TY - JOUR
T1 - Endogenous oxytocin exerts anti-nociceptive and anti-inflammatory effects in rats
AU - Nishimura, Haruki
AU - Yoshimura, Mitsuhiro
AU - Shimizu, Makiko
AU - Sanada, Kenya
AU - Sonoda, Satomi
AU - Nishimura, Kazuaki
AU - Baba, Kazuhiko
AU - Ikeda, Naofumi
AU - Motojima, Yasuhito
AU - Maruyama, Takashi
AU - Nonaka, Yuki
AU - Baba, Ryoko
AU - Onaka, Tatsushi
AU - Horishita, Takafumi
AU - Morimoto, Hiroyuki
AU - Yoshida, Yasuhiro
AU - Kawasaki, Makoto
AU - Sakai, Akinori
AU - Muratani, Masafumi
AU - Conway-Campbell, Becky
AU - Lightman, Stafford
AU - Ueta, Yoichi
N1 - © 2022. The Author(s).
PY - 2022/9/5
Y1 - 2022/9/5
N2 - 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.
AB - 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.
KW - Analgesics/metabolism
KW - Animals
KW - Anti-Inflammatory Agents/metabolism
KW - GABAergic Neurons/metabolism
KW - Oxytocin/metabolism
KW - Pain/drug therapy
KW - Paraventricular Hypothalamic Nucleus/metabolism
KW - Rats
KW - Rats, Transgenic
U2 - 10.1038/s42003-022-03879-8
DO - 10.1038/s42003-022-03879-8
M3 - Article (Academic Journal)
C2 - 36064593
SN - 2399-3642
VL - 5
SP - 907
JO - Communications Biology
JF - Communications Biology
IS - 1
ER -