Involvement of 5-HT1A receptors of the thalamic descending pathway in the analgesic effect of intramuscular heating-needle stimulation in a rat model of lumbar disc herniation

Yuhong Ma; Yijun Zhan; Jian Pei; Gang Ye; Yaoxin Chen; Wenyan Zhu; Haiyue Shen

doi:10.3389/fnins.2023.1222286

Involvement of 5-HT_1A receptors of the thalamic descending pathway in the analgesic effect of intramuscular heating-needle stimulation in a rat model of lumbar disc herniation

Front Neurosci. 2023 Jul 18:17:1222286. doi: 10.3389/fnins.2023.1222286. eCollection 2023.

Authors

Yuhong Ma^#^{1

2}, Yijun Zhan^#¹, Jian Pei¹, Gang Ye³, Yaoxin Chen¹, Wenyan Zhu¹, Haiyue Shen¹

Affiliations

¹ Department of Acupuncture, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
² Department of Acupuncture and Traumatology, Shanghai Baoshan Luodian Hospital, Shanghai, China.
³ Department of Rehabilitation Medicine, Tongji Hospital Affiliated to Tongji University, Shanghai, China.

^# Contributed equally.

Abstract

Background: Intramuscular (IM) heating-needle therapy, a non-painful thermal therapy, has been found to exert an analgesic effect via the thalamic ventromedial (VM) nucleus, solely by reducing the triggering threshold for descending inhibition; this could be modulated by intracephalic 5-hydroxytryptamine-1A (5-HT_1A) receptors, rather than via the regular analgesia pathway. In this study, the effect and the potential serotonergic mechanism of IM heating-needle stimulation at 43°C were explored in the case of the pathological state of lumbar disc herniation (LDH).

Methods: A modified classic rat model of LDH, induced via autologous nucleus pulposus implantation, was utilized. IM inner heating-needles were applied at the attachment point of skeletal muscle on both sides of the L4 and L5 spinous processes. WAY-100635 and 8-OH-DAPT, 5-HT_1A receptor antagonist and agonist, were separately injected into the bilateral thalamic mediodorsal (MD) and VM nucleus via an intrathalamic catheter. Nociception was assessed by bilateral paw withdrawal reflexes elicited by noxious mechanical and heat stimulation.

Results: IM heating-needle stimulation at a temperature of 43°C for 30 or 45 min significantly relieved both mechanical and heat hyperalgesia in the rat model of LDH (P < 0.05). Heat hyperalgesia was found to be significantly enhanced by administration of WAY-100635 into the thalamic VM nucleus, blocking the effect of heating-needle stimulation in a dose-dependent manner (P < 0.05), while no effects were detected after injection into the thalamic MD nucleus (P > 0.05). Injection of 8-OH-DAPT into the thalamic MD nucleus exerted no modulating effects on either mechanical or heat hyperalgesia (P > 0.05).

Conclusion: IM heating-needle stimulation at 43°C for 30 min may activate 5-HT_1A mechanisms, via the thalamic VM nucleus, to attenuate hyperalgesia in a rat model of LDH. This innocuous form of thermal stimulation is speculated to selectively activate the descending inhibition mediated by the thalamic VM nucleus, exerting an analgesic effect, without the involvement of descending facilitation of the thalamic MD nucleus.

Keywords: 5-HT1A receptor; descending modulation; intramuscular heating-needle stimulation; lumbar disc herniation; thalamic ventromedial nucleus.

Grants and funding

This work was supported by the Key Scientific Research Program of the Science and Technology Commission of Shanghai Municipality (22Y11922900 and 18401970500), the TCM genre program of Shanghai Municipal Health Bureau [ZY (2021-2023)-0209-10], and the Science and Technology Innovation Project of Longhua Hospital (YD202218).