The Neurological Safety of Epidural Gabapentin in Rats: A Light Microscopic Examination

Gabapentin acts primarily on the central nervous system. Therefore, we hypothesized that the direct epidural administration of gabapentin could have various advantages over its oral administration with respect to required dose, side effects, and efficacy. However, before administering gabapentin into the epidural space in a clinical setting, its neurotoxicity must be examined in animals. Thus, we evaluated neurotoxicity of epidural gabapentin by observing behavioral and sensory-motor changes, and by histopathological examinations of spinal cords and dorsal root ganglia in the rat. Twenty-seven rats were randomly divided into 3 groups, which were administered 0.3 mL (30 mg) of epidural gabapentin (group G, n = 9) and the same volume of epidural alcohol (group A, n = 9) or normal saline (group N, n = 9). No rats in groups G and N showed sensory-motor dysfunction, behavioral change, or histopathological abnormalities over a 3-wk observation period, whereas all rats in group A showed abnormalities. We conclude that the direct epidural injection of gabapentin in rats did not show any neurotoxic evidence in terms of sensory-motor functions and behavior, or by a microscopic histopathological evaluation. This study represents a first promising step toward the trial of epidural gabapentin in a clinical setting.

[1]  M. Maltoni,et al.  Gabapentin for neuropathic cancer pain: a randomized controlled trial from the Gabapentin Cancer Pain Study Group. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  H. Ugurlu,et al.  Gabapentin Is a First Line Drug for the Treatment of Neuropathic Pain in Spinal Cord Injury , 2004, Spine.

[3]  M. Bennett,et al.  Gabapentin in the treatment of neuropathic pain , 2004, Palliative medicine.

[4]  Yong-Chul Kim,et al.  The Neurotoxicity of Epidural Hyaluronic Acid in Rabbits: A Light and Electron Microscopic Examination , 2003, Anesthesia and analgesia.

[5]  N. Calcutt,et al.  Injury Type-Specific Calcium Channel α2δ-1 Subunit Up-Regulation in Rat Neuropathic Pain Models Correlates with Antiallodynic Effects of Gabapentin , 2002, Journal of Pharmacology and Experimental Therapeutics.

[6]  D. Choi,et al.  The effect of intrathecal gabapentin on mechanical and thermal hyperalgesia in neuropathic rats induced by spinal nerve ligation. , 2002, Journal of Korean medical science.

[7]  R. Pinnock,et al.  Expression of voltage-gated calcium channel subunits in rat dorsal root ganglion neurons , 2001, Neuroscience Letters.

[8]  N. Klugbauer,et al.  Calcium Channel α2δ Subunits—Structure and Gabapentin Binding , 2001 .

[9]  T. Yaksh,et al.  The effect of intrathecal gabapentin on pain behavior and hemodynamics on the formalin test in the rat. , 1999, Anesthesia and analgesia.

[10]  Y. C. Kim,et al.  Spreading pattern of epidurally administered contrast medium in rabbits , 1998, Acta anaesthesiologica Scandinavica.

[11]  F. Bajrović,et al.  Extent of Nociceptive Dermatomes in Adult Rats Is Not Primarily Maintained by Axonal Competition , 1998, Experimental Neurology.

[12]  T. Yaksh,et al.  The Effect of Intrathecal Gabapentin and 3-Isobutyl gamma-Aminobutyric Acid on the Hyperalgesia Observed After Thermal Injury in the Rat , 1998, Anesthesia and analgesia.

[13]  J. Eisenach,et al.  Studies on the Safety of Glucose and Paraben-Containing Neostigmine for Intrathecal Administration , 1997, Anesthesia and analgesia.

[14]  K. Elliott,et al.  Spinal gabapentin is antinociceptive in the rat formalin test , 1997, Neuroscience Letters.

[15]  Z. Bosnjak,et al.  Mechanism of Mesenteric Venodilatation after Epidural Lidocaine in Rabbits , 1994, Anesthesiology.

[16]  R. Traub,et al.  Immunohistochemical and Quantitative Demonstrations of Pain Induced by Lumbar Nerve Root Irritation of the Rat , 1994, Spine.

[17]  V. Bille-Hansen,et al.  Chronic catheterization of the epidural space in rabbits: a model for behavioural and histopathological studies. Examination of meptazinol neurotoxicity , 1993, Acta anaesthesiologica Scandinavica.

[18]  J. Mussini,et al.  Is Ketamine or Its Preservative Responsible for Neurotoxicity in the Rabbit? , 1993, Anesthesiology.

[19]  C. Post,et al.  Repeated intrathecal injections of dezocine produce antinociception without evidence for neurotoxicity in the rat: a study of morphometric evaluation of spinal cord histology. , 1992, Anesthesia and analgesia.

[20]  D. Eimerl,et al.  Epidural capsaicin produces prolonged segmental analgesia in the rat , 1987, Experimental Neurology.

[21]  F. Zdrahal,et al.  [Intrathecal alcohol neurolysis of the lower sacral roots in inoperable rectal cancer]. , 1985, Der Anaesthesist.

[22]  R. C. Singler Alcohol neurolysis of sciatic and femoral nerves. , 1981, Anesthesia and analgesia.

[23]  J. Eledjam,et al.  [Chemical neurolysis using alcohol (alcoholization) in the treatment of spasticity in the hemiplegic]. , 1993, Cahiers d'anesthesiologie.

[24]  J. Pélissier,et al.  Neurolyse chimique à l'alcool (alcoolisation) dans le traitement de la spasticité chez l'hémiplégique. , 1993 .

[25]  T. Yaksh,et al.  Studies in animals should precede human use of spinally administered drugs. , 1989, Anesthesiology.

[26]  V. Chan,et al.  An algorithm for the treatment of pain in advanced cancer. , 1989, The Hospice journal.