Peripheral Beta-2 Adrenergic Receptors Mediate the Sympathetic Efferent Activation from Central Nervous System to Splenocytes in a Mouse Model of Fibromyalgia

Yamashita, Shiori; Dozono, Naoki; Tobori, Shota; Nagayasu, Kazuki; Kaneko, Shuji; Shirakawa, Hisashi; Ueda, Hiroshi

doi:10.3390/ijms24043465

Open AccessArticle

Peripheral Beta-2 Adrenergic Receptors Mediate the Sympathetic Efferent Activation from Central Nervous System to Splenocytes in a Mouse Model of Fibromyalgia

by

Shiori Yamashita

^1,†

,

Naoki Dozono

^1,2,†,

Shota Tobori

¹

,

Kazuki Nagayasu

¹

,

Shuji Kaneko

¹,

Hisashi Shirakawa

^1,*

and

Hiroshi Ueda

^1,2,3,*

¹

Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan

²

Department of Pharmacology and Therapeutic Innovation, Nagasaki University Institute of Biomedical Sciences, Nagasaki 852-8521, Japan

³

Graduate Institute of Pharmacology, National Defense Medical Center, Nei-hu, Taipei 114201, Taiwan

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2023, 24(4), 3465; https://doi.org/10.3390/ijms24043465

Submission received: 24 November 2022 / Revised: 30 January 2023 / Accepted: 6 February 2023 / Published: 9 February 2023

(This article belongs to the Special Issue Novel Mechanisms and Drug Molecules Modulating Chronic Pain)

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Abstract

Abnormalities in the peripheral immune system are involved in the pathophysiology of fibromyalgia, although their contribution to the painful symptoms remains unknown. Our previous study reported the ability of splenocytes to develop pain-like behavior and an association between the central nervous system (CNS) and splenocytes. Since the spleen is directly innervated by sympathetic nerves, this study aimed to examine whether adrenergic receptors are necessary for pain development or maintenance using an acid saline-induced generalized pain (AcGP) model (an experimental model of fibromyalgia) and whether the activation of these receptors is also essential for pain reproduction by the adoptive transfer of AcGP splenocytes. The administration of selective β2-blockers, including one with only peripheral action, prevented the development but did not reverse the maintenance of pain-like behavior in acid saline-treated C57BL/6J mice. Neither a selective α1-blocker nor an anticholinergic drug affects the development of pain-like behavior. Furthermore, β2-blockade in donor AcGP mice eliminated pain reproduction in recipient mice injected with AcGP splenocytes. These results suggest that peripheral β2-adrenergic receptors play an important role in the efferent pathway from the CNS to splenocytes in pain development.

Keywords: fibromyalgia; adrenergic receptors; central nervous system; AcGP model; splenocytes; sympathetic efferent; pain development

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MDPI and ACS Style

Yamashita, S.; Dozono, N.; Tobori, S.; Nagayasu, K.; Kaneko, S.; Shirakawa, H.; Ueda, H. Peripheral Beta-2 Adrenergic Receptors Mediate the Sympathetic Efferent Activation from Central Nervous System to Splenocytes in a Mouse Model of Fibromyalgia. Int. J. Mol. Sci. 2023, 24, 3465. https://doi.org/10.3390/ijms24043465

AMA Style

Yamashita S, Dozono N, Tobori S, Nagayasu K, Kaneko S, Shirakawa H, Ueda H. Peripheral Beta-2 Adrenergic Receptors Mediate the Sympathetic Efferent Activation from Central Nervous System to Splenocytes in a Mouse Model of Fibromyalgia. International Journal of Molecular Sciences. 2023; 24(4):3465. https://doi.org/10.3390/ijms24043465

Chicago/Turabian Style

Yamashita, Shiori, Naoki Dozono, Shota Tobori, Kazuki Nagayasu, Shuji Kaneko, Hisashi Shirakawa, and Hiroshi Ueda. 2023. "Peripheral Beta-2 Adrenergic Receptors Mediate the Sympathetic Efferent Activation from Central Nervous System to Splenocytes in a Mouse Model of Fibromyalgia" International Journal of Molecular Sciences 24, no. 4: 3465. https://doi.org/10.3390/ijms24043465

APA Style

Yamashita, S., Dozono, N., Tobori, S., Nagayasu, K., Kaneko, S., Shirakawa, H., & Ueda, H. (2023). Peripheral Beta-2 Adrenergic Receptors Mediate the Sympathetic Efferent Activation from Central Nervous System to Splenocytes in a Mouse Model of Fibromyalgia. International Journal of Molecular Sciences, 24(4), 3465. https://doi.org/10.3390/ijms24043465

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Peripheral Beta-2 Adrenergic Receptors Mediate the Sympathetic Efferent Activation from Central Nervous System to Splenocytes in a Mouse Model of Fibromyalgia

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