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在腰椎间盘突出症大鼠模型中,丘脑下行通路5-羟色胺受体参与肌肉内热针刺激的镇痛作用。

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

作者信息

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

机构信息

Department of Acupuncture, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Department of Acupuncture and Traumatology, Shanghai Baoshan Luodian Hospital, Shanghai, China.

出版信息

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

DOI:10.3389/fnins.2023.1222286
PMID:37534035
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10390831/
Abstract

BACKGROUND

Intramuscular (IM) heating-needle therapy, a non-painful thermal therapy, has been found to exert an analgesic effect 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) 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 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 ( < 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 ( < 0.05), while no effects were detected after injection into the thalamic MD nucleus ( > 0.05). Injection of 8-OH-DAPT into the thalamic MD nucleus exerted no modulating effects on either mechanical or heat hyperalgesia ( > 0.05).

CONCLUSION

IM heating-needle stimulation at 43°C for 30 min may activate 5-HT 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.

摘要

背景

肌内加热针疗法是一种无痛热疗法,已发现其仅通过降低下行抑制的触发阈值,就能在丘脑腹内侧(VM)核发挥镇痛作用;这可能是由脑内5-羟色胺-1A(5-HT)受体调节的,而非通过常规镇痛途径。在本研究中,探讨了在腰椎间盘突出症(LDH)病理状态下,43℃肌内加热针刺激的效果及潜在的血清素能机制。

方法

采用经自体髓核植入诱导的改良经典大鼠LDH模型。在L4和L5棘突两侧的骨骼肌附着点处应用肌内内热针。5-HT受体拮抗剂WAY-100635和激动剂8-OH-DAPT通过丘脑内导管分别注入双侧丘脑背内侧(MD)核和VM核。通过有害机械和热刺激引发的双侧爪退缩反射评估伤害感受。

结果

在大鼠LDH模型中,43℃的肌内加热针刺激30或45分钟可显著减轻机械性和热痛觉过敏(P<0.05)。发现向丘脑VM核注射WAY-100635可显著增强热痛觉过敏,以剂量依赖方式阻断加热针刺激的效果(P<0.05),而注入丘脑MD核后未检测到效果(P>0.05)。向丘脑MD核注射8-OH-DAPT对机械性或热痛觉过敏均无调节作用(P>0.05)。

结论

43℃的肌内加热针刺激30分钟可能通过丘脑VM核激活5-HT机制,以减轻大鼠LDH模型中的痛觉过敏。推测这种无害的热刺激形式可选择性激活由丘脑VM核介导的下行抑制,发挥镇痛作用,而不涉及丘脑MD核的下行易化作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/206f/10390831/a93263e30fff/fnins-17-1222286-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/206f/10390831/eb812eab8bda/fnins-17-1222286-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/206f/10390831/de78b0584998/fnins-17-1222286-g0002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/206f/10390831/cd0c5a50d82d/fnins-17-1222286-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/206f/10390831/ec906954f805/fnins-17-1222286-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/206f/10390831/a93263e30fff/fnins-17-1222286-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/206f/10390831/eb812eab8bda/fnins-17-1222286-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/206f/10390831/de78b0584998/fnins-17-1222286-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/206f/10390831/69b0371824f2/fnins-17-1222286-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/206f/10390831/cd0c5a50d82d/fnins-17-1222286-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/206f/10390831/ec906954f805/fnins-17-1222286-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/206f/10390831/a93263e30fff/fnins-17-1222286-g0006.jpg

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