INTRATHECAL NEUROPEPTIDE-Y EXACERBATES NERVE INJURY-INDUCED MECHANICAL HYPERALGESIA

In normal animals, spinal administration of neuropeptide Y induces ana lgesia to thermal stimuli, but has no effect on mechanical thresholds. Recent anatomical studies, however, have shown that following nerve i njury there is an altered expression of neuropeptide Y and its recepto rs. The aim of this behavioural study, therefore, is to examine the ef fect of intrathecal administration of neuropeptide Y its agonists and an antagonist on mechanical nociceptive thresholds in rats with partia l injury to the sciatic nerve. Test agents were administered for 14 da ys via osmotic pumps (0.5 mu l/day) attached to intrathecal catheters and the nociceptive flexion reflex was quantified using an Ugo Basile Analgesymeter. Partial injury to the sciatic nerve, in animals treated intrathecally with saline, induces a significant decrease in mechanic al threshold as compared to the sham operated, contralateral paw. The nerve injury-induced hyperalgesia is exacerbated by 2 mu M neuropeptid e Y and by 2 mu M [Leu(31),Pro(34)]-neuropeptide Y, a Y-1 receptor ago nist. The Y-2 receptor agonist, N-acetyl-[Leu(28),Leu(31)]-neuropeptid e Y24-36 (2 mu M), had no effect on the nerve injury-induced hyperalge sia. The putative neuropeptide Y antagonist, alpha-trinositol (10 mu M ), significantly attenuated the nerve injury-induced hyperalgesia. Thi s study suggests that neuropeptide Y may contribute to nerve injury-in duced mechanical hyperalgesia via the Y-1 receptor and provides furthe r insight into the possible mechanisms underlying nerve injury-induced hyperalgesia to mechanical stimuli.