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Reflex sympathetic dystrophy treated with gabapentin.

The use of the recently released anticonvulsant, gabapentin (Neurontin), in the treatment of severe and refractory reflex sympathetic dystrophy (RSD) pain in six patients ranging in age from 42 to 68 years is reported. Satisfactory pain relief obtained in all six patients suggests that this medication is an effective treatment for RSD pain. In addition to pain control, early evidence of disease reversal in these patients is suggested. Patient 6 is the first documented case of successful treatment and cure of the RSD pain syndrome using gabapentin alone. Specifically, reduced hyperpathia, allodynia, hyperalgesia, and early reversal of skin and soft tissue manifestations were noted. Gabapentin was chosen because it has properties similar to other anticonvulsant drugs and because previous studies have shown that it is well tolerated and appears to have a benign efficacy-to-toxicity ratio. It was considered an acceptable and compassionate therapeutic choice because previous medical and surgical approaches had been ineffective for these patients, who represent the first case series documenting the use of gabapentin for pain management. Presently, the mechanism of pain relief in these patients is unknown. In this article, the pathophysiology of RSD is discussed, and a mechanism by which gabapentin provides pain relief is proposed. In view of encouraging results in these and other RSD patients, further scientific investigation is needed to delineate the role of gabapentin in the treatment of reflex sympathetic dystrophy.

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Inhibition of neuronal Ca(2+) influx by gabapentin and pregabalin in the human neocortex.

Gabapentin and pregabalin (S-(+)-3-isobutylgaba) produced concentration-dependent inhibitions of the K(+)-induced [Ca(2+)](i) increase in fura-2-loaded human neocortical synaptosomes (IC(50)=17 microM for both compounds; respective maximal inhibitions of 37 and 35%). The weaker enantiomer of pregabalin, R-(-)-3-isobutylgaba, was inactive. These findings were consistent with the potency of these drugs to inhibit [(3)H]-gabapentin binding to human neocortical membranes. The inhibitory effect of gabapentin on the K(+)-induced [Ca(2+)](i) increase was prevented by the P/Q-type voltage-gated Ca(2+) channel blocker omega-agatoxin IVA. The alpha 2 delta-1, alpha 2 delta-2, and alpha 2 delta-3 subunits of voltage-gated Ca(2+) channels, presumed sites of gabapentin and pregabalin action, were detected with immunoblots of human neocortical synaptosomes. The K(+)-evoked release of [(3)H]-noradrenaline from human neocortical slices was inhibited by gabapentin (maximal inhibition of 31%); this effect was prevented by the AMPA receptor antagonist NBQX (2,3-dioxo-6-nitro-1,2,3,4-tetrahydro[f]quinoxaline-7-sulphonamide). Gabapentin and pregabalin may bind to the Ca(2+) channel alpha 2 delta subunit to selectively attenuate depolarization-induced Ca(2+) influx of presynaptic P/Q-type Ca(2+) channels; this results in decreased glutamate/aspartate release from excitatory amino acid nerve terminals leading to a reduced activation of AMPA heteroreceptors on noradrenergic nerve terminals.

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Use of gabapentin for postherpetic neuralgia: results of two randomized, placebo-controlled studies.

BACKGROUND: Postherpetic neuralgia (PHN), which affects up to 70% of elderly persons with herpes zoster, can have debilitating effects, including physical and social disability and significant psychological distress. A variety of agents have been used, either singly or in combination, to control PHN, including topical and oral analgesics, antidepressants, and antiepileptic drugs (AEDs). However, PHN often proves refractory to these therapies. OBJECTIVE: This article reviews available data on the use of the newer AED gabapentin for the control of PHN. METHODS: A MEDLINE search was undertaken to identify all randomized, placebo-controlled trials on the use of gabapentin in PHN. The search terms were gabapentin and postherpetic neuralgia. RESULTS: The literature search identified 2 published studies of the efficacy of gabapentin in a total of 563 patients with PHN that had persisted for at least 3 months after the healing of herpes zoster rash. The studies employed multiple outcome measures, including visual analog and Likert scales for pain intensity, and quality-of-life and functional measures that included the Medical Outcomes Study 36-item Short Form Health Survey (SF-36) and the Profile of Mood States. At maximum target dosages of 1800 to 3600 mg/d, gabapentin produced significant reductions in mean daily pain scores compared with placebo on both visual analog(P < 0.001) and Likert scales (P < 0.01). Improvements were also seen on the SF-36 subscales for physical functioning, bodily pain, vitality, and mental health(P < 0.01). CONCLUSION: Gabapentin may provide benefits in terms of alleviation of pain and overall quality of life in patients with chronic PHN.

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Gabapentin treatment of the non-refractory bipolar spectrum: an open case series.

OBJECTIVE: To determine if gabapentin is effective in monotherapy or add-on treatment of non-refractory bipolar disorder in open prospective treatment. METHODS: Charts of 21 outpatients meeting DSM-IV criteria for bipolar spectrum disorder (type I, type II, NOS, and cyclothymia) and who were treated with gabapentin were reviewed and clinical response was assessed based on prospective application of the Hamilton Depression Rating Scale (HDRS), the Young Mania Rating Scale (YMRS), the Clinical Global Impression scale (CGI), and the Global Assessment of Functioning scale (GAF). Also, response was rated retrospectively using the Clinical Global Impression scale for Bipolar Disorder (CGI-BP). RESULTS: Eight patients received gabapentin monotherapy and 13 received adjunctive therapy. Similar improvement in depression was noted in the monotherapy group, without induction of mania. Gabapentin was associated with a 43.8% improvement in manic symptoms and a 27.6% improvement in depressive symptoms in the overall sample. In the depressed subsample (n=10), there was a 57.5% improvement in depressive symptoms (P=0.10). Using the CGI-BP, gabapentin was moderately to markedly effective in 43% of patients for overall bipolar illness, 38% for depressive symptoms, and 25% for manic symptoms. Of those in the study, 62% reported side effects, mainly sedation and nausea, with 14% of the total sample discontinuing treatment due to adverse events. CONCLUSIONS: Gabapentin, either alone or as an adjunct, appeared moderately effective in treating depression in this small, uncontrolled, heterogeneous sample of non-refractory bipolar spectrum illness. Coupled with the earlier clinical literature, these data suggest the need for prospective double-blind studies of depressive illness in the bipolar spectrum.

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Open maintenance treatment of bipolar disorder spectrum patients who responded to gabapentin augmentation in the acute phase of treatment.

This report describes the results of maintenance treatment with gabapentin in 18 previously refractory Bipolar Disorder patients who initially responded to augmentation with gabapentin during the acute phase of their therapy. Seven of the original 18 patients (39%) have continued to experience benefit from maintenance gabapentin treatment. Only three patients had to discontinue the gabapentin because of side effects. None of the 18 patients experienced an obvious significant adverse drug-drug interaction. Five of the patients discontinued gabapentin because of diminished clinical efficacy after a significant period of positive therapeutic effect. The results of this small open study suggest that gabapentin may be effective as an augmenting agent in the maintenance phase of treatment of some bipolar spectrum patients.

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Repeated administration of systemic gabapentin alleviates allodynia-like behaviors in spinally injured rats.

The effect of systemic gabapentin, a novel antiepileptic and analgesic, was tested on allodynia-like behaviors in spinal cord injured rats. On the first day of treatment 30 mg/kg intraperitoneal gabapentin did not alleviate hyper-reactivity to mechanical and cold stimulation. The allodynia was significantly reduced by 100 mg/kg gabapentin, which however, produced sedation and motor impairments. Repeated administration of 30 mg/kg gabapentin once a day produced a gradually increasing anti-allodynic effect. Total alleviation of mechanical allodynia was observed in most rats after the third administration of gabapentin. Thus, build-up of the antiallodynic effect of gabapentin may develop through a time dependent mechanism or alternatively through a gradual accumulation of the effective central nervous system concentration of the drug.

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Gabapentin in postherpetic neuralgia: a randomised, double blind, placebo controlled study.

A multicentre double blind, randomised, placebo controlled 7-week study evaluated the efficacy and safety of gabapentin 1800 or 2400 mg/day in treating postherpetic neuralgia. Three hundred and thirty-four men and women aged at least 18 years (mean 73) received gabapentin 1800 or 2400 mg daily or placebo in three divided doses with a forced titration schedule. The primary outcome measure was change in average daily pain diary score (baseline week v final week). Secondary outcomes included mean weekly sleep interference score; Short Form-McGill Pain Questionnaire (SF-MPQ); Clinician and Patient Global Impression of Change (CGIC/PGIC); Short Form-36 Health Survey (SF-36). From week 1, pain scores showed a significantly greater improvement with gabapentin: the final difference v baseline was -34.5% for the 1800 mg dose, -34.4% for the 2400 mg dose compared with -15.7% for the placebo group. The difference vs. placebo was 18.8% for the 1800 mg dose (95% confidence interval 10.9-26.8%; P<0.01) and 18.7% for the 2400 mg dose (10.7-26.7%; P<0.01). Sleep interference diaries showed a similar pattern. There were significant differences in favour of gabapentin for number of patients reporting >50% reduction in their pain intensity, in the CGIC and PGIC, in the sensory and total scores of the SF-MPQ (both doses), in the visual analogue scale of pain of the SF-MPQ (2400 mg only) and in the vitality, bodily pain and mental health domains of the SF-36. Overall gabapentin was well tolerated. The most common adverse events were dizziness and somnolence, particularly during the titration phase. Thus, this study confirms the role of gabapentin as an efficacious and well-tolerated treatment for postherpetic neuralgia.

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Effects of systemic carbamazepine and gabapentin on spinal neuronal responses in spinal nerve ligated rats.

There are few pharmacological studies of central neuronal measures in animal models of neuropathic pain. In the present study we have compared the effects of two anticonvulsants, carbamazepine and gabapentin, on spinal neuronal responses of nerve injured rats (selective ligation of spinal nerves L5 and L6, SNL) and sham-operated rats. The development and maintenance of cooling and mechanical allodynia of the lesioned hindlimb of SNL rats was followed with behavioural indices. The contralateral hindlimb of SNL rats and the ipsilateral hindlimb of sham-operated rats did not develop allodynia. Electrophysiological studies of SNL rats were then performed at two post-operative (PO) time points (PO days 7-10 and PO days 14-17). Spinal neurones of SNL rats, but not sham-operated rats, exhibited spontaneous activity at both PO days 7-10 and 14-17 (1 +/- 0.4 and 3 +/- 1 Hz, respectively). Paradoxically, the magnitude of electrical (C-fibre) and natural (mechanical and thermal) evoked neuronal responses of SNL rats at PO days 14-17 were smaller than the evoked neuronal responses of SNL rats at PO days 7-10 and sham-operated rats. The electrical evoked A-fibre responses of neurones were comparable for the three groups of rats. Both subcutaneous carbamazepine (0.5-22.5 mg/kg) and gabapentin (10-100 mg/kg) significantly reduced the spontaneous activity of spinal neurones of SNL rats at both PO time points. Carbamazepine had inhibitory effects on electrical C- and A-fibre and mechanical punctate (9 and 50 g) evoked neuronal responses of SNL rats which were significantly different to the lack of effect of carbamazepine on these measures in sham-operated rats. Gabapentin had comparable effects as carbamazepine on the electrical C-and A-fibre and mechanical punctate (9 and 50 g) evoked neuronal responses of SNL rats. In contrast to carbamazepine, gabapentin also reduced evoked neuronal responses of sham-operated rats and there was no difference between the effects of gabapentin in SNL and sham-operated rats. Robust behavioural changes in the SNL model of neuropathy are paralleled by a temporal increase in spontaneous activity and a paradoxical decrease in evoked spinal neuronal responses. The peripheral nerve dysfunction reveals an effect of carbamazepine which is maintained throughout the observation period, validating this experimental approach. Gabapentin, a novel treatment for neuropathic pain states, also reduced neuronal responses, but the actions of the drug were not dependent on nerve injury. Further studies at the spinal level may shed light on the physiology and pharmacology of the aberrant processes associated with neuropathic pain.

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Development of two stable oral suspensions for gabapentin.

Gabapentin is not available in a liquid dosage form for clinical use. This study was designed to develop two oral gabapentin suspensions and determine their stability under refrigeration or at room temperature. Commercially available gabapentin capsules were used to prepare two suspensions: one in extemporaneously prepared 1% methylcellulose in syrup (1:1) and another in equal volumes of commercially available suspending agents/syrup (Ora Plus/Ora Sweet). Each suspension containing gabapentin (100 mg/mL) was stored in 10 plastic prescription bottles; five were stored at 4 degrees C and five at 25 degrees C. Three 500-microL samples were collected immediately after preparation (day 0) and on days 7, 14, 28, 42, 56, 70, and 91. Gabapentin was measured by accurate, reproducible, specific, and stability-indicating high-performance liquid chromatography (n = 15). The observed mean concentrations exceeded 90% of the initial concentrations in both suspensions for 91 days at 4 degrees C and 56 days at 25 degrees C. No change in pH, odor, or physical appearance was observed. On the basis of these results, stable oral suspensions of gabapentin can be prepared and stored in plastic prescription bottles for 91 days at 4 degrees C or 56 days at 25 degrees C.

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The effects of gabapentin on different ligand- and voltage-gated currents in isolated cortical neurons.

A clear picture of the mechanisms of action of the anti-epileptic agent gabapentin is far from being accomplished. We have analyzed the effects of gabapentin on ligand- and voltage-gated currents in isolated adult rat cortical neurons. Gabapentin failed to modify glutamate currents and produced a slight reduction of GABA responses. Negligible inhibition of sodium, but consistent inhibition of high-voltage-activated calcium conductance was promoted by gabapentin. In addition, gabapentin reduced calcium current sensitivity to dihydropyridine agonist and antagonists. Interestingly, gabapentin also decreased a not-inactivating, cadmium-sensitive, potassium current. These unconventional effects might underlie its efficacy in a variety of diseases which involve periodic discharge patterns as neuropathic pain or essential tremor.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Experience with gabapentin for neuropathic pain in the head and neck: report of ten cases.

BACKGROUND AND OBJECTIVES: Gabapentin is an oral antiepileptic agent with an unknown mechanism of action. Recent case reports have suggested that gabapentin may be effective in the treatment of a variety of neuropathic pain states. This report presents baseline and follow-up data on ten patients who were treated with gabapentin when other pharmacologic interventions failed to relieve their neuropathic pain. METHODS: Ten patients referred for treatment of unrelieved neuropathic pain in the head and neck region were included in this study. Baseline and follow-up information included measures of pain intensity and pain quality. All of the patients were started on 300 mg gabapentin three times per day, though daily doses of up to 2400 mg were required for pain relief. RESULTS: Eight of the ten patients had no neuropathic pain on follow-up, whereas the remaining 2 patients reported only partial relief at follow-up. None of the patients complained of side effects. Gabapentin was effective in alleviating steady burning pain as well as lancinating pain and allodynia. CONCLUSIONS: The results suggest that gabapentin may be effective in the management of some cases of neuropathic pain in the head and neck. However, controlled, double-blind longitudinal studies are needed to evaluate this possibility.

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Gabapentin reduces cardiovascular responses to laryngoscopy and tracheal intubation.

BACKGROUND AND OBJECTIVE: We have compared the effects of gabapentin on arterial pressure and heart rate at induction of anaesthesia and tracheal intubation in a randomized double-blind study. METHODS: Ninety normotensive patients (ASA I) undergoing elective surgery were divided into three groups of 30 patients each. Patients received oral placebo (Group I), 400 mg of gabapentin (Group II) or 800 mg of gabapentin (Group III) 1 h prior to surgery in the operating theatre. After induction of anaesthesia heart rate and mean arterial pressure were recorded at baseline 1, 3, 5, 10 and 15 min after intubation. RESULTS: Patients receiving placebo and 400 mg gabapentin showed a significant increase in blood pressure and heart rate associated with tracheal intubation compared to baseline levels and Group III. There was significant decrease in heart rate and arterial pressure in Group III after intubation 1, 3, 5 and 10 min (P < 0.001, P < 0.001, P < 0.05 and P < 0.05, respectively) compared to Groups I and II. CONCLUSION: Given 1 h before operation gabapentin 800 mg blunted the arterial pressure and heart rate increase in first 10 min due to endotracheal intubation. Oral administration of gabapentin 800 mg before induction of anaesthesia is a simple and practical method for attenuating pressor response to laryngoscopy and tracheal intubation after standard elective induction.

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Gabapentin.

Gabapentin is a novel antiepileptic drug that has recently been introduced in Canada. Although its mechanism of action remains to be defined gabapentin is effective in a number of seizure models which predict its efficacy in partial and tonic-clonic seizures. Clinical studies support the clinical efficacy of gabapentin as adjunctive therapy in adults with epilepsy with partial and secondarily generalized tonic-clonic seizures. Gabapentin has a favorable pharmacokinetic profile and is generally well tolerated. More clinical data are required on the role of gabapentin in children and additional monotherapy experience is required before the role of gabapentin in the overall treatment of epilepsy can be better defined.

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Gabapentin in PTSD: a retrospective, clinical series of adjunctive therapy.

Posttraumatic stress disorder (PTSD) symptoms may improve significantly with antidepressant medications, however some phenomena often remain refractory to the most commonly used treatments. Frequently, sleep disturbances, such as insomnia and nightmares, are symptoms of PTSD that are refractory to antidepressant treatment. Gabapentin, a novel anticonvulsant agent, has been of interest as a potential anxiolytic agent, but has not been evaluated in PTSD. We reviewed records of 30 consecutive patients who had been diagnosed with PTSD according to structured interviews and had received gabapentin as an adjunctive medication. For each patient, the target symptoms that led to the initiation of gabapentin treatment were identified. Using the most recent clinical data available, the change in target symptom severity following treatment was rated as unimproved, mildly improved, moderately improved, or markedly improved. The gabapentin was often first prescribed to facilitate sleep. The majority (77%) of patients showed moderate or greater improvement in duration of sleep, and most noted a decrease in the frequency of nightmares. The dose range was 300-3600 mg/day. Sedation and mild dizziness were the most commonly reported side effects. This retrospective study suggests that gabapentin may improve in particular sleep difficulties and also other symptoms associated with chronic PTSD. Prospective, controlled studies are needed to further investigate the effects of gabapentin on insomnia, nightmares, and other core PTSD symptoms.

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Adverse effects of gabapentin and lack of anti-allodynic efficacy of amitriptyline in the streptozotocin model of painful diabetic neuropathy.

Amitriptyline and gabapentin are the primary treatments for painful diabetic neuropathy (PDN), and it is clear that they produce beneficial effects, but there are questions about these treatments that have not been adequately addressed. For example, although there is a growing consensus that the therapeutic effects of amitriptyline in pain patients are independent of its effects on mood, it is not clear that amitriptyline has specific and direct effects on pain. There is also a fairly broad consensus that gabapentin is safe and well tolerated, but the side-effect profile of gabapentin has not been adequately assessed in pain populations. The rat streptozotocin (STZ) model of PDN was used (a) to assess the effects of amitriptyline on objective, quantitative measures of tactile allodynia, a common type of pain in PDN patients, and (b) to assess the side effects of gabapentin using measures of motor/ambulatory and cognitive function. Amitriptyline did not attenuate STZ-induced mechanical allodynia, even after chronic administration of high doses. Gabapentin produced robust anti-allodynic effects but also produced deficits in tests of motor/ambulatory and cognitive functions. The present experiments suggest that the beneficial effects of amitriptyline in PDN may not be a result of anti-allodynic efficacy and that gabapentin produces robust anti-allodynic effects but may also produce significant motor and cognitive deficits even at or near the lowest effective doses. These findings challenge the consensus opinions about these primary treatments for PDN and suggest that their therapeutic and adverse effects should be explored further in pain patients.

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A comparison of Ca2+ channel blocking mode between gabapentin and verapamil: implication for protection against hypoxic injury in rat cerebrocortical slices.

1 The mode of Ca(2+) channel blocking by gabapentin [1-(aminomethyl)cyclohexane acetic acid] was compared to those of other Ca(2+) channel blockers, and the potential role of Ca(2+) channel antagonists in providing protection against hypoxic injury was subsequently investigated in rat cerebrocortical slices. 2 mRNA for the alpha(2)delta subunits of Ca(2+) channels was found in rat cerebral cortex. 3 Nitric oxide (NO) synthesis estimated from cGMP formation was enhanced by KCl stimulation, which was mediated primarily by the activation of N- and P/Q-type Ca(2+) channels. Gabapentin blocked both types of Ca(2+) channels, and preferentially reversed the response to 30 mM K(+) stimulation compared with 50 mM K(+) stimulation. In contrast, verapamil preferentially inhibited the response to depolarization by the higher concentration (50 mM) of K(+). 4 Gabapentin inhibited KCl-induced elevation of intracellular Ca(2+) in primary neuronal culture. 5 Hypoxic injury was induced in cerebrocortical slices by oxygen deprivation in the absence (severe injury) or presence of 3 mM glucose (mild injury). Gabapentin preferentially inhibited mild injury, while verapamil suppressed only severe injury. omega-Conotoxin GVIA (omega-CTX) and omega-agatoxin IVA (omega-Aga) were effective in both models. 6 NO synthesis was enhanced in a manner dependent on the severity of hypoxic insults. Gabapentin reversed the NO synthesis induced by mild insults, while verapamil inhibited that elicited by severe insults. omega-CTX and omega-Aga were effective in both the cases. 7 Therefore, the data suggest that gabapentin and verapamil cause activity-dependent Ca(2+) channel blocking by different mechanisms, which are associated with their cerebroprotective actions and are dependent on the severity of hypoxic insults.

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Reduction by gabapentin of K+-evoked release of [3H]-glutamate from the caudal trigeminal nucleus of the streptozotocin-treated rat.

Recently, we showed that gabapentin can inhibit a facilitatory effect of substance P (SP) on K(+)-evoked glutamate release in rat trigeminal slices (Maneuf et al., 2001), and we have now examined the effect of gabapentin on glutamate release in the trigeminal slice from the streptozotocin (STZ)-treated rat. 1. At 4 weeks following STZ treatment (50 mg kg(-1) i.p.), blood glucose was increased in the majority of cases, compared to the control level. All the treated animals showed a significant degree (P<0.001) of tactile allodynia (assessed using von Frey filaments) that did not appear to correlate with blood glucose levels. 2. In this study, we demonstrated that, after STZ treatment, 30 microM gabapentin reduced K(+)-evoked release of [(3)H]-glutamate in either normal (11 mM) or high (30 mM) glucose conditions by 24 and 22%, respectively. In the normal rat, gabapentin (up to 100 microM) is ordinarily unable to affect release of glutamate from the trigeminal slice. 3. The uptake of glutamate in Sp5C punches from streptozotocin-treated rats was reduced under normal glucose conditions (41.7% of control), whereas high glucose restored uptake to normal (84.7% of control). 4. The addition of 1 microm substance P potentiated the evoked release of glutamate in both normal (40% increase) and high glucose (28%), and this was blocked by gabapentin (30 microM) in both conditions. It is interesting to speculate that this ability of gabapentin to reduce the release of glutamate in the trigeminal nucleus after streptozotocin treatment may be of relevance to the antihyperalgesic-allodynic actions of the drug.

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A nitric oxide (NO)-releasing derivative of gabapentin, NCX 8001, alleviates neuropathic pain-like behavior after spinal cord and peripheral nerve injury.

1. Nitric oxide (NO) participates, at least in part, to the establishment and maintenance of pain after nerve injury. Therefore, drugs that target the NO/cGMP signaling pathway are of interest for the treatment of human neuropathic pain. Various compounds endowed with NO-releasing properties modulate the expression and function of inducible nitric oxide synthase (iNOS), the key enzyme responsible for sustained NO production under pathological conditions including neuropathic pain. 2. With this background, we synthesized a new chemical entity, [1-(aminomethyl)cyclohexane acetic acid 3-(nitroxymethyl)phenyl ester] NCX8001, which has a NO-releasing moiety bound to gabapentin, a drug currently used for the clinical management of neuropathic pain. We examined the pharmacological profile of this drug with respect to its NO-releasing properties in vitro as well as to its efficacy in treating neuropathic pain conditions (allodynia) consequent to experimental sciatic nerve or spinal cord injuries. 3. NCX8001 (1-30 microm) released physiologically relevant concentrations of NO as it induced a concentration-dependent activation of soluble guanylyl cyclase (EC(50)=5.6 microm) and produced consistent vasorelaxant effects in noradrenaline-precontracted rabbit aortic rings (IC(50)=1.4 microm). 4. NCX8001, but not gabapentin, counteracted in a concentration-dependent fashion lipopolysaccharide-induced overexpression and function of iNOS in RAW264.7 macrophages cell line. Furthermore, NCX8001 also inhibited the release of tumor necrosis factor alpha (TNFalpha) from stimulated RAW264.7 cells. 5. NCX8001 (28-280 micromol x kg(-1), i.p.) reduced the allodynic responses of spinal cord injured rats in a dose-dependent fashion while lacking sedative or motor effects. In contrast, gabapentin (170-580 micromol x kg(-1), i.p.) resulted less effective and elicited marked side effects. 6. NCX8001 alleviated the allodynia-like responses of rats to innocuous mechanical or cold stimulation following lesion of the sciatic nerve. This effect was not shared by equimolar doses of gabapentin. 7. Potentially due to the slow releasing kinetics of NO, NCX8001 alleviated pain-like behaviors in two rat models of neuropathic pain in a fashion that is superior to its parent counterpart gabapentin. This new gabapentin derivative, whose mechanism deserves to be explored further, offers new hopes to the treatment of human neuropathic pain.

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