综述与专论: 非药物疗法在慢性疼痛干预中的应用和治疗机制
作者:
作者单位:

1)宁波大学医学部,浙江省病理生理学技术研究重点实验室,宁波 315211;2)宁波大学附属第一医院,宁波 315000;3)宁波市鄞州区第二医院麻醉科,宁波 315100

作者简介:

黄长顺 Tel: 13957882779, E-mail: fyyhuangchangshun@nbu.edu.cn陈晓薇 Tel: 0574-87609594, E-mail: chenxiaowei@nbu.edu.cnHUANG Chang-Shun. Tel: 86-13957882779, E-mail: fyyhuangchangshun@nbu.edu.cnCHEN Xiao-Wei. Tel: 86-574-87609594, E-mail: chenxiaowei@nbu.edu.cn

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基金项目:

国家自然科学基金(82071239,81671089),浙江省自然科学基 金(LY22H090003),浙江省医药卫生科技项目(2023KY1059) 和 宁波市自然科学基金(2019A610284,2022J070) 资助。


Review: Application and Therapeutic Mechanisms of Non-pharmacological Interventions in The Management of Chronic Pain
Author:
Affiliation:

1)Zhejiang Key Laboratory of Pathophysiology, Health Science Center, Ningbo University, Ningbo 315211, China;2)The First Affiliated Hospital of Ningbo University, Ningbo 315000, China;3)Department of Anesthesiology, the Second Hospital of Yinzhou District, Ningbo 315100, China

Fund Project:

This work was supported by grants from The National Natural Science Foundation of China (82071239, 81671089), The Zhejiang Natural Science Foundation of China (LY22H090003), The Zhejiang Medical and Health Technology Project (2023KY1059), and The Ningbo Natural Science Foundation Project (2019A610284, 2022J070).

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    摘要:

    疼痛是一种由身体组织的真实或潜在损伤引起的不舒服感觉,慢性疼痛为持续时间超过3个月以上的疼痛。慢性疼痛可以由多种疾病引起,发病率高。然而应用药物治疗慢性疼痛存在一定的局限性。非阿片类药物对部分类型的慢性痛,如神经病理性疼痛,疗效不佳。而阿片类镇痛药物则因成瘾和易诱发胃肠道副作用而受限,因此非药物干预治疗逐渐受到关注。目前临床上对于治疗慢性疼痛常用的非药物疗法包括脉冲射频(pulsed radiofrequency,PRF)、脊髓电刺激(spinal cord stimulation,SCS)、光生物调节(photobiomodulation,PBM)和重复经颅磁刺激(repetitive transcranial magnetic stimulation,rTMS)。最新研究揭示了光照和声音的中枢镇痛机制,提示光疗和声疗在临床转化上的潜力。鉴于光照和声音都属于非侵入性治疗,因此这两者在临床应用上具有广阔的前景。本文通过梳理以上非药物镇痛手段的干预方法、优缺点以及镇痛机制,希望为深入理解慢性痛的发病机制提供依据,为优化疼痛的非药物干预手段提供新的思路。

    Abstract:

    Pain is an unpleasant sensory and experience associated with, or resembling that associated with, actual emotional or potential tissue damage. Chronic pain is pain that persists for more than 3 months. Chronic pain is caused by a variety of conditions with high incidence. However, the use of medication to treat chronic pain has certain limitations. Non-opioid medications have limited efficacy for some types of chronic pain, such as neuropathic pain. However, opioid analgesics have limitations due to addiction and gastrointestinal side effects, so non-drug intervention therapy has gradually gained attention. Currently, common non-pharmacological interventions for chronic pain include pulsed radiofrequency (PRF), spinal cord stimulation (SCS), photobiomodulation (PBM) and repetitive transcranial magnetic stimulation (rTMS). PRF is a technique using a low temperature and pulse of electromagnetic radiation to disrupt nerve signaling without denaturing the fibers. PRF therapy involves the insertion of a radiofrequency needle around the target nerve under computer tomography (CT) guidance. The RF generator emits a pulsed current to the needle tip, forming a magnetic field near the target nerve tissue and exerting a neuromodulatory role. Compared with traditional thermocoagulation, the temperature of PRF does not exceed 42°C and finally exerts an analgesic effect without damaging the nerve. Recent studies reveal that analgesic mechanisms of PRF involve downregulations of functions of voltage-gated sodium and calcium channels and ionotropic purinergic receptors (Nav1.7, Cav2.2, and P2X3), reduction of the releases of neuropeptides (calcitonin gene-related peptide (CGRP) and substance P (SP)), neurotransmitters (glutamate) and pro-inflammatory mediators (interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), and suppression of intracellular signal pathways (ERK/MAPK and p38MAPK). SCS modulates the releases and functions of neurotransmitters by downregulating excitatory glutamate systems and upregulating inhibitory gamma-aminobutyric acid (GABA), endogenous opioids, and the endocannabinoid system. SCS is a therapeutic method that effectively alleviates chronic pain by electrically stimulating the spinal nerves. This procedure involves the implantation of electrodes into the epidural space under local anesthesia, with precise targeting of specific segments of the spinal cord. By delivering pulsed electrical currents, the spinal nerves can be selectively stimulated, effectively blocking the transmission of pain signals and providing much-needed relief from chronic pain. SCS suppresses neuroinflammation, including downregulating glial activation, decreasing releases of pro-inflammatory mediators (colony stimulating factor-1 (CSF-1), resolvin D1 (RVD1), TNF-α and IL-1β), and regulating p38MAPK signal pathways. SCS also increases the expression levels of lysosome-associated membrane protein 2 (Lamp2) and mature cathepsin D (matu-CTSD) to restore lysosome function and promote autophagosome degradation. Light therapies utilize specific wavelengths of light to alleviate pain and promote healing. Light therapies use different types of light sources, including visible light, infrared, and ultraviolet rays. Recent advances in light therapies on chronic pain reveal that green light irradiation enhances morphine analgesic effect, mainly by increasing beta-endorphin and enkephalin levels in rats, reducing postsynaptic glutamate receptor expression and inhibiting microglia activation. A recent study using sound to mitigate pain and reports the mechanism of sound-mediated analgesic occurs through the cortical-thalamic circuitry. The study highlights that the analgesic effect of sound is solely dependent on the intensity of the sound, regardless of its nature or characteristics. In conclusion, the analgesic mechanisms of non-pharmacological interventions suggest their potential in the clinic. This article reviews the intervention methods, advantages, disadvantages and analgesic mechanisms of the above non-pharmacological interventions. The review will help to better understand the pathogenesis of chronic pain and to optimize non-pharmacological interventions for chronic pain.

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林相宏,江仁,黄长顺,陈晓薇.综述与专论: 非药物疗法在慢性疼痛干预中的应用和治疗机制[J].生物化学与生物物理进展,2023,50(10):2406-2419

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历史
  • 收稿日期:2023-07-28
  • 最后修改日期:2023-09-08
  • 接受日期:2023-08-29
  • 在线发布日期: 2023-10-20
  • 出版日期: 2023-10-20