PMID- 29128909 OWN - NLM STAT- MEDLINE DCOM- 20190422 LR - 20190422 IS - 1438-8359 (Electronic) IS - 0913-8668 (Linking) VI - 32 IP - 1 DP - 2018 Feb TI - Central noradrenergic activity affects analgesic effect of Neuropeptide S. PG - 48-53 LID - 10.1007/s00540-017-2427-y [doi] AB - BACKGROUND: 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). METHODS: A total 66 male Sprague-Dawley rats weighing 350-450 g 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 10.0 nmol), tail-flick NPS alone icv (0.0 and 10.0 nmol), and hot-plate with NPS and DSP-4 (0 or 50 mg/kg ip). In hot-plate with NPS and DSP-4 group, noradrenaline content in the cerebral cortex, pons, hypothalamus, were measured. RESULTS: NPS 10 nmol icv prolonged hot plate (%MPE) but not tail flick latency at 30 and 40 min after administration. DSP-4 50 mg/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 10 nmol 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. CONCLUSIONS: NPS analgesia interacts with LC noradrenergic neuronal activity. FAU - Jinushi, Kei AU - Jinushi K AD - Department of Anesthesiology, Hirosaki University Hospital, Hirosaki, 036-8563, Japan. FAU - Kushikata, Tetsuya AU - Kushikata T AUID- ORCID: 0000-0003-4263-0177 AD - Department of Anesthesiology, Hirosaki University Graduate School of Medicine, Zaifu 5, Hirosaki, 036-8562, Japan. tetsuyak@hirosaki-u.ac.jp. FAU - Kudo, Takashi AU - Kudo T AD - Department of Anesthesiology, Hirosaki University Hospital, Hirosaki, 036-8563, Japan. FAU - Calo, Girolamo AU - Calo G AD - Section of Pharmacology, Department of Medical Science, National Institute of Neuroscience, University of Ferrara, Ferrara, Italy. FAU - Guerrini, Remo AU - Guerrini R AD - Department of Chemical and Pharmaceutical Sciences, LTTA, University of Ferrara, 44121, Ferrara, Italy. FAU - Hirota, Kazuyoshi AU - Hirota K AD - Department of Anesthesiology, Hirosaki University Graduate School of Medicine, Zaifu 5, Hirosaki, 036-8562, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20171111 PL - Japan TA - J Anesth JT - Journal of anesthesia JID - 8905667 RN - 0 (Analgesics) RN - 0 (Benzylamines) RN - PQ1P7JP5C1 (DSP 4) RN - X4W3ENH1CV (Norepinephrine) SB - IM MH - Analgesics/*pharmacology MH - Animals MH - Benzylamines/*pharmacology MH - Brain/metabolism MH - Hypothalamus/metabolism MH - Locus Coeruleus/metabolism MH - Male MH - Neurons/metabolism MH - Norepinephrine/*metabolism MH - Pain/*drug therapy MH - Pain Measurement MH - Rats MH - Rats, Sprague-Dawley OTO - NOTNLM OT - Analgesia OT - Central noradrenergic neuron OT - DSP-4 OT - Hotplate OT - Neuropeptide S EDAT- 2017/11/13 06:00 MHDA- 2019/04/23 06:00 CRDT- 2017/11/13 06:00 PHST- 2017/04/06 00:00 [received] PHST- 2017/11/02 00:00 [accepted] PHST- 2017/11/13 06:00 [pubmed] PHST- 2019/04/23 06:00 [medline] PHST- 2017/11/13 06:00 [entrez] AID - 10.1007/s00540-017-2427-y [pii] AID - 10.1007/s00540-017-2427-y [doi] PST - ppublish SO - J Anesth. 2018 Feb;32(1):48-53. doi: 10.1007/s00540-017-2427-y. Epub 2017 Nov 11.