THE EFFECTS OF MEXILETINE, DESIPRAMINE AND FLUOXETINE IN RAT MODELS INVOLVING CENTRAL SENSITIZATION

Drugs that are clinically effective (mexiletine and desipramine) or in effective (fluoxetine) in the treatment of human neuropathic pain were evaluated for efficacy in rat models involving central sensitization (i.e., formalin model and the L5/L6 spinal nerve ligation model of neu ropathic pain) using tests that differ in stimulus modality: noxious c hemical stimulus (formalin model) as well as noxious (pin prick) and i nnocuous mechanical stimuli (application of von Frey filaments). Mexil etine (10-100 mg/kg, s.c.) significantly (P < 0.05) attenuated hyperal gesia in formalin-treated (60 mg/kg and 100 mg/kg) and neuropathic rat s (100 mg/kg) as well as tactile allodynia in neuropathic rats (100 mg /kg). Desipramine (1-100 mg/kg, s.c.), on the other hand, reduced hype ralgesia significantly (P < 0.05) in formalin-treated (3, 10, 30 and 1 00 mg/kg) and neuropathic rats (10 mg/kg and 100 mg/kg), but did not r educe tactile allodynia in the neuropathic rats. Fluoxetine (3-30 mg/k g, s.c.) did not inhibit either hyperalgesia or allodynia in any of th e tests employed. Fluoxetine, which is relatively ineffective in reduc ing neuropathic pain in humans, was also ineffective in reducing hyper algesia and allodynia associated with central sensitization in rats. T hus, drugs which are effective in reducing human neuropathic pain cons istently attenuated hyperalgesia in formalin-treated or neuropathic ra ts. Desipramine also distinguished mechanical hyperalgesia from tactil e allodynia in rats rendered neuropathic by spinal nerve ligation. The se data are consistent with the hypothesis that the neuronal mechanism s underlying these two manifestations of neuropathic pain are differen t.