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Central noradrenergic activity affects analgesic effect of Neuropeptide S

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Abstract

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.

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Acknowledgements

This study was supported by grants-in-aid for scientific research (23592242, 24659690, 25462394 and 26462327) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and Grant for Hirosaki University Institutional Research.

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Authors and Affiliations

  1. Department of Anesthesiology, Hirosaki University Hospital, Hirosaki, 036-8563, Japan

    Kei Jinushi & Takashi Kudo

  2. Department of Anesthesiology, Hirosaki University Graduate School of Medicine, Zaifu 5, Hirosaki, 036-8562, Japan

    Tetsuya Kushikata & Kazuyoshi Hirota

  3. Section of Pharmacology, Department of Medical Science, National Institute of Neuroscience, University of Ferrara, Ferrara, Italy

    Girolamo Calo

  4. Department of Chemical and Pharmaceutical Sciences, LTTA, University of Ferrara, 44121, Ferrara, Italy

    Remo Guerrini

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  1. Kei Jinushi
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Contributions

KJ performed data collection, data analysis and prepare the manuscript. KJ approved the final manuscript. KJ attests to the integrity of the original data and the analysis reported in this manuscript. TeK conducted of the study, performed data collection, and prepared the manuscript. TeK approved the final manuscript. TeK attests to the integrity of the original data and the analysis reported in this manuscript. TeK is the archival author. TaK helped design the study and performed data collection, data analysis. TaK approved the final manuscript. GC helped design the study and prepare the manuscript. GC approved the final manuscript. RG helped design the study and prepared the synthesis of Neuropeptide S. RG approved the final manuscript. KH performed data analysis and prepared the manuscript. KH approved the final manuscript.

Corresponding author

Correspondence to Tetsuya Kushikata.

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Conflict of interest

Kei Jinushi: None. Tetsuya Kushikata: Grants-in-Aid for surveillance of academic research activity in Japan from Japan Society for the Promotion of Science Nos. 23592242, 24659690, 25462394 and 26462327. Takashi Kudo: None. Girolamo Calo: None. Remo Guerrini: None. Kazuyoshi Hirota: Grants-in-Aid for surveillance of academic research activity in Japan from Japan Society for the Promotion of Science No. 24659690.

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Jinushi, K., Kushikata, T., Kudo, T. et al. Central noradrenergic activity affects analgesic effect of Neuropeptide S. J Anesth 32, 48–53 (2018). https://doi.org/10.1007/s00540-017-2427-y

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  • DOI: https://doi.org/10.1007/s00540-017-2427-y

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