Endogenous oxytocin exerts anti-nociceptive and anti-inflammatory effects in rats

Haruki Nishimura, Mitsuhiro Yoshimura, Makiko Shimizu, Kenya Sanada, Satomi Sonoda, Kazuaki Nishimura, Kazuhiko Baba, Naofumi Ikeda, Yasuhito Motojima, Takashi Maruyama, Yuki Nonaka, Ryoko Baba, Tatsushi Onaka, Takafumi Horishita, Hiroyuki Morimoto, Yasuhiro Yoshida, Makoto Kawasaki, Akinori Sakai, Masafumi Muratani, Becky Conway-CampbellStafford Lightman, Yoichi Ueta

Research output: Contribution to journalArticle (Academic Journal)peer-review

20 Citations (Scopus)

Abstract

Oxytocin is involved in pain transmission, although the detailed mechanism is not fully understood. Here, we generate a transgenic rat line that expresses human muscarinic acetylcholine receptors (hM3Dq) and mCherry in oxytocin neurons. We report that clozapine-N-oxide (CNO) treatment of our oxytocin-hM3Dq-mCherry rats exclusively activates oxytocin neurons within the supraoptic and paraventricular nuclei, leading to activation of neurons in the locus coeruleus (LC) and dorsal raphe nucleus (DR), and differential gene expression in GABA-ergic neurons in the L5 spinal dorsal horn. Hyperalgesia, which is robustly exacerbated in experimental pain models, is significantly attenuated after CNO injection. The analgesic effects of CNO are ablated by co-treatment with oxytocin receptor antagonist. Endogenous oxytocin also exerts anti-inflammatory effects via activation of the hypothalamus-pituitary-adrenal axis. Moreover, inhibition of mast cell degranulation is found to be involved in the response. Taken together, our results suggest that oxytocin may exert anti-nociceptive and anti-inflammatory effects via both neuronal and humoral pathways.

Original languageEnglish
Pages (from-to)907
JournalCommunications Biology
Volume5
Issue number1
DOIs
Publication statusPublished - 5 Sept 2022

Bibliographical note

© 2022. The Author(s).

Keywords

  • Analgesics/metabolism
  • Animals
  • Anti-Inflammatory Agents/metabolism
  • GABAergic Neurons/metabolism
  • Oxytocin/metabolism
  • Pain/drug therapy
  • Paraventricular Hypothalamic Nucleus/metabolism
  • Rats
  • Rats, Transgenic

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