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PubMedDate not supplied

Gabapentin produces dose-dependent antinociception in the orofacial formalin test in the rat.

BACKGROUND AND OBJECTIVES: High neuraxial drug infusion has been advocated for the treatment of intractable cranial and facial pain in humans. Currently, parallel animal models have not been characterized to support this methodology. We combined an accepted animal model of pain of cranial origin with a novel technique of cervico-medullary drug delivery to determine the antinociceptive potential of gabapentin. Gabapentin was chosen because of its reported efficacy in a wide array of complex cranial pain syndromes. METHODS: Male Wistar rats were implanted with intrathecal catheters that were advanced cephalad through a lumbar guide cannula to terminate in the high cervical spinal cord (C1-C4). Antinociception was assessed by the orofacial formalin test. Vehicle or gabapentin (3, 10, 30, 100 microg) was injected intrathecally followed 10 minutes later by injection of 2.5% formalin solution into the vibrissal pad. Motor assessment was evaluated in a separate group of animals. RESULTS: Intrathecal gabapentin (10, 30, 100 microg) produced a dose-dependent decrease in the second phase of the behavioral response to formalin (P <.05). First-phase responses were unaffected by all doses of gabapentin. The ED50 (95% confidence limit) value for the second phase was 8.27 microg (3.50 to 14.5). No overt motor dysfunction or behavioral impairment was observed. CONCLUSIONS: Gabapentin produced dose-dependent antinociception in the second phase of the orofacial formalin test in the rat after injection into the cervico-medullary cerebrospinal fluid. This animal model may be useful to assess analgesics designed for parallel clinical application in humans for the treatment of intractable head and neck pain that is refractory to conventional modalities.

Acetates↗
PubMedDate not supplied

Gabapentin in postamputation phantom limb pain: a randomized, double-blind, placebo-controlled, cross-over study.

BACKGROUND AND OBJECTIVES: Severe phantom limb pain after surgical amputation affects 50% to 67% of patients and is difficult to treat. Gabapentin is effective in several syndromes of neuropathic pain. Therefore, we evaluated its analgesic efficacy in phantom limb pain. METHODS: Patients attending a multidisciplinary pain clinic with phantom limb pain were enrolled into this randomized, double-blind, placebo-controlled, cross-over study. Other anticonvulsant therapy was discontinued. Each treatment was 6 weeks separated by a 1-week washout period. Codeine/paracetamol was allowed as rescue analgesia. The daily dose of gabapentin was titrated in increments of 300 mg to 2400 mg or the maximum tolerated dose. Patients were assessed at weekly intervals. The primary outcome measure was visual analog scale (VAS) pain intensity difference (PID) compared with baseline at the end of each treatment. Secondary measures were indices of sleep interference, depression (Hospital Anxiety and Depression [HAD] scale), and activities of daily living (Bartel Index). RESULTS: Nineteen eligible patients (mean age, 56 years; range, 24 to 68 years; 16 men) were randomized, of whom 14 completed both arms of the study. Both placebo and gabapentin treatments resulted in reduced VAS scores compared with baseline. PID was significantly greater than placebo for gabapentin therapy at the end of the treatment (3.2 +/- 2.1 v 1.6 +/- 0.7, P =.03). There were no significant differences between placebo and gabapentin therapy in terms of the number of tablets of rescue medication required, sleep interference, HAD scale, or Bartel Index. The medication was well tolerated with few reports of adverse effects. CONCLUSIONS: After 6 weeks, gabapentin monotherapy was better than placebo in relieving postamputation phantom limb pain. There were no significant differences in mood, sleep interference, or activities of daily living, but a type II error cannot be excluded for these variables.

Acetates↗
PubMed1999

Clinical experience using adjunctive gabapentin in treatment-resistant bipolar mixed states.

OBJECTIVE: Open studies and case observations have suggested that gabapentin may be effective in the treatment of bipolar disorder. However, the adjunctive use of the drug in bipolar mixed states has not been specifically addressed before. METHODS: Twenty-one patients with bipolar I mixed episodes as defined by Diagnostic and Statistical Manual of Mental Disorders (Revised) (DSM-III-R), who were admitted to the outpatient department at the Psychiatry Clinic of the University of Pisa, were treated adjunctively with gabapentin for a period of eight weeks. All patients had been resistant to therapeutic levels of standard mood stabilizers, and had a mean clinical global impression (CGI) of 5.2+/-0.8 when entering the study. Gabapentin treatment was started at 300 mg/day and increased up to 2000 mg/day. Patients were evaluated using the Hamilton Rating Scale for Depression (HRSD), the Young Mania Rating Scale (YMRS), and CGI. Patients with final CGI scores of 1 or 2 were regarded as responders. RESULTS: Only one patient had to interrupt the drug treatment, due to irritability and ataxia. Negative interactions between gabapentin and concomitant psychotropic medications were not observed. The condition deteriorated in only one patient (final CGI = 5). Ten patients were regarded as responders: four showed marked improvement (CGI = 1), and six had moderate improvement (CGI = 2). The mean dose of gabapentin at week 8 was 1130 mg (range 600-2000 mg). The mean final CGI score for all patients (responders and nonresponders combined) was 3.7+/-1.1 (the mean change in CGI was significant, t=6.1, P<0001). The reduction in the mania score was minimal and statistically insignificant. However, the mean HRSD score showed a statistically significant reduction from 18.2 to 10.6 (t=5.73, P<0.0001), irrespective of the baseline severity of the mania. All but one of the responders maintained these therapeutic improvements over 4-12 months, in most cases requiring less concomitant antidepressant and neuroleptic medications. CONCLUSIONS: These results show that gabapentin appears to be potentially useful in the adjunctive treatment of drug-resistant bipolar mixed states, and that it was particularly effective in relation to depressive symptomatology.

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PubMed1996

The novel anticonvulsant drug, gabapentin (Neurontin), binds to the alpha2delta subunit of a calcium channel.

Gabapentin (1-(aminomethyl)cyclohexane acetic acid; Neurontin) is a novel anticonvulsant drug, with a mechanism of action apparently dissimilar to that of other antiepileptic agents. We report here the isolation and characterization of a [3H]gabapentin-binding protein from pig cerebral cortex membranes. The detergent-solubilized binding protein was purified 1022-fold, in a six-step column-chromatographic procedure, with a yield of 3.9%. The purified protein had an apparent subunit Mr of 130,000, and was heavily glycosylated. The partial N-terminal amino acid sequence of the Mr 130,000 polypeptide, EPFPSAVTIK, was identical to that reported for the alpha2delta subunit of the L-type Ca2+ channel from rabbit skeletal muscle (Hamilton, S. L., Hawkes, M. J., Brush, K., Cook, R., Chang, R. J., and Smilowitz, H. M. (1989) Biochemistry 28, 7820-7828). High levels of [3H]gabapentin binding sites were found in membranes prepared from rat brain, heart and skeletal muscle. Binding of [3H]gabapentin to COS-7 cells transfected with alpha2delta cDNA was elevated >10-fold over controls, consistent with the expression of alpha2 delta protein, as measured by Western blotting. Finally, purified L-type Ca2+ channel complexes were fractionated, under dissociating conditions, on an ion-exchange column; [3H]gabapentin binding activity closely followed the elution of the alpha2 delta subunit. [3H]Gabapentin is the first pharmacological agent described that interacts with an alpha2delta subunit of a voltage-dependent Ca2+ channel.

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PubMed2003

Characterization of gabapentin overdose using a poison center case series.

BACKGROUND: Gabapentin is an anticonvulsant that is being used for an increasing number of off-label indications. The purpose of this study is to document the clinical manifestations and outcomes of gabapentin exposures reported to poison centers. METHODS: A multicenter prospective observational study of all gabapentin exposures reported to three poisoncenters was conducted between 4/1/98 and 4/1/2000. Cases involving gabapentin only were evaluated. RESULTS: There were 20 cases with gabapentin as the sole substance in doses ranging from 50 mg to 35 g. Ten of the 20 cases involved children and adolescents. Clinical effects developed early and resolved within 10 hours in most patients. Seven cases were managed in the home with only observation. Four of these patients remained asymptomatic. Effects reported in the three symptomatic patients were drowsiness (3) and ataxia (1). Thirteen patients were managed in a health care facility. Nine were symptomatic with reported effects of drowsiness (6), dizziness (3), nausea/vomiting (2), tachycardia (2), and hypotension (2). None of the patients were admitted for medical care. CONCLUSION: In this cases series, gabapentin exposures caused no or minimal toxicity.

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PubMed2004

Gabapentin versus levodopa for the treatment of Restless Legs Syndrome in hemodialysis patients: an open-label study.

BACKGROUND: Restless Legs Syndrome (RLS), a common problem increasing morbidity and mortality in hemodialysis (HD) patients, affects 20-30% of uremic patients. Our aim was to find the efficacy of gabapentin in the treatment of RLS in HD patients by comparing a largely used drug, levodopa. METHODS: Patients with RLS answered three questionnaires (RLS rating scale proposed by IRLSSG, the Short Form (SF)-36 and the Pittsburgh Sleep Quality Index) for the evaluation of severity of RLS, effects on quality of life and quality of sleep. RESULTS: Fifteen patients (4.7%) (5 F, 10 M) with a mean age of 45.8+/-15.3 years got RLS diagnosis. When we compare the two drugs for severity of RLS symptoms relief, the effect of gabapentin was more significant (p<0.001). Gabapentin significantly improved general health, body pain and social functions (p<0.001). Moreover, regarding sleep parameters, gabapentin was significantly superior to levodopa for sleep quality, sleep latency (p<0.001) and sleep disturbance (p<0.000). CONCLUSION: To our knowledge this was the first study comparing gabapentin and levodopa efficacy for the treatment of RLS in HD patients. Our results suggested that gabapentin is an effective drug for the management of RLS in hemodialysis patients.

Adult↗
PubMed2001

Gabapentin and methylphenidate treatment of a preadolescent with attention deficit hyperactivity disorder and bipolar disorder.

Gabapentin is an anticonvulsant drug released in the United States in 1993 for use as adjunctive therapy in refractory partial epilepsy. The mechanism of action of gabapentin is unknown, but the drug has very favorable pharmacokinetics and a good safety profile, which allows its use in high-risk patients. Several reports have described the successful use of gabapentin for bipolar disorders in adults, but there are no controlled studies in the use of gabapentin in children and adolescents. We describe a 12-year-old boy with a history of attention deficient hyperactivity disorder (ADHD), reading disorder, mixed receptive and expressive language disorder, encopresis, and bipolar disorder II who was treated with gabapentin 200 mg/day added to methylphenidate 30 mg/day. Within 3 weeks the improvement and stabilization of mood symptoms was remarkable, as noted by mother, teacher, and clinician, and remained so for 6 months of follow-up. Comorbid bipolar disorder and ADHD is a hotly debated topic in the child and adolescent psychiatric literature, with rates of comorbid ADHD and bipolar disorder ranging from 22% to 90%. Controlled studies are needed to evaluate the possible antimanic mood stabilizing and/or antidepressant properties or gabapentin in youths.

Acetates↗
PubMed1998

Gabapentin in the treatment of adolescent mania: a case report.

Gabapentin is a new antiepileptic drug with an unknown mechanism of action and very favorable pharmacokinetic and safety profiles. An increasing number of reports have described the successful use of gabapentin in bipolar disorder in adults. A 13-year-old boy with bipolar I disorder, manic episode, and ADHD, was treated with gabapentin 1,500 mg/day as add-on therapy to carbamazepine and showed a marked response within 1 month. He had previously failed a divalproex trial, could not tolerate lithium, and carbamazepine could not control his symptoms and induced a low WBC. He remained euthymic 7 months after gabapentin was added. His Young Mania Rating Scale (YMRS) score was 27 when gabapentin was added, 9 after 1 month, 15 after 4 months, and 6 after 7 months. Controlled studies are needed to evaluate the possible anti-manic, mood stabilizing, and/or anti-depressant properties of gabapentin in youth.

Acetates↗
PubMed2004

Gabapentin therapy for pruritus in haemodialysis patients: a randomized, placebo-controlled, double-blind trial.

BACKGROUND: Uraemic pruritus is a common and distressing symptom in patients on haemodialysis for chronic renal failure. Gabapentin is an anticonvulsant that alleviates neuropathic pain. We conducted a double-blind, placebo-controlled, crossover study to assess its effectiveness against renal itch. METHODS: We enrolled in the trial 25 adult patients on haemodialysis who were asked to daily record the severity of their pruritus on a visual analogue scale. The patients were randomly assigned to receive gabapentin for 4 weeks followed by placebo for 4 weeks or the reverse sequence. Gabapentin or placebo were administered thrice weekly, at the end of haemodialysis sessions. RESULTS: The mean pruritus score of the cohort before the study was 8.4 +/- 0.94. After placebo intake, it decreased to 7.6 +/- 2.6 (P = 0.098). The score of four patients decreased by >50% following placebo. After gabapentin administration, the mean score decreased significantly, to 1.2 +/- 1.8 (P = 0.0001), although one patient's symptoms did not improve significantly. No patient dropped out of the study due to adverse effects from gabapentin. CONCLUSIONS: Our study shows that gabapentin is safe and effective for treating uraemic pruritus in haemodialysis patients. Our results also support the neuropathic hypothesis of uraemic pruritus.

Amines↗
PubMed2002

The interaction between gabapentin and amitriptyline in the rat formalin test after systemic administration.

UNLABELLED: We examined the effects of systemically administered gabapentin on flinching and biting/licking behaviors produced by 2.5% formalin in the rat, compared these with those of amitriptyline, and determined the effects of combinations of gabapentin with amitriptyline. Gabapentin produced a dose-related inhibition of Phase 2, but not Phase 1, flinching and biting/licking behaviors. In contrast, amitriptyline produced an increase in Phase 2 flinching behaviors while simultaneously decreasing biting/licking behaviors. Fifty percent effective dose (ED50) values against biting/licking behaviors were 22.9 +/- 1.3 mg/kg and 8.5 +/- 1.3 mg/kg for gabapentin and amitriptyline, respectively. Combinations of increasing fractional increments of ED50 doses of gabapentin and amitriptyline produced an additive effect against biting/licking behaviors, as revealed by isobolographic analysis. These increments had no effect on flinching behaviors except at the ED25 + ED25 doses, at which flinching was increased, again revealing additivity between the two drugs. Flinching behaviors in rats do not reflect the analgesic properties of systemically administered amitriptyline observed in humans and may not be useful for predicting an effect of combinations of drugs with amitriptyline. Biting/licking behaviors do reflect analgesic properties for both drugs and may be more useful in this regard. IMPLICATIONS: By use of the rat formalin test, a model of persistent pain, we examined the effect of a combination of amitriptyline and gabapentin, which are used to treat chronic pain in humans. The drug combination produced additive analgesia against one outcome, but another outcome was more ambiguous.

Acetates↗
PubMed2002

A randomized study of the effects of single-dose gabapentin versus placebo on postoperative pain and morphine consumption after mastectomy.

BACKGROUND: The anticonvulsant gabapentin has proven effective for neuropathic pain in three large placebo-controlled clinical trials. Experimental and clinical studies have demonstrated antihyperalgesic effects in models involving central neuronal sensitization. It has been suggested that central neuronal sensitization may play an important role in postoperative pain. The aim of the study was to investigate the effect of gabapentin on morphine consumption and postoperative pain in patients undergoing radical mastectomy. METHODS: In a randomized, double-blind, placebo-controlled study, 70 patients received a single dose of oral gabapentin (1,200 mg) or placebo 1 h before surgery. Patients received patient-controlled analgesia with morphine at doses of 2.5 mg with a lock-out time of 10 min for 4 h postoperatively. Pain was assessed on a visual analog scale at rest and during movement, and side effects were assessed on a four-point verbal scale 2 and 4 h postoperatively. RESULTS: Thirty-one patients in the gabapentin group and 34 patients in the placebo group completed the study. Gabapentin reduced total morphine consumption from a median of 29 (interquartile range, 21-33) to 15 (10-19) mg (P< 0.0001). Pain during movement was reduced from 41 (31-59) to 22 (10-38) mm at 2 h postoperatively (P < 0.0001) and from 31 (12-40) to 9 (3-34) mm at 4 h postoperatively (P = 0.018). No significant differences between groups were observed with regard to pain at rest or side effects. CONCLUSION: A single dose of 1,200 mg oral gabapentin resulted in a substantial reduction in postoperative morphine consumption and movement-related pain after radical mastectomy, without significant side effects. These promising results should be validated in other acute pain models involving central neuronal sensitization.

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PubMed2006

A randomized study of the effects of gabapentin on postamputation pain.

BACKGROUND: Pain after amputation is common but difficult to treat. Therefore, the authors examined whether postoperative treatment with gabapentin could reduce postamputation stump and phantom pain. METHODS: Forty-six patients scheduled to undergo lower limb amputation were randomly assigned to receive oral gabapentin or placebo. Treatment was started on the first postoperative day and continued for 30 days. The daily dose of gabapentin or placebo was gradually increased to 2,400 mg/day. The intensity of stump and phantom pain was recorded every day on a numeric rating scale (0-10) during the 30-day treatment period. Five interviews were performed after 7, 14, and 30 days and after 3 and 6 months. RESULTS: Results from 41 patients were included in the data analysis. The risk of phantom pain (gabapentin vs. placebo) was 55.0% versus 52.6% (risk difference, 2.4%; 95% confidence interval, -28.9 to 33.7%; P = 0.88; 30 days) and 58.8% versus 50.0% (risk difference, 8.8%; 95% confidence interval, -23.3 to 40.9%; P = 0.59; 6 months). The median intensity of phantom pain (gabapentin vs. placebo) was 1.5 (range, 0-9.0) versus 1.2 (range, 0-6.6) (P = 0.60; 30 days) and 1.0 (range, 0-6.0) versus 0.5 (range, 0-5.0) (P = 0.77; 6 months). The median intensity of stump pain was 0.85 (range, 0-8.2) versus 1.0 (range, 0-5.4) (P = 0.68; 30 days) and 0 (range, 0-8.0) versus 0 (range, 0-5.0) (P = 0.58; 6 months). CONCLUSION: Gabapentin administered in the first 30 postoperative days after amputation does not reduce the incidence or intensity of postamputation pain.

Aged↗
PubMed1997

The effect of gabapentin on neuropathic pain.

OBJECTIVE: To evaluate the effects of gabapentin on pain scores and opiate use. DESIGN: Retrospective review of patients charts who received gabapentin for at least 30 days. Data were collected concerning patients' diagnosis, current drug use, concurrent drug use, gabapentin dose, pain scores, and patient-reported side effects. Patients were divided into three groups based on their pain diagnosis; low back, neuropathic, and myofascial pain. The neuropathic group was subdivided into postherpetic neuralgia, diabetic neuropathy, sympathetically maintained pain, and phantom pain. SETTING: Two tertiary referral teaching hospitals in southeastern Michigan. RESULTS: A total of 122 charts were reviewed and included in this study. A significant decrease in pain scores with gabapentin was seen in the neuropathic pain group (paired t-test, p < .0001) but not in the low back pain group. Of the neuropathic pain group, patients with postherpetic neuralgia had the greatest decrease in pain scores. Ten patients showed a > 75% decrease in pain scores, of these: nine had a direct nerve injury, and one had postherpetic neuralgia. Opiate use was unchanged in all groups. Patients who were taking opiates had significantly less benefit with gabapentin use in terms of pain score. Patient-reported side effects were similar to those reported in a nonchronic pain population. CONCLUSION: Gabapentin may be a useful adjunct for treating neuropathic pain with a minimum of side effects. Particular advantage may be gained with the use of this drug for postherpetic neuralgia and direct peripheral nerve injuries.

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PubMed1998

Gabapentin does not alter single-dose lithium pharmacokinetics.

Lithium (Li) and gabapentin are both exclusively eliminated by renal excretion. When used in combination, a competitive drug-drug interaction could possibly alter Li renal excretion with important clinical implications considering the rather narrow therapeutic index of Li. This study examined the single-dose pharmacokinetic profiles of Li in 13 patients receiving placebo and then steady-state gabapentin (mean daily dose: 3,646.15 mg). During both phases, a single 600-mg dose of Li was orally administered with serial Li levels obtained at time zero and at 0.25, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, and 72 hours. The pharmacokinetic parameters assessed were the following: area under the concentration time curve (AUC) for Li, maximal concentration of Li (Li Cmax), and time to reach peak Li concentration (Li Tmax). For patients receiving gabapentin, the mean Li AUC at 72 hours was 9.91+/-3.54 mmol x hr/mL and did not differ significantly from the mean Li AUC of 10.19+/-2.89 mmol x hr/mL for patients receiving placebo. The mean Li Cmax was 0.69+/-0.13 mmol/L for gabapentin patients and did not differ from the mean Li Cmax of 0.72+/-0.15 mmol/L for placebo patients. The mean serum Li Tmax was 1.38+/-0.62 hours for gabapentin patients and did not differ significantly from the mean serum Li Tmax of 1.5+/-0.91 hours for placebo patients. These data indicate that gabapentin treatment at this high therapeutic dose does not cause clinically significant alterations in short-term Li pharmacokinetics in patients with normal renal function. These preliminary data warrant further controlled study in a larger, more heterogenous patient sample and a longer duration of assessment, but they do suggest that these two medications may be administered in combination for the management of bipolar disorder.

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PubMed1999

Treatment of social phobia with gabapentin: a placebo-controlled study.

A randomized, double-blind, placebo-controlled, parallel-group study was conducted to evaluate the efficacy and safety of gabapentin in relieving the symptoms of social phobia. Sixty-nine patients were randomly assigned to receive double-blind treatment with either gabapentin (dosed flexibly between 900 and 3,600 mg daily in three divided doses) or placebo for 14 weeks. A significant reduction (p < 0.05) in the symptoms of social phobia was observed among patients on gabapentin compared with those on placebo as evaluated by clinician- and patient-rated scales. Results were similar for the intent-to-treat and week-2 completer populations. Adverse events were consistent with the known side effect profile of gabapentin. Dizziness (p = 0.05), dry mouth (p = 0.05), somnolence, nausea, flatulence, and decreased libido occurred at a higher frequency among patients receiving gabapentin than among those receiving placebo. No serious adverse events or deaths were reported. On the basis of these limited data, it seems that gabapentin offers a favorable risk-benefit ratio for the treatment of patients with social phobia. Further studies are required to confirm this effect and to determine whether a dose-response relationship exists.

Acetates↗
PubMed2000

The anticonvulsant compound gabapentin possesses anxiolytic but not amnesic effects in rats.

This report describes the effects of the antiepileptic agent gabapentin on anxiety and memory. Male Wistar rats received intraperitoneal administrations of gabapentin (10, 30 and 100mg/kg), diazepam (1 mg/kg), saline or diazepam vehicle 30 minutes prior to experimental procedures. Animals were: (1) tested on step-down inhibitory avoidance (footshock 0.3 mA) and habituation to an open-field for memory assessment; and (2) submitted to the elevated plus-maze to evaluate the potential anxiolytic effects of gabapentin. Animals treated with gabapentin showed a reduction in anxiety similar to that observed in animals treated with diazepam. Memory was not affected by gabapentin in any of the tests, but was impaired by diazepam. The lack of effects of gabapentin on memory suggest a potential advantage of this drug over compounds with previously known anxiolytic property, which have amnesic effects at doses used for the treatment of anxiety disorders.

Acetates↗
PubMed2005

Effect of preemptive gabapentin on postoperative pain relief and morphine consumption following lumbar laminectomy and discectomy: a randomized, double-blinded, placebo-controlled study.

Synergism between gabapentin and morphine in treating incisional pain has been demonstrated in animal experiments and clinical studies. The efficacy of gabapentin for treatment of perioperative pain remains controversial. This study was designed to detect the influence of gabapentin premedication on morphine consumption in the immediate postoperative period in patients undergoing lumbar laminectomy and discectomy. Either gabapentin 800 mg (in two equally divided doses) or placebo was given preoperatively to 60 adult patients undergoing elective lumbar laminectomy or discectomy in a double-blinded, placebo-controlled, randomized study. Standard general anesthesia was given to all the patients. Morphine was administered via patient-controlled analgesia pump in the immediate postoperative period for first 8 hours. Pain at rest and on movement was assessed using a Verbal Rating Scale (VRS) every 2 hours for the first 8 postoperative hours. There were no differences in demographics or surgical duration between the two groups. The amount of fentanyl administered in the intraoperative period was similar between the two groups. In the postoperative period, the VRS score for pain at 0, 2, 4, 6, and 8 hours was not significantly different between the two groups. Highest median VRS score was recorded at 0 hours postoperatively in both groups (VRS: rest = 6, movement = 8 in placebo group; rest = 6, movement = 8 in gabapentin group). Total morphine consumption and side effects were similar in the two groups. Gabapentin does not decrease the morphine requirement or morphine side effects in the immediate postoperative period following lumbar laminectomy and discectomy.

Adolescent↗
PubMed2005

Presynaptic NMDA autoreceptors facilitate axon excitability: a new molecular target for the anticonvulsant gabapentin.

Gabapentin is a drug with anticonvulsant and analgesic properties causing the reduction of neurotransmitter release. We show that one of the mechanisms implicated in this effect of gabapentin is the reduction of the axon excitability measured as an amplitude change of the presynaptic fibre volley (FV) in the CA1 area of rat hippocampal slices. Interestingly, we found that gabapentin-induced depression of FV is mimicked and occluded by NMDA receptor (NMDA-R) antagonists, indicating that these receptors are located presynaptically and are activated by ambient levels of glutamate. Conversely, NMDA application (20 microM, 10 min) elicits a reversible FV potentiation which is reduced by gabapentin. Both NMDA- and gabapentin-induced FV changes are partially explained by modifications in the firing threshold of individual fibres. Increasing [K(+)](o) does not mimic or occlude (at a concentration of 6.5 mM) the effect of NMDA on FV amplitude, which makes it unlikely that a rise in [K(+)](o) induced by NMDA receptor activation could indirectly participate in the potentiation of the FV. The NMDA-induced FV potentiation is independent of extracellular calcium presence but is completely inhibited in a low-Na(+) solution (50% reduction) or under NMDA channel block (high Mg(2+) or MK 801). These findings suggest that sodium entry through presynaptic NMDA-R channels facilitates axon excitability. The interaction of gabapentin with this newly described mechanism might contribute to its therapeutic benefits.

Amines↗