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 microliter/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 microM neuropeptide Y and by 2 microM [Leu31,Pro34]-neuropeptide Y, a Y1 receptor agonist. The Y2 receptor agonist, N-acetyl-[Leu28,Leu31]-neuropeptide Y24-36 (2 microM), had no effect on the nerve injury-induced hyperalgesia. The putative neuropeptide Y antagonist, alpha-trinositol (10 microM), significantly attenuated the nerve injury-induced hyperalgesia. This study suggests that neuropeptide Y may contribute to nerve injury-induced mechanical hyperalgesia via the Y1 receptor and provides further insight into the possible mechanisms underlying nerve injury-induced hyperalgesia to mechanical stimuli.
White
D M
DM
Department of Anaesthesia and Pain Management, University of Sydney, N.S.W., Australia.
D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology; D007839:Functional Laterality; D006930:Hyperalgesia / Q000503:physiopathology*; D007278:Injections, Spinal; D007295:Inositol Phosphates / Q000008:administration & dosage / Q000494:pharmacology; D009478:Neuropeptide Y / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D010146:Pain / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000037:antagonists & inhibitors; D012584:Sciatic Nerve / Q000293:injuries* / Q000502:physiology*; D012684:Sensory Thresholds / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007295:Inositol Phosphates; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C059368:atrinositol