Analgesic effect of intrathecal desipramine on carrageenan-induced thermalhyperalgesia in the rat

We examined if intrathecal desipramine, a selective norepinephrine reuptake inhibitor, would modulate peripheral inflammation-induced hyperalgesia. Ra ts were chronically implanted with a lumbar intrathecal catheter and paw wi thdrawal latency (PWL) to noxious heat stimuli was assessed. Unilateral hin dpaw inflammation was induced by intraplantar carrageenan injection. Carrag eenan injection significantly (P<0.05) reduced PWL of the injected paw (fro m mean 11.4 (SEM 0.6) s to 3.5 (0.2) s, 3 h after carrageenan), but not of the contralateral side (from 11.6 (0.2) s to 11.2 (0.5) s). Intrathecal des ipramine 10, 30, 60 and 100 mu g, which did not produce analgesic effects i n untreated rats, dose-dependently reversed the shortened PWL on the ipsila teral side (3.3 (0.2), 5.3 (0.4), 6.2 (0.3) and 9.6 (0.2) s, respectively) without affecting the contralateral side. Pretreatment with intrathecal yoh imbine 10 mu g did not antagonize the anti-hyperalgesic effects of desipram ine (from 9.6 (0.2) to 9.8 (0.3) s). Our results suggest that the mechanism underlying the analgesic effect of desipramine on inflammation-induced hyp eralgesia is unlikely to be inhibition of norepinephrine reuptake within th e spinal cord.