Stretch-induced nerve injury: a proposed technique for the study of nerve regeneration and evaluation of the influence of gabapentin on this model

The rat models currently employed for studies of nerve regeneration present distinct disadvantages. We propose a new technique of stretch-induced nerve injury, used here to evaluate the influence of gabapentin (GBP) on nerve regeneration. Male Wistar rats (300 g; n=36) underwent surgery and exposure of the median nerve in the right forelimbs, either with or without nerve injury. The technique was performed using distal and proximal clamps separated by a distance of 2 cm and a sliding distance of 3 mm. The nerve was compressed and stretched for 5 s until the bands of Fontana disappeared. The animals were evaluated in relation to functional, biochemical and histological parameters. Stretching of the median nerve led to complete loss of motor function up to 12 days after the lesion (P<0.001), compared to non-injured nerves, as assessed in the grasping test. Grasping force in the nerve-injured animals did not return to control values up to 30 days after surgery (P<0.05). Nerve injury also caused an increase in the time of sensory recovery, as well as in the electrical and mechanical stimulation tests. Treatment of the animals with GBP promoted an improvement in the morphometric analysis of median nerve cross-sections compared with the operated vehicle group, as observed in the area of myelinated fibers or connective tissue (P<0.001), in the density of myelinated fibers/mm2 (P<0.05) and in the degeneration fragments (P<0.01). Stretch-induced nerve injury seems to be a simple and relevant model for evaluating nerve regeneration.

Uremic pruritus in hemodialysis patients: treatment with desloratidine versus gabapentin

INTRODUCTION: Uremic pruritus is common among dialysis patients. Effective treatments are not readily available. Early evidence with antihistamines and gabapentin indicate variable effects. OBJECTIVE: To compare the efficacy and side effects of gabapentin and desloratadine in patients with dialysis pruritus. METHODS: Prospective, open-label, cross-over clinical trial in 22 patients on chronic hemodialysis with sustained pruritus over a period of at least 60 days. After a one-week run-in period, we assigned patients to three weeks of either gabapentin 300 mg thrice weekly or desloratadine 5 mg thrice weekly. After a one-week washout period, each patient crossed-over to the alternate regimen for three more weeks. The primary endpoint of the study was the change in the visual analogue pruritus score (VAS). RESULTS: Nineteen subjects completed the two treatment blocks and were available for analysis. VAS scores decreased with both treatments (5.95 to 4.6 with gabapentin, p = 0.07; 5.89 to 3.4 with desloratadine, p = 0.004), but only desloratadine reached statistical significance. There were no differences when comparing the final pruritus score with gabapentin and desloratadine (4.6 versus 3.4, p = 0.16) Excessive sedation was common with gabapentin. Desloratadine was well tolerated. CONCLUSION: Desloratadine provides significant relief of uremic pruritus compared with no therapy. gabapentin has marginal efficacy. Desloratadine is better tolerated than gabapentin.

Única dosis de gabapentin preoperatorio para analgesia postoperatoria: revisión de literatura

Introducción: el dolor postoperatorio supone un reto para todo anestesiólogo, en los últimos años se ha propuesto el Gabapentin preoperatorio como una buena opción paraanalgesia postoperatoria sin efectos secundarios. Metodología: se realizó una revisión sistemática incluyendo ensayos clínicos controlados realizados en pacientes adultos sometidos a diferentes tipos de cirugía. Se hizo una búsqueda en las bases de datos (PUBMED, EMBASE, LILACS, SCIELO), utilizando los términos “gabapentin”, “postoperative pain”, se extrajeron datos con los estudios incluidos. Resultados: se encontraron un total de 155 artículos, 16 de ellos cumplieron criterios de inclusión. Todos fueron evidencia tipo Ib. Las dosis utilizadas de gabapentin estuvieron entre 300 mg y 1200 mg y el intervalo de administración se encontró entre dos y una hora antes de cirugía, Hay una diferencia estadísticamente significativa en el manejo del dolor con el uso de Gabapentin preoperatorio (p<0,01) comparado contra placebo evaluado en el postoperatorio inmediato, a las 12 horas y 24 horas; así como tendencia a menor uso de opioides y menor náusea y vómito postoperatorio, Discusión: los resultados concuerdan con otros estudios similares realizados previamente y soportan el efecto del Gabapentin como analgésico directo y no solo como coadyuvante del manejo del dolor. Aún falta determinar cuál es la dosis más efectiva, aunque hasta la fecha el gabapentin supone menos efectos adversos, igualmente falta determinar si el efecto de menor nausea y vomito postoperatorio se relaciona con un efecto directo del gabapentin o por ahorro en consumo de opioides.Metodología Se realizó una revisión sistemática incluyendo ensayos clínicos controlados realizados en pacientes adultos sometidos a diferentes tipos de cirugía. Se hizo una búsqueda en las bases de datos (PUBMED, EMBASE, LILACS, SCIELO), utilizando los términos “gabapentin”, “postoperative pain”, se extrajeron datos con los estudios incluidos. ResultadosSe encontraron un total de 155 artículos, 16 de ellos cumplieron criterios de inclusión. Todos fueron evidencia tipo Ib. Las dosis utilizadas de gabapentin estuvieron entre 300 mg y 1200 mg y el intervalo de administración se encontró entre dos y una hora antes de cirugía, Hay una diferencia estadísticamente significativa en el manejo del dolor con el uso de Gabapentin preoperatorio (p<0,01) comparado contra placebo evaluado en el postoperatorio inmediato, a las 12 horas y 24 horas; así como tendencia a menor uso de opioides y menor náusea y vómito postoperatorio, DiscusiónLos resultados concuerdan con otros estudios similares realizados previamente y soportan el efecto del Gabapentin como analgésico directo y no solo como coadyuvante del manejo del dolor. Aún falta determinar cual es la dosis más efectiva, aunque hasta la fecha el gabapentin supone menos efectos adversos, igualmente falta determinar si el efecto de menor nausea y vomito postoperatorio se relaciona con un efecto directo del gabapentin o por ahorro en consumo de opioides.

The effect of intrathecal gabapentin on neuropathic pain is independent of the integrity of the dorsolateral funiculus in rats

Aim: This study evaluates the contribution of inhibitory pain pathways that descend to the spinal cord through the dorsolateral funiculus (DLF) on the effect of intrathecal gabapentin against spinal nerve ligation (SNL)-induced behavioral hypersensitivity to mechanical stimulation in rats. Main method: Rats were submitted to a sham or complete ligation of the right LS and L6 spinal nerves and a sham or complete DLF lesion. Next, the changes induced by intrathecal administration of gabapentin on the paw withdrawal threshold of rats to mechanical stimulation were evaluated electronically. Key findings: Intrathecal gabapentin (200 mu g/5 mu l) that was injected 2 or 7 days after surgery fully inhibited the SNL-induced behavioral hypersensitivity to mechanical stimulation in sham DLF-Iesioned rats; gabapentin was effective against the SNL-induced behavioral hypersensitivity to mechanical stimulation also in DLF-Iesioned rats. Significance: The effect of intrathecally administered gabapentin against SNL-induced behavioral hypersensitivity to mechanical stimulation in rats does not depend on the activation of nerve fibers that descend to the spinal cord via the DLF. (C) 2012 Elsevier Inc. All rights reserved.

Low single dose gabapentin does not affect prefrontal and occipital gamma-aminobutyric acid concentrations

The γ-aminobutyric acid (GABA) system has been proposed as a target for novel antidepressant and anxiolytic treatments. Emerging evidence suggests that gabapentin (GBP), an anticonvulsant drug that significantly increases brain GABA levels, is effective in the treatment of anxiety disorders. The current study was designed to measure prefrontal and occipital GABA levels in medication-free healthy subjects after taking 0 mg, 150 mg and 300 mg GBP. Subjects were scanned on a 3T scanner using a transmit-receive head coil that provided a relatively homogenous radiofrequency field to obtain spectroscopy measurement in the medial prefrontal (MPFC) and occipital cortex (OCC). There was no dose-dependent effect of GBP on GABA levels in the OCC or MPFC. There was also no effect on Glx, choline or N-acetyl-aspartate concentrations. The previously reported finding of increased GABA levels after GBP treatment is not evident for healthy subjects at the dose of 150 and 300 mg. As a result, if subjects are scanned on a 3T scanner, low dose GPB is not useful as an experimental challenge agent on the GABA system.

Pregabalin - learning from gabapentin?

The author overviews the use of pregabalin in neuropathic pain. (non-author abstract)

Gabapentin treatment for bipolar disorders

OBJECTIVE: To review the effectiveness data on the use of gabapentin in bipolar disorders. DATA SOURCES: Clinical literature was accessed through MEDLINE (January 1985–November 2000). Key search terms included gabapentin, mood stabilizer, and bipolar disorder. DATA SYNTHESIS: Bipolar disorder is a complex condition that can be difficult to treat effectively. Mood stabilizers are increasingly being used to manage bipolar disorder. Studies that used gabapentin in bipolar disorders are evaluated. CONCLUSIONS: From the data presented, gabapentin cannot be recommended for treatment of bipolar disorder. Further studies are required to determine whether gabapentin has any role in the management of bipolar disorder.

Analgesic synergism of gabapentin and carbamazepine in rat model of diabetic neuropathic pain

Purpose: To evaluate synergy in the analgesic effects of a combination therapy of carbamazepine (CBZ) and gabapentin (GBP) in diabetic neuropathic pain. Methods: Neuropathic pain was produced in rats by a single intraperitoneal injection of streptozotocin (STZ) at 60 mg/kg. CBZ, GBP, and their combination were orally administered at varying doses (GBP 30 - 180 mg/kg; CBZ 20 - 40 mg/kg) comparable to their therapeutic doses in humans. Nociceptive responses in the diabetic rats were assessed using hot plate test. Results: Hot plate latency significantly increased with oral administration of GBP at a dose of 180 mg/kg when compared with control group (p < 0.05), while at a dose of 90 mg/kg, the increase was not significant. Oral administration of CBZ at doses of 20 and 40 mg/kg did not produce any significant impact on hot plate latency. However, a combination of GBP at 90 mg/kg and CBZ at 20 mg/kg produced significant increase in latency, compared with control group and other groups (p < 0.05), except the group that received 180 mg/kg GBP. The combination of low dose GBP 30 mg/kg and carbamazepine 30 mg/kg had no significant effect on latency (p > 0.05). Conclusion: The results obtained in this study provide useful information on the combination therapy of GBP and CBZ, which may be applied in the treatment of pain in diabetic neuropathy.

Signal Transduction, Plasma Membrane Calcium Movements, and Pigment Translocation in Freshwater Shrimp Chromatophores

Crustacean color change results from the differential translocation of chromatophore pigments, regulated by neurosecretory peptides like red pigment concentrating hormone (RPCH) that, in the red ovarian chromatophores of the freshwater shrimp Macrobrachium olfersi, triggers pigment aggregation via increased cytosolic cGMP and Ca(2+) of both smooth endoplasmatic reticulum (SER) and extracellular origin. However, Ca(2+) movements during RPCH signaling and the mechanisms that regulate intracellular [Ca(2+)] are enigmatic. We investigate Ca(2+) transporters in the chromatophore plasma membrane and Ca(2+) movements that occur during RPCH signal transduction. Inhibition of the plasma membrane Ca(2+)-ATPase by La(3+) and indirect inhibition of the Na(+)/Ca(2+) exchanger by ouabain induce pigment aggregation, revealing a role for both in Ca(2+) extrusion. Ca(2+) channel blockade by La(3+) or Cd(2+) strongly inhibits slow-phase RPCH-triggered aggregation during which pigments disperse spontaneously. L-type Ca(2+) channel blockade by gabapentin markedly reduces rapid-phase translocation velocity; N- or P/Q-type blockade by omega-conotoxin MVIIC strongly inhibits RPCH-triggered aggregation and reduces velocity, effects revealing RPCH-signaled influx of extracellular Ca(2+). Plasma membrane depolarization, induced by increasing external K(+) from 5 to 50 mM, produces Ca(2+)-dependent pigment aggregation, whereas removal of K(+) from the perfusate causes pigment hyperdispersion, disclosing a clear correlation between membrane depolarization and pigment aggregation; K(+) channel blockade by Ba(2+) also partially inhibits RPCH action. We suggest that, during RPCH signal transduction, Ca(2+) released from the SER, together with K(+) channel closure, causes chromatophore membrane depolarization, leading to the opening of predominantly N- and/or P/Q-type voltage-gated Ca(2+) channels, and a Ca(2+)/cGMP cascade, resulting in pigment aggregation. J. Exp. Zool. 313A:605-617, 2010. (C) 2010 Wiley-Liss, Inc.