%) than
in the celecoxib group (4/40, 10%) at 1 year following
surgery.77 The development of neuropathic pain following
spinal fusion surgery may in part be mediated by central COX-2 expression
resulting in central neuronal plasticity. Spinal COX-2 has been implicated
in the development of allodynia after nerve injury in
rats,142 and peripheral prostaglandins have been
implicated in the pathogenesis of neuropathic pain.143
However, after the development of neurogenic inflammation, the responses to
mechanical stimuli are not affected by spinal COX-2
inhibition.142 Thus, spinal prostaglandin synthesis may be
important for the induction and initial expression, but not for the
maintenance of spinal cord hyperexcitability.70 This may
explain the lack of analgesic efficacy of NSAIDs for treatment of chronic
donor site pain observed in the study by Reuben and colleagues.
++
These studies77,137 highlight the importance of utilizing
preemptive analgesics for pain management following spinal fusion surgery.
It has been suggested that effective treatment of acute pain, particularly
when accompanied by a neuropathic element, prevents the development of
chronic postsurgical pain syndromes.25,144–146 The
reduction in chronic donor site pain may be attributed to a preemptive or
preventative analgesic effect in which a reduction in spinal cord
neuroplasticity derives from prompt reduction in the perioperative noxious
afferent input associated with surgery. An early reduction in acute pain may
facilitate early postoperative ambulation147 and decrease
fear-avoidance behaviors148,149 also contributing to a
reduction in chronic postsurgical pain. Further studies are needed to assess
the efficacy of preemptive analgesic techniques on reducing chronic donor
site pain.
+++
Postthoracotomy Pain Syndrome
++
Pain following thoracic surgery has been reported to be among the most
intense clinical experiences known.150 The nociceptive
pathways responsible for postthoracotomy pain are still poorly
understood.151 Possible sources of nociceptive input that
may contribute to postoperative pain following thoracic surgery are multiple
and include the site of the surgical incision; disruption of the intercostal
nerves; inflammation of the chest wall structures adjacent to the incision,
pulmonary parenchyma, or pleura; and thoracostomy drainage
tubes.152 Unrelieved acute pain following thoracic surgery
may contribute not only to postoperative pulmonary
dysfunction,153 but also to the development of
postthoracotomy pain syndrome.25,144–146
++
Postthoracotomy pain syndrome is defined as pain that recurs or persists
along a thoracotomy incision for at least 2 months following the surgical
procedure.154 The true incidence of postthoracotomy pain
syndrome is difficult to determine, with a reported range from 5% to
80%.155 Different definitions used to describe and
assess pain, lack of large, prospective studies, small sample size, varying
surgical techniques, varying perioperative management, and different periods
of follow-up care have all contributed to the difficulty in determining the
true incidence of this postsurgical pain syndrome.155
Nonetheless, it has been estimated that half of all patients still alive
1–2 years after thoracotomy will suffer with persistent chest wall
pain.156 Furthermore, as much as 30% of patients might
still experience pain 4–5 years after surgery.156
++
The exact mechanism for the pathogenesis of postthoracotomy pain syndrome is
still unclear. Similar to chronic donor site pain, it has been suggested
that both neuropathic and myofascial nociceptive pathways contribute to the
development of postthoracotomy pain syndrome. Although damage to cutaneous
or deep (muscle, joint, and viscera) tissue is typically associated with
peripheral inflammation, damage to neural structures often leads to
pathologic pain.10 Damage to intercostal nerves during
thoracic surgery leads to neural degeneration, neuroma formation, and the
generation of spontaneous neural inputs.10 Evidence
suggests that although nociceptive and neuropathic pain depend on separate
peripheral mechanisms, they are both significantly influenced by changes in
CNS function.10 The resultant neuroplastic changes in the
CNS have the capacity to contribute to persistent pathologic pain following
surgery.10
++
A variety of preemptive or preventative analgesic techniques have been
utilized in an attempt to reduce sustained nociceptive input into the CNS
and concomitant acute and chronic pain following thoracic surgery. In a
retrospective review of 1000 thoracic surgery patients, Richardson and
colleagues157 assessed the efficacy of acute postoperative
pain on the incidence of postthoracotomy pain syndrome at 2 months following
surgery. The use of systemic opioids alone was associated with a 23.4%
incidence of postthoracotomy pain syndrome.157
Interestingly, the use of intraoperative intercostal neurolysis with a
cryoprobe increased the incidence of chronic pain to
31.6%.157 In contrast, the use of continuous
paravertebral infusion of bupivacaine in conjunction with systemic opioids
decreased the incidence to 14.8%.157 Furthermore, the
addition of an NSAID to this analgesic regimen reduced the incidence of
postthoracotomy pain syndrome to 9.9%.157 These
findings highlight the importance of utilizing a multimodal analgesic
regimen for the prevention of acute and chronic postsurgical pain. In
addition, even when a perioperative local anesthetic block is utilized,
nociceptive afferent pathways to the CNS can still be activated leading to
central sensitization.157 There appears to be two forms of
nociceptive input from peripheral inflamed tissue to the
CNS.140 The first is mediated by neural activity
innervating the area of injury which may be reduced with local anesthetic
neural blockade or peripherally acting COX-2 inhibitors. The second pathway
is humorally mediated, in which interleukins reach the CNS via systemic
pathways, resulting in upregulation of COX-2 in the CNS. This latter pathway
is not affected by regional anesthesia and only blocked by centrally acting
COX-2 inhibitors.140 Thus it has been demonstrated that
the addition of a centrally acting COX-2 inhibitor to a local anesthetic
block can result in a significant decrease in CNS prostaglandin E2 (PGE2)
levels and improved postoperative analgesia.158 McCrory
and coworkers159 confirmed the analgesic benefit of adding
a centrally acting COX-2 inhibitor with neuraxial analgesia for
postthoracotomy pain. This randomized, prospective, double-blind study
evaluated the analgesic efficacy of ibuprofen (peripherally acting NSAID),
nimesulide (centrally acting NSAID), or placebo in conjunction with
neuraxial analgesics. This study revealed a significant reduction in
postoperative pain and opioid use with the centrally acting NSAID,
nimesulide, compared with either ibuprofen or placebo. This pain reduction
correlated with a significant reduction in PGE2 levels in the cerebrospinal
fluid observed in the nimesulide group, which was not seen with either
placebo or ibuprofen.
++
In a retrospective study of 159 patients undergoing posterolateral
thoracotomy, Hu and associates160 examined the effects of
thoracic epidural analgesia on the incidence of postthoracotomy pain
syndrome. Thoracic epidural anesthesia was given to 119 patients in
conjunction with general anesthesia, and 40 patients received only general
anesthesia. Thoracic epidural analgesia was initiated prior to surgical
incision and maintained intraoperatively with an infusion of bupivacaine
0.5%. Following surgery, these patients were administered epidural
morphine every 12 h for the first 3 days. These authors reported a similar
incidence in postthoracotomy pain syndrome in the epidural analgesia group
(42%) compared with the general anesthesia group (39%). In contrast to
these findings, Obata and colleagues,161 in a prospective,
randomized, double-blind study, revealed a significant analgesic benefit
when epidural analgesia was initiated prior to thoracic surgery. These
investigators compared the analgesic effects of a continuous thoracic
epidural infusion of mepivacaine initiated 20 min prior to surgery with one
begun at the completion of surgery and continued for the first 3
postoperative days. This study revealed a significant reduction in both
acute and chronic postthoracotomy pain at 6 months following surgery in the
preincisional compared with the postincisional epidural analgesia group. The
beneficial effects of epidural analgesia following thoracic surgery were
confirmed in a more recent prospective, randomized, double-blind study
performed by Senturk and coworkers.162 These investigators
compared the analgesic effects of three different analgesic techniques: (1)
thoracic epidural analgesia initiated before, or (2) after surgical
incision, and (3) intravenous patient controlled analgesia (PCA) on acute
postoperative pain and the incidence of postthoracotomy pain syndrome 6
months following surgery. Patients in the prethoracic epidural group
reported significantly less pain than those receiving the postthoracic
epidural or the PCA groups for the first 48 h following surgery. The
incidence of postthoracotomy pain syndrome was also significantly lower in
the prethoracic epidural group (45%) than for those who received either
the postthoracic epidural (63%) or the PCA (78%). Although both Obata
and colleagues161 and Senturk and
coworkers162 demonstrated a beneficial effect with the
preemptive administration of epidural analgesia for thoracic surgery,
Ochroch and associates163 were unable to report similar
findings. In a prospective, randomized, double-blind study of 157 patients,
these investigators examined the analgesic efficacy of thoracic epidural
analgesia initiated prior to surgical incision or at the time of rib
approximation. Overall, there were no differences in pain scores or activity
level during hospitalization or after discharge between the two groups.
Furthermore, the number of patients reporting pain 1 year following surgery
was similar for the two groups.
++
From these studies, it can be concluded that the method of perioperative
pain management has a variable effect on the incidence of postthoracotomy
pain syndrome. The reason for this variability may be explained by the
multiple sources of nociceptive afferent pathways involved in the perception
of pain following thoracic surgery.152 These pain sources
may be conveyed to the CNS via somatic nerves (intercostal nerves), phrenic
nerve, cranial nerve (vagus nerve), the sympathetic nervous system, the
parasympathetic system, and the brachial plexus.155 It has
been demonstrated that thoracic epidural analgesia is unable to abolish
somatosensory evoked potential resulting from thoracic dermatomal
stimulation, suggesting that this regional technique may be insufficient for
blocking all nociceptive pain pathways.164,165 Therefore,
the use of regional blockade by itself is insufficient in providing complete
pain relief and preventing central sensitization of the nervous system
following thoracic surgery. A multimodal analgesic regimen, in which
regional blocks are combined with NSAIDs and other analgesics, as described
by Richardson and colleagues,157 may provide for a
reduction in both acute and chronic pain following thoracic surgery. Future
prospective, randomized studies are needed to evaluate the efficacy of
utilizing preventative multimodal analgesic techniques on the incidence of
postthoracotomy pain syndrome.