Gabapentin reverses the allodynia produced by the administration of anti-GD2 ganglioside, an immunotherapeutic drug.
Systemically administered, the anti-GD2 antibody produces allodynia demonstrated by decreased mechanical withdrawal threshold. Electrophysiologic recordings indicate a probable neuropathic origin, as small-diameter sensory fibers develop continuous high-frequency discharge after antibody administration. Gabapentin (GBP) is a gamma-aminobutyric acid analog originally synthesized for its anticonvulsant actions. Several open-label clinical studies, as well as a wealth of anecdotal evidence, suggest that GBP may be beneficial for the treatment of neuropathic pain. This study examined the effects of GBP given as a posttreatment after induction of an anti-GD2-associated allodynia. Anti-GD2 (1 mg/kg intravenously [i.v.]) administered to Sprague-Dawley rats reduced the mean withdrawal threshold from 14.71 to 4.95 g (P < 0.001), as measured by using von Frey hairs. This was reversed by GBP in a dose-dependent fashion; the minimal effective dose was between 3 and 30 mg/kg i.v. The maximal percent analgesic effect of GBP was 76% and 93% at doses of 30 and 100 mg/kg, respectively (P < 0.001). With these doses, side effects were minimal and were manifested as slightly decreased spontaneous movement and startle response. No changes were seen in reflex responses to corneal or pinna stimulation, and no motor deficits were observed. These data support the use of GBP as an effective therapy for neuropathic pain.


CONCLUSIONS
After the administration of anti-GD2 antibody, rats display an escape reaction to light touch, increased blood pressure, and aberrant firing in nerve fibers associated with pain transmission. Systemic gabapentin reduced or eliminated the escape response and reversed the hypertension with minimal side effects. This suggests that gabapentin blocked the antibody-associated (neuropathic) pain.
Gillin
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Department of Anesthesiology, University of California-San Diego, La Jolla 92093-0818, USA.
Sorkin
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LS
D000085:Acetates / Q000494:pharmacology*; D000588:Amines; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D001794:Blood Pressure / Q000187:drug effects; D003509:Cyclohexanecarboxylic Acids; D004305:Dose-Response Relationship, Drug; D000077206:Gabapentin; D005732:Gangliosides / Q000276:immunology*; D008297:Male; D010146:Pain / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D012694:Serine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D000700:Analgesics; D000911:Antibodies, Monoclonal; D003509:Cyclohexanecarboxylic Acids; D005732:Gangliosides; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; D005680:gamma-Aminobutyric Acid; C019403:ganglioside, GD2; D000077206:Gabapentin