Central noradrenergic activity affects analgesic effect of Neuropeptide S.

Abstract

Neuropeptide S (NPS) is an endogenous neuropeptide controlling anxiolysis, wakefulness, and analgesia. NPS containing neurons exist near to the locus coeruleus (LC) involved in the descending anti-nociceptive system. NPS interacts with central noradrenergic neurons; thus brain noradrenergic signaling may be involved in NPS-induced analgesia. We tested NPS analgesia in noradrenergic neuron-lesioned rats using a selective LC noradrenergic neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4). A total 66 male Sprague-Dawley rats weighing 350-450g were used. Analgesic effects of NPS were evaluated using hot-plate and tail-flick test with or without DSP-4. The animal allocated into 3 groups; hot-plate with NPS alone intracerebroventricular (icv) (0.0, 1.0, 3.3, and 10.0nmol), tail-flick NPS alone icv (0.0 and 10.0nmol), and hot-plate with NPS and DSP-4 (0 or 50mg/kg ip). In hot-plate with NPS and DSP-4 group, noradrenaline content in the cerebral cortex, pons, hypothalamus, were measured. NPS 10nmol icv prolonged hot plate (%MPE) but not tail flick latency at 30 and 40min after administration. DSP-4 50mg/kg decreased noradrenaline content in the all 3 regions. The NA depletion inhibited NPS analgesic effect in the hot plate test but not tail flick test. There was a significant correlation between hot plate latency (percentage of maximum possible effect: %MPE) with NPS 10nmol and NA content in the cerebral cortex (p=0.017, r 2=0.346) which noradrenergic innervation arisen mainly from the LC. No other regions had the correlation. NPS analgesia interacts with LC noradrenergic neuronal activity.