MEDICAL INTELLIGENCE

Gabapentin in Pain Management

Jianren Mao,

MD, PhD,

and Lucy L. Chen,

MD

MGH Pain Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

abapentin [1-(aminomethyl)cyclohexane acetic

acid] is a structural analog of -aminobutyric
acid (GABA), which was initially introduced in
1994 as an antiepileptic drug (AED), particularly for
partial seizures. For a long time, AEDs such as carbamazepine have been recognized as adjunctive drugs
for treating certain symptoms of chronic pain syndromes. It is then not surprising that gabapentin was
soon found to be promising in treating neuropathic
pain associated with postherpetic neuralgia (PHN)
(1,2), postpoliomyelitis neuropathy (3), and reflex
sympathetic dystrophy (4). Placebo-controlled clinical
trials also have indicated a role of gabapentin in treating pain related to diabetic neuropathy (DNP) (5) and
PHN (6).
A number of animal studies have investigated the
effect of gabapentin on signs of neuropathic pain, such
as hyperalgesia and allodynia. Data derived from
these studies are generally in agreement with clinical
observations. More recently, studies on animal models
of acute pain have indicated a role of gabapentin in
ameliorating pain from incisional injury and arthritis
(7,8), implicating even broader use of gabapentin in
treating a variety of pain states. Indeed, it is a common
experience that gabapentin has been increasingly prescribed by pain specialists, neurologists, primary care
physicians, and other physicians for cases in which
pain of nonnociceptive origin is suspected. The clinical
impression that there are fewer side effects of gabapentin often becomes part of the rationale for initiating
gabapentin therapy. However, both the efficacy and
indications of gabapentin for pain treatment are yet to
be established, and there is a lack of consensus with
regard to the dosage, indications for use of gabapentin, and clinical outcome data.
In this article, three lines of evidence will be examined regarding the role of gabapentin in pain treatment: 1) clinical evidence (case reports and trials) for a

This work was supported, in part, by the US Public Health Service

Grant DA08835 (to JM).
Accepted for publication May 15, 2000.
Address correspondence and reprint requests to Jianren Mao,
MD, PhD, MGH Pain Center, Massachusetts General Hospital, Harvard Medical School, 15 Parkman St., Suite WACC-324, Boston, MA
02114. Address e-mail to JMAO@Partners.org.

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role of gabapentin in pain treatment will be discussed

with an attempt to identify pain symptoms that are
likely to be responsive to gabapentin; 2) animal studies of gabapentin on neuropathic pain and other pain
behaviors will be evaluated; and 3) possible mechanisms of gabapentin actions will be considered in relation to mechanisms of neuropathic pain in particular. Finally, clinical issues of gabapentin treatment will
be discussed in the context of its role in neuropathic
pain relief.

Clinical Data
Thus far, information pertaining to the effectiveness of
gabapentin in pain relief is mainly derived from anecdotal case reports. Several open-label, nonplacebocontrolled clinical studies have been conducted. Two
randomized, placebo-controlled clinical trials investigated the effect of gabapentin on pain from DNP and
PHN.

Postherpetic Neuralgia
Gabapentin (900 mg/daily) was first reported to be
beneficial in a 77-year-old female patient with burning
pain in the right T4 dermatome three months after
acute herpes zoster infection (1). Similar results of
decreased PHN pain with gabapentin were shown in
several case reports (2,9), including a retrospective
case review (10). In 1998, a randomized, controlled
clinical trial investigated the effect of gabapentin on
PHN pain (6). In this clinical trial, patients with PHN
pain were randomized into gabapentin (n 113) and
placebo (n 116) groups. During the eight-week trial
period, patients in the gabapentin group (a maximum
daily dose of 3600 mg) reported a reduction of the
daily pain score (0 10 scale) from 6.3 to 4.2 as compared with a half point reduction (from 6.5 to 6.0) in
the placebo group. In addition, patients treated with
gabapentin also showed some improvement in sleep,
affective measures of pain, and quality-of-life outcome
measures (6). However, it is not clear whether the
improvement in sleep and quality of life is related to
the direct effects of medication or secondary to the
reduction of pain.
2000 by the International Anesthesia Research Society
0003-2999/00

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One caveat concerning this clinical trial is that tricyclic antidepressants (TCAs) and/or opioids were
not discontinued in those patients who were receiving
a stable dose range of these co-medications before
beginning gabapentin treatment (6). Because both opioids and TCAs are effective in reducing PHN pain
(11,12), this design makes it difficult to determine the
effect of gabapentin alone on PHN pain. Particularly,
the study did not provide information about how
many patients in the trial received both gabapentin
and co-medications. Thus, the data do not necessarily
establish a causal relationship between gabapentin
and PHN pain reduction, although the trial indicates a
favorable outcome in PHN patients treated with gabapentin. Gabapentin could have its effect on PHN pain
via interacting with the effect of TCAs and/or opioids,
because gabapentin enhances the antinociceptive effects of spinal morphine in the rat tail-flick test (13).
Nonetheless, this study suggests that gabapentin is
likely to be helpful in reducing PHN pain symptoms.

Diabetic Neuropathy
Pain associated with DNP was responsive to gabapentin
in both case reports (2,14,15) and controlled clinical trials
(5,16). In a multi-center randomized (gabapentin 84 subjects; placebo 81 subjects), placebo-controlled trial,
monotherapy with gabapentin (a maximum dose of
3600 mg/day), except for the addition of acetaminophen, aspirin, or serotonin reuptake inhibitors as
indicated, was shown to reduce DNP pain from 6.4 to 3.9
(0 10 scale), as compared with 6.5 to 5.1 in the placebo
control group (5). The data also showed a favorable
outcome of gabapentin in improving sleep disturbance
and quality of life in patients with DNP pain. It should
be noted that global pain scores were used in both DNP
and PHN trials (5,6), and no information was generated
regarding the effect of gabapentin on individual pain
symptoms such as allodynia (nociceptive responses to
innocuous stimulation) and hyperalgesia (exaggerated
nociceptive response to noxious stimulation).

Multiple Sclerosis (MS)

Several case reports have shown a reduction of pain
associated with MS (1720). In two open-label,
nonplacebo-controlled clinical studies (18,20), gabapentin (up to 1200 mg/day) was found to be helpful in
reducing several types of pain in MS patients. Such
pain conditions include painful tonic spasms and dysesthetic or paresthetic symptoms. In general, gabapentin treatment appears to be more effective in reducing paroxysmal pain with throbbing, pricking, and
cramping quality than dull aching pain in MS patients.
These findings suggest that a large-scale, controlled
clinical trial may be warranted to determine the effectiveness of gabapentin in improving pain in MS
patients.

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Neuropathic Cancer Pain

In an uncontrolled clinical study (21), gabapentin was
added to the opioid treatment regimen in 22 cancer
patients whose pain was only partially responsive to
opioid treatment. It was found that pain decreased
from 6.4 to 3.2 (0 10 scale) at one to two weeks after
the addition of gabapentin. In particular, burning pain
was decreased from 5.1 to 2.0 and daily episodes of
shooting pain from 7.2 to 2.2. Allodynia also disappeared in seven of nine patients after the addition of
gabapentin into the treatment regimen. Although a
number of variables including opioid doses and other
co-medications were not controlled in this clinical observation, the data seem encouraging for those cancer
patients suffering from intractable neuropathic pain.

Miscellaneous Case Reports

Sporadic case reports suggest that gabapentin may be
effective in reducing pain associated with reflex sympathetic dystrophy (4), erythromelalgia (22), idiopathic trigeminal neuralgia (23), peripheral neuropathy (24,25), postthoracotomy neuropathy (26), central
pain syndromes (27,28), Guillain-Barre syndrome (29),
and taxane-induced myalgias (30). Information from
these case reports suggests that neuropathic pain with
lancinating and steady-burning quality is more likely
to respond to gabapentin as compared with pain of
other qualities.
An important issue unaddressed in the aforementioned clinical trials and case reports is the effectiveness
of gabapentin in attenuating individual symptoms
of neuropathic pain. In an open-label, nonplacebocontrolled clinical study (31), effects of gabapentin on
both spontaneous and stimulation-evoked pain were investigated in 18 patients with either peripheral or central
neuropathic pain. Responses to stimulation-evoked pain
were detected by using the quantitative sensory tests,
which included the use of mechanical (von Frey filaments) and thermal (a contact thermode) stimulation. It
was found that, at a maximum dose of 2400 mg/day,
gabapentin moderately reduced spontaneous pain, particularly spontaneous paroxysmal pain. Both tactile and
cold allodynia were reduced by gabapentin treatment.
However, gabapentin did not change pain thresholds to
either mechanical or thermal (hot) stimulation, and it did
not reduce mechanical and thermal hyperalgesia.
Several points may be mentioned from the currently
available clinical data. First, except for a few randomized, controlled clinical trials, most information regarding the efficacy of gabapentin on pain relief has
been derived from anecdotal clinical observations.
Second, gabapentin appears to be helpful in reducing
spontaneous, paroxysmal pain with burning and lancinating quality as well as allodynia to cold and tactile
stimuli. Dull, aching pain and hyperalgesia are less
likely to be responsive to gabapentin treatment. It is,

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however, not conclusive based on these reports 1) how

extensively gabapentin is being used in the clinical
practice and 2) how effectively gabapentin treatment
relieves pain conditions. Third, a common dosing
schedule from these reports involves an initial dose of
100 300 mg/day and a gradual dose escalation (100
300-mg increment every two-three days) up to a maximal tolerable dose of 2700 4800 mg/day. Fourth, the
limited clinical data suggest that pain symptoms,
rather than the etiology of pain symptoms, are likely
to be a predictive factor for a positive response to
gabapentin treatment. (See Table 1 for a summary of
clinical trial data.)

Preclinical Data
A major advantage of preclinical trials is that the effect
of gabapentin can be differentially examined on individual signs of neuropathic pain such as allodynia,
hyperalgesia, and spontaneous pain. A number of animal studies have been performed in the last several
years. The data from these studies are summarized
below based on the effect of gabapentin on nociceptive
thresholds, allodynia, and hyperalgesia.

Nociceptive Thresholds
Consistent with human studies that indicate no
changes in nociceptive thresholds by gabapentin (31),
gabapentin did not alter nociceptive thresholds in animal models of neuropathic pain (32), acute arthritic
pain (8), formalin-induced nociception (33,34), or thermal injury (35). Interestingly, gabapentin has been
reported to facilitate responses of spinal cord dorsal
horn neurons to noxious C fiber and A fiber, but not
A fiber, stimulation in normal rats (36). In sharp
contrast, gabapentin dose-dependently reduced dorsal horn neuronal responses to C fiber, but not A
fiber, stimulation in inflammatory rats three days after
the carrageenan injection (36). A similar effect of gabapentin was shown in an animal model of selective
nerve root (L5 and L6) ligation (37). These findings
suggest 1) a differential effect of gabapentin in normal
and inflammatory pain states, 2) a selective effect of
gabapentin on spinal cord neuronal responses to noxious (A and C fiber) versus innocuous (A fiber)
peripheral stimulation, and 3) an adverse (facilitatory)
effect of gabapentin on nociceptive responses of spinal
cord dorsal horn neurons in the absence of pathological pain states.

Allodynia
Allodynia to tactile or thermal stimuli could be elicited
in animals with nerve injury (32,38,39), incisional injury (7), diabetes (40), and abnormal immunoresponses to anti-GD2 ganglioside (41). Gabapentin

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given systemically reduced mechanical and/or coldinduced allodynia in each of these animal models. The
gabapentin-related compound pregabalin also reduced mechanical allodynia in diabetic rats (40). Three
observations from these studies are worth mentioning:
1) the antiallodynic dose of gabapentin did not affect
nociceptive thresholds (32); 2) although lamotrigine
(an AED) and gabapentin both decreased cold allodynia in rats with nerve injury, only gabapentin also
decreased mechanical allodynia in these same rats
(32); and 3) although systemic morphine or amitriptyline blocked static mechanical allodynia (von Frey
filament stimulation) in diabetic rats, gabapentin or
pregabalin dose-dependently blocked both static and
dynamic (lightly stroking the skin with a cotton bud)
mechanical allodynia in the same rat model (40). These
observations are consistent with a clinical study that
indicates a selective reduction of allodynia by gabapentin (31).

Hyperalgesia
Both thermal and mechanical hyperalgesia have been
shown to be reduced by systemic or intrathecal gabapentin in animal models of incisional injury (7), peripheral nerve injury (42), thermal injury (35,43), substance P-induced hyperalgesia (44), and acute arthritis
(8). Pretreatment with gabapentin also blocked the
development of hyperalgesia, suggesting a preventive
effect of gabapentin (7,8,43). The antihyperalgesic effect of gabapentin is likely to be mediated at a central
site, because intrathecal gabapentin injection produced an effect similar to that of systemic gabapentin
administration (8,35). It should be noted that, unlike
the results shown in the animal studies, both mechanical and thermal hyperalgesia were unchanged by
gabapentin in patients with neuropathic pain, as assessed by quantitative sensory tests (31).
Subcutaneous injection of formalin into a rats hind
paw elicits a two-phase response (45). This two-phase
response is unique in that the first phase (Phase 1) is
related to a normal (physiological) nociceptive process, whereas the second phase (Phase 2) may reflect a
hyperalgesic condition involving a state of central sensitization. Except for one study that reported a moderate reduction of Phase 1 nociceptive behaviors by
systemic gabapentin (46), gabapentin given either systemically or intrathecally reduced hyperalgesic behaviors only in Phase 2 of the formalin test (33,34,46,47).
Coadministration of gabapentin and formalin into the
rats hind paw itself also reduced Phase 2 hyperalgesic
behaviors (48).
In summary, the present laboratory studies indicate
that 1) gabapentin does not affect nociceptive thresholds, 2) gabapentin is effective in reducing both allodynia and hyperalgesia in animal models, and 3)

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Table 1. Summary of Clinical Trial Data

Pain Type

Study Type

Subjects

Daily Dosage

Outcome

Reference

PHN
DNP
MS
MS
CNP
Complex
DNP

Controlled
Controlled
Open-label
Open-label
Open-label
Open-label
Randomized

229
165
21
25
22
18
21

3600 mg
3600 mg
1200 mg
Various
Various
2400 mg
1565 mg

Improved VAS
Improved VAS
Pain reduction
Pain reduction
Improved VAS
Various (QST)
52% respondersa

6
5
20
18
21
31
67

PHN postherpetic neuralgia, DNP diabetic neuropathic pain, MS multiple sclerosis, CNP cancer-related neuropathic pain, Complex including
both central pain and peripheral neuropathic pain, Various including positive and negative responses to gabapentin (quantitative sensory tests), VAS visual
analog scale score.
a
Moderate-to-excellent pain relief in 52% of the participants treated with gabapentin.

gabapentin may have a selective effect on the nociceptive process involving central sensitization. Among
these findings, evidence suggesting an antiallodynic
effect of gabapentin and the lack of effect on nociceptive thresholds is consistent with that seen in clinical
studies. No data are available with regard to the effect
of gabapentin on spontaneous pain in animal models.

Potential Mechanisms of
Gabapentin Actions
Neuropathic pain is characterized by distinctive clinical symptoms and signs such as spontaneous pain,
allodynia, hyperalgesia, and pain summation. Neuropathic pain is often considered to be poorly responsive
to conventional analgesic medications, including nonsteroid antiinflammatory drugs and opioid analgesics.
Both peripheral and central mechanisms of neuropathic pain have been proposed (49,50). Peripherally,
abnormal activation of sodium channels leading to the
generation of ectopic discharges is likely to be attributable to symptoms of neuropathic pain, particularly
spontaneous, paroxysmal pain. Centrally, sensitization of spinal cord dorsal horn neurons in response to
abnormal, repetitive peripheral nociceptive input after
nerve/tissue injury plays a significant role in both
development and maintenance of neuropathic pain
symptoms. A key process of this central sensitization
is the activation of N-methyl-d-aspartate (NMDA) receptors by glutamate/aspartate within the central nervous system. In addition, an imbalance between the
spinal cord inhibitory and excitatory circuitry, presumably the result of a decreased spinal cord inhibitory (GABA) influence, may also contribute to a central hypersensitization state. Perplexingly, actions of
gabapentin on pain relief do not seem to interact with
any of these known mechanisms.
Gabapentin is ineffective in blocking sodium
channel-mediated repetitive action potentials in cultured neurons (51). Consistent with this in vitro observation, both conduction velocity and responses of Aand C-afferent fibers to noxious mechanical stimulation were not changed by gabapentin in normal rats

(39). However, IV gabapentin (30 90 mg/kg) dosedependently suppressed ectopic discharges in rats
with partial sciatic nerve ligation (39). The gabapentin
dose range effective for suppressing ectopic discharges is equivalent to that for reducing mechanical
allodynia in the same rat model (39). These findings
would suggest a selective blockade of nerve injuryinduced ectopic discharges by gabapentin, an effect
similar to that after systemic lidocaine (52). In complete contrast, gabapentin (50 mg/kg) given systemically failed to reduce ectopic discharges in a rat model
of selective nerve root ligation, although the same
dose of gabapentin was effective in attenuating mechanical allodynia (38). The results from this study
strongly argue against a peripheral effect of gabapentin on allodynia.
Gabapentin is a structural analog of GABA, which
readily crosses the blood-brain barrier when given systemically (53). Gabapentin, however, does not bind to
GABA receptors (54,55). Although gabapentin may influence the synthesis and release of GABA (55), it does
not affect the uptake and metabolism of endogenous
GABA (56,57). Importantly, the antiallodynic effect of
gabapentin is not affected by antagonists of GABA receptors (58). It is thus unlikely that the antiallodynic
effect of gabapentin, as shown in animal studies, is
caused by an enhancement of the inhibitory (GABA)
influence via its direct interaction with GABA receptors
or its indirect effect via increasing endogenous GABA.
The NMDA receptor is a molecular complex consisting of a glutamate-binding site and several regulatory sites including a strychnine-insensitive glycine
binding site. D-serine is an agonist for the NMDAglycine site. The antihyperalgesic effect of gabapentin
has been shown to be reversed by D-serine in animal
models of formalin-induced nociception (34,48), substance P- and NMDA-induced hyperalgesia (44), and
thermal injury (35). These data would suggest that
gabapentin acts as an antagonist at the NMDA-glycine
site, and D-serine competitively replaces gabapentin
thereby reversing the gabapentin effect. However, receptor binding studies fail to detect any specific interactions between gabapentin and the NMDA receptor

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complex (51,55), including the strychnine-insensitive

glycine site (59). In the absence of specific binding
data, it is unlikely that gabapentin has its effect by
means of interacting with the NMDA receptor.
A gabapentin-specific binding site was initially
identified in the central nervous system (54). This site
was later identified as the 2 subunit of voltagedependent calcium channels (60). Besides gabapentin,
S-()-3-isobutylgaba (pregabalin), but not R-()-3isobutylgaba, stereo-specifically binds to this calcium
channel subunit (60). It has been proposed that gabapentin reduces hyperalgesia by binding to this common site, because S-()-3-isobutylgaba, but not R()-3-isobutylgaba, produces similar antihyperalgesic
effects (7,43,44,47,48,61). Although voltage-dependent
calcium channels have been implicated in hyperalgesia (62), it is difficult to envision that binding to
voltage-dependent calcium channels alone by gabapentin would account for its effects on allodynia and
hyperalgesia in animal studies. In addition, the specificity of gabapentin in blocking calcium channels is
not clear. In particular, the average dose of gabapentin
used in the clinical setting is several hundred-fold
larger than that of specific calcium channel blockers.
Taken together, mechanisms of gabapentin on pain
relief remain largely elusive. Gabapentin does not directly interact with NMDA and GABA receptors. Although gabapentin modulates GABA synthesis, this
action is unlikely to be attributable because the blockade of GABA receptors does not change the gabapentins effect on allodynia. A peripheral mechanism of
gabapentin on abnormal sodium channel activation
has been proposed, but the data remain controversial.
A specific binding site (the 2 subunit of voltagedependent calcium channels) has been described for
gabapentin and pregabalin. However, a causal relationship between this gabapentin/pregabalin binding
site and pain relief is yet to be established. Animal
studies show some similarities in the reduction of
hyperalgesia between gabapentin and NMDA receptor antagonists (63). Such parallel results would suggest that the 2 subunit of voltage-dependent calcium
channels would be mechanistically critical, like the
NMDA receptor, to the development and maintenance
of hyperalgesia. Thus far, little information is available
to support this hypothesis.

Clinical Issues Concerning

Gabapentin Treatment
Pain of nonnociceptive origin including neuropathic
pain is a daily challenge both to patients and clinicians
who devote their efforts to pain management. Any
novel treatment that might provide beneficial outcomes in patients with such intractable pain will be a

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valuable addition to the current pain treatment armamentarium. Indeed, gabapentin has been regarded as
a promising new drug in pain management, although
it was initially approved by the Food and Drug Administration as an adjunctive drug for partial seizure
controls. However, several clinical issues of gabapentin should be addressed to introduce a rational use of
this drug in pain management. These issues include
the efficacy and indications, side effect profiles, and
comparisons between gabapentin and other currently
available pain medications.

Is Gabapentin an All-Purpose Painkiller?

Data from both preclinical and clinical studies clearly
demonstrate that gabapentin does not change nociceptive thresholds. Thus, gabapentin is unlikely to be a
conventional analgesic like opioids that produce analgesia by means of elevating nociceptive thresholds. No
evidence shows gabapentin to be effective in reducing
nociceptive pain. With regard to neuropathic pain, the
two controlled clinical trials (5,6) show a small but statistically significant reduction of global pain scores in
patients with DNP and PHN. These two trials, however,
used global pain scores and did not examine the effect of
gabapentin on individual pain symptoms such as spontaneous pain versus stimulation-evoked pain (allodynia,
hyperalgesia) in DNP and PHN patients. In addition,
these two trials did not assess the effects of gabapentin
on various indices of mental and physical functions.
Noncontrolled, open-label clinical studies support a
role of gabapentin in reducing spontaneous pain and
allodynia to both thermal and mechanical stimuli regardless of the etiology. Gabapentin appears particularly helpful in reducing paroxysmal pain with lancinating and burning quality in these studies. It remains
controversial whether gabapentin is effective in attenuating hyperalgesia. Much of the information regarding gabapentin in treating neuropathic pain comes
from case reports with a limited number of patients.
Yet, gabapentin is extensively used for numerous
chronic pain conditions mainly based on these anecdotal reports. One obvious shortcoming of case reports is that favorable clinical outcomes are selectively
reported without showing negative clinical experiences. Thus, the validity of these case reports should
be confirmed by controlled clinical trials.

Does Gabapentin Have Fewer Side Effects than

Other Adjunctive Pain Medications?
Gabapentin is considered to be better tolerated with
fewer side effects and minimal interactions with other
drugs. In an open-label study, the safety and tolerability of gabapentin in seizure treatment were investigated in two groups of patients receiving a daily
dose of either 1800 mg or 1800 mg (64). This study
shows that the tolerability was statistically better in

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patients receiving more than 1800 mg/day of gabapentin than those receiving 1800 mg/day, a result awaiting a plausible explanation. With regard to the safety
issue, 48.3% (2216 subjects) of the participants reported at least one of the following adverse events:
somnolence (15.2%), dizziness (10.9%), asthenia (6%),
headache (4.8%), nausea (3.2%), ataxia (2.6%), weight
gain (2.6%), and amblyopia (2.1%). A total of 10.6%
(234 of 2,216) subjects discontinued the gabapentin
therapy secondary to adverse events. The study did
not compare the safety and tolerability of gabapentin
with other commonly used AEDs, and it did not provide the outcome analysis of seizure reduction in relation to the occurrence of adverse events.
Similar side effects have been observed in pain patients treated with gabapentin. The major side effects
related to gabapentin treatment include dizziness
(24%), somnolence (23%27%), confusion (8%), and
ataxia (7%) (5,6). There are sporadic case reports of
gabapentin-induced polyneuropathy (65) and psychomotor agitation (66). Thus far, only one study directly compared the side effect profiles of gabapentin
and amitriptyline, a commonly used adjunctive pain
medication (67). This study failed to prove a better
side effect profile of gabapentin over amitriptyline. A
higher rate of sedation and dizziness was observed in
the gabapentin group, wheras a higher rate of dry
mouth was seen in the amitriptyline group. Patients in
both groups tolerated the side effects and had comparable outcomes in pain relief.

Is Gabapentin Better than Other Adjunctive

Pain Medications?
Although it is difficult to compare directly the efficacy
of different medications, the decision of choosing one
particular medication over the other should include
the consideration of outcome measures, side effect
profiles, and cost/efficiency ratios. To date, there is
only one randomized, double-blinded, cross-over
study that compared the efficacy of gabapentin and
amitriptyline on DNP pain (67). Moderate-to-great
pain relief was reported in 52% (11 of 21) patients
treated with gabapentin (a mean daily dose of 1565 mg)
and 67% (14 of 21) with amitriptyline (a mean daily dose
of 59 mg). This relatively small-scale clinical trial failed to
prove an advantageous effect of gabapentin over amitriptyline. One caveat concerning this clinical trial is that
no comparisons on individual symptoms of DNP pain
were made between gabapentin and amitriptyline treatments. Thus, it is not clear whether gabapentin would be
more effective than amitriptyline in ameliorating neuropathic pain with a certain quality, such as burning pain
and spontaneous, paroxysmal pain. The side effect profiles do not significantly differ between these two medications as discussed earlier (67). There is, however, a
remarkable cost difference between a month supply of

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gabapentin ($200 $300 with the dose range of 1800

2700 mg/day) and the generic amitriptyline ($3) and
nortriptyline ($12) (68).
In summary, gabapentin has been shown to be effective in reducing neuropathic pain associated with
DNP, PHN, MS, and cancer-related neuropathic pain.
Gabapentin appears to be helpful in reducing spontaneous, paroxysmal pain with burning and lancinating
quality as well as allodynia to cold and tactile stimuli.
Dull, aching pain and hyperalgesia are less likely to be
responsive to gabapentin treatment. The results from
preclinical studies are generally consistent with clinical findings. In particular, both clinical and preclinical
trials have clearly shown an antiallodynic effect of
gabapentin and a lack of effect on nociceptive thresholds. Although gabapentin was effective in relieving
certain neuropathic pain symptoms, thoughtfully designed, large-scale clinical trials should be performed
to confirm the efficacy of gabapentin. For example, the
effect of gabapentin on distinct symptoms and signs of
neuropathic pain should be assessed in patients with
neuropathic pain. At present, more data are needed to
support the notion that gabapentin is the first-line
treatment for neuropathic pain with a better efficacy,
fewer side effects, and a favorable cost/efficiency
ratio.

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