SYSTEMIC GABAPENTIN AND S(-3-ISOBUTYL-GAMMA-AMINOBUTYRIC ACID BLOCK SECONDARY HYPERALGESIA())

Gabapentin (GBP) and S(+)-3-isobutyl-gamma-aminobutyric acid (IBG) are anticonvulsant agents which are effective against many clinical and e xperimental neuropathic pain states. We examined the efficacy of these agents in a new rat model of secondary mechanical hyperalgesia genera ted by a mild thermal injury. Under brief halothane anesthesia, an inj ury was induced by applying one heel to a hot surface (52.5 degrees C) for 45 s. GBP, IBG or saline was injected i.p, just prior to the inju ry. Mean mechanical withdrawal threshold (MWT) was determined using vo n Frey hairs before and at 30 min intervals for 3 h following the inju ry. MWT outside the injury area decreased post-injury (secondary hyper algesia, allodynia), but primary (site of injury) mechanical hyperalge sia was not observed. Secondary hyperalgesia exhibited a tendency towa rd recovery over time. Time to onset of the anti-allodynic effect of G BP was 30-60 min. The minimum effective GBP dose was 100 mg/kg; 300 mg /kg GBP totally inhibited the drop in MWT, but was accompanied by pron ounced sedation. Anti-allodynic effects of IBG were apparent at the fi rst post-injury measure of MWT (30 min). Thirty milligrams per kilogra m was the minimum effective dose; 100 mg/kg IBG totally blocked the al lodynia with minimal side effects. Our findings demonstrate a dose-dep endent blockade of the mechanical sensitivity caused by a mild thermal injury by both GBP and IBG. Results indicate that IBG is more effecti ve than GBP in this model at doses which do not cause sedation. These observations support the suggested use of these or related gamma-amino acid analogues as an effective treatment for post-operative pain. (C) 1998 Elsevier Science B.V. All rights reserved.