Intrathecal neuropeptide Y exacerbates nerve injury-induced mechanical hyperalgesia

In normal animals, spinal administration of neuropeptide Y induces analgesia to thermal stimuli, but has no effect on mechanical thresholds. Recent anatomical studies, however, have shown that following nerve injury there is an altered expression of neuropeptide Y and its receptors. The aim of this behavioural study, therefore, is to examine the effect of intrathecal administration of neuropeptide Y its agonists and an antagonist on mechanical nociceptive thresholds in rats with partial injury to the sciatic nerve. Test agents were administered for 14 days 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 mechanical threshold as compared to the sham operated, contralateral paw. The nerve injury-induced hyperalgesia is exacerbated by 2 mu M neuropeptide Y and by 2 mu M [Leu(31),Pro(34)]-neuropeptide Y, a Y-1 receptor agonist. The Y-2 receptor agonist, N-acetyl-[Leu(28),Leu(31)]-neuropeptide Y24-36 (2 mu M), had no effect on the nerve injury-induced hyperalgesia. The putative neuropeptide Y antagonist, alpha-trinositol (10 mu M), significantly attenuated the nerve injury-induced hyperalgesia. This study suggests that neuropeptide Y may contribute to nerve injury-induced mechanical hyperalgesia via the Y-1 receptor and provides further insight into the possible mechanisms underlying nerve injury-induced hyperalgesia to mechanical stimuli.