Analgesic effect of intrathecal desipramine on carrageenan-induced thermal hyperalgesia in the rat.

Abstract

We examined if intrathecal desipramine, a selective norepinephrine reuptake inhibitor, would modulate peripheral inflammation-induced hyperalgesia. Rats were chronically implanted with a lumbar intrathecal catheter and paw withdrawal latency (PWL) to noxious heat stimuli was assessed. Unilateral hindpaw inflammation was induced by intraplantar carrageenan injection. Carrageenan injection significantly (P < 0.05) reduced PWL of the injected paw (from 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 desipramine 10, 30, 60 and 100 micrograms, which did not produce analgesic effects in untreated rats, dose-dependently reversed the shortened PWL on the ipsilateral 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 yohimbine 10 micrograms did not antagonize the anti-hyperalgesic effects of desipramine (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 hyperalgesia is unlikely to be inhibition of norepinephrine reuptake within the spinal cord.