GABAPENTIN REVERSES THE ALLODYNIA PRODUCED BY THE ADMINISTRATION OF ANTI-GD2 GANGLIOSIDE, AN IMMUNOTHERAPEUTIC DRUG

Systemically administered, the anti-GD, antibody produces allodynia de monstrated by decreased mechanical withdrawal threshold. Electrophysio logic recordings indicate a probable neuropathic origin, as small-diam eter 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 evidenc e, 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/k g intravenously [IV]) administered to Sprague-Dawley rats reduced the mean withdrawal threshold from 14.71 to 4.95 g (P < 0.001), as measure d by using von Frey hairs. This was reversed by GBP in a dose-dependen t fashion; the minimal effective dose was between 3 and 30 mg/kg IV. T he 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 ef fects were minimal and were manifested as slightly decreased spontaneo us movement and startle response. No changes were seen in reflex respo nses to corneal or pinna stimulation and no motor deficits were observ ed. These data support the use of GBP as an effective therapy for neur opathic pain. Implications: After the administration of anti-GD2 antib ody, rats display an escape reaction to light touch, increased blood p ressure, and aberrant firing in nerve fibers associated with pain tran smission. Systemic gabapentin reduced or eliminated the escape respons e and reversed the hypertension with minimal side effects. This sugges ts that gabapentin blocked the antibody-associated (neuropathic) pain.