Presynaptic glutamatergic transmission and feedback system of oxytocinergic neurons in the hypothalamus of a rat model of adjuvant arthritis. (July 2020)

• Record Type: Journal Article
• Authors: Fujitani, Teruaki; Matsuura, Takanori; Kawasaki, Makoto; Suzuki, Hitoshi; Nishimura, Haruki; Baba, Kazuhiko; Yamanaka, Yoshiaki; Ohnishi, Hideo; Ueta, Yoichi; Sakai, Akinori
• Is Part Of: Molecular pain. Volume 16(2020)
• Publication Date: 2020-07
• Subjects: Chronic inflammation -- glutamate -- feedback system -- oxytocin -- L-368, 899 -- Nω-Nitro-L-arginine methyl ester hydrochloride -- nitric oxide synthase -- hypothalamic paraventricular nucleus -- transgenic rat -- whole-cell patch-clamp; Pain -- Molecular aspects -- Periodicals; Pain -- Pathophysiology -- Periodicals; Pain -- Physiological aspects -- Periodicals; 616.0472
• DOI: 10.1177/1744806920943334
• Languages: English
• ISSNs: 1744-8069

Abstract

The neurohypophysial hormone oxytocin (OXT) is synthesized in the hypothalamic paraventricular and supraoptic nuclei. Recently, some studies have considered OXT to be important in sensory modulation and that the OXT protein is upregulated by acute and chronic nociception. However, the mechanism by which OXT is upregulated in neurons is unknown. In this study, we examined the resting membrane potentials and excitatory postsynaptic currents in OXT-ergic neurons in the paraventricular nucleus in adjuvant arthritis rat model, a model of chronic inflammation, using whole-cell patch-clamping. Transgenic rats expressing OXT and monomeric red fluorescent protein 1 (mRFP1) fusion protein to visualize the OXT-ergic neurons were used, and the OXT-mRFP1 transgenic rat model of adjuvant arthritis was developed by injection of heat-killed Mycobacterium butyricum . Furthermore, the feedback system of synthesized OXT was also examined using the OXT receptor antagonist L-368, 899. We found that the resting membrane potentials and frequency of miniature excitatory postsynaptic currents and spontaneous excitatory postsynaptic currents in OXT-monomeric red fluorescent protein 1 neurons in the paraventricular nucleus were significantly increased in adjuvant arthritis rats. Furthermore, L-368, 899 dose-dependently increased the frequency of miniature excitatory postsynaptic currents and spontaneous excitatory postsynaptic currents in OXT-ergic neurons. Following bath application of the GABAA receptor antagonist picrotoxin and the cannabinoid receptor 1 antagonist AM 251, L-368, 899 still increased the frequency of miniature excitatory postsynaptic currents. However, following bath application of the nitric oxide synthase inhibitor Nω-Nitro-L-arginine methyl ester hydrochloride, L-368, 899 did not alter the miniature excitatory postsynaptic current frequency. Thus, it is suggested that OXT-ergic neuron activity is upregulated via an increase in glutamate release, and that the upregulated OXT neurons have a feedback system with released endogenous OXT. It is possible that nitric oxide, but not GABA, may contribute to the feedback system of OXT neurons in chronic inflammation.