内源性大麻素系统在神经病理性疼痛中的作用和研究进展
The Role and Research Progress of the Endocannabinoid System in Neuropathic Pain
DOI: 10.12677/IJPN.2022.113004, PDF,   
作者: 刘雅妮：三峡大学国家中医药管理局中药药理科研三级实验室，湖北 宜昌;三峡大学医学院机能学系，湖北 宜昌；杨红卫, 陆永利*：三峡大学国家中医药管理局中药药理科研三级实验室，湖北 宜昌;三峡大学医学院机能学系，湖北 宜昌;三峡大学脑重大疾病研究所，湖北 宜昌
关键词: 内源性大麻素系统；神经病理性疼痛；Endocannabinoid System； Neuropathic Pain
摘要: 神经病理性疼痛(Neuropathic pain, NP)作为慢性疼痛的常见来源，其发病机制复杂且目前尚无有效治疗手段；又因其发病时产生持续的灼烧似疼痛而严重影响患者的正常生活，给个人和社会带来沉重负担。内源性大麻素系统(Endocannabinoid System, ECS)已被证实是内源性抗伤害系统的一部分, 包含多个有前景的NP治疗靶点：目前研究表明激活外周CB1受体通路、靶向激活CB2受体、抑制内源性大麻素降解酶和调节瞬态受体电位通道(TRP)等都是有效减轻NP症状的策略。本文主要从上述四个方面对ECS在疼痛管理中的作用和分子机制及相关NP治疗靶点的研究进展做一综述，以期为NP的治疗及ECS相关药物的开发提供理论支持。
Abstract: Neuropathic pain (NP) is a common source of chronic pain. The pathogenesis of NP is complex and there is no effective treatment at present. Its onset can produce continuous burning pain and affect the normal life of patients seriously. NP imposes a heavy burden on individuals and society. The endocannabinoid system (ECS) has been proven to be a part of the endogenous anti-injury system and contains several promising NP therapeutic targets: current studies have demonstrated that activating peripheral CB1 receptor pathway, targeting activating CB2 receptors, inhibiting endocannabinoid degrading enzymes and regulating transient receptor potential channels (TRP) are potentially effective strategies for alleviating NP symptoms. In this paper, in order to provide theoretical support for the treatment of NP and the development of ECS-related drugs, the role and molecular mechanism of ECS in pain management and related NP therapeutic targets were reviewed from the above four aspects.
文章引用：刘雅妮, 杨红卫, 陆永利. 内源性大麻素系统在神经病理性疼痛中的作用和研究进展[J]. 国际神经精神科学杂志, 2022, 11(3): 19-26. https://doi.org/10.12677/IJPN.2022.113004

参考文献

[1] Donvito, G., Nass, S.R., Wilkerson, J.L., et al. (2018) The Endogenous Cannabinoid System: A Budding Source of Targets for Treating Inflammatory and Neuropathic Pain. Neuropsychopharmacology, 43, 52-79. [Google Scholar] [CrossRef] [PubMed]
[2] Bán, E.G., Brassai, A. and Vizi, E.S. (2020) The Role of the Endoge-nous Neurotransmitters Associated with Neuropathic Pain and in the Opioid Crisis: The Innate Pain-Relieving System. Brain Research Bulletin, 155, 129-136. [Google Scholar] [CrossRef] [PubMed]
[3] Stasiulewicz, A., Znajdek, K., Grudzień, M., et al. (2020) A Guide to Targeting the Endocannabinoid System in Drug Design. International Journal of Molecular Sciences, 21, Arti-cle 2778. [Google Scholar] [CrossRef] [PubMed]
[4] Wu, J. (2019) Cannabis, Cannabinoid Receptors, and Endo-cannabinoid System: Yesterday, Today, and Tomorrow. Acta Pharmaceutica Sinica, 40, 297-299. [Google Scholar] [CrossRef] [PubMed]
[5] Anthony, A.T., Rahmat, S., Sangle, P., et al. (2020) Cannabinoid Receptors and Their Relationship with Chronic Pain: A Narrative Review. Cureus, 12, e10436. [Google Scholar] [CrossRef] [PubMed]
[6] Estrada, J.A. and Contreras, I. (2020) Endocannabinoid Receptors in the CNS: Potential Drug Targets for the Prevention and Treatment of Neurologic and Psychiatric Disorders. Current Neuro-pharmacology, 18, 769-787. [Google Scholar] [CrossRef] 
[7] Ahmed, I., Rehman, S.U., Shahmohamadnejad, S., et al. (2021) Therapeutic Attributes of Endocannabinoid System against Neuro-Inflammatory Autoimmune Disorders. Molecules, 26, Article 3389. [Google Scholar] [CrossRef] [PubMed]
[8] 陈华伦. 慢性疼痛神经生理机制的研究进展[J]. 重庆医学, 2021, 50(10): 1777-1781. [Google Scholar] [CrossRef] 
[9] Szok, D., Tajti, J., Nyári, A., et al. (2019) Therapeutic Approaches for Peripheral and Central Neuropathic Pain. Behavioural Neurology, 2019, Article ID: 8685954. [Google Scholar] [CrossRef] [PubMed]
[10] 刘杰, 杨晓秋. 定量感觉检查在神经病理性疼痛的应用研究进展[J]. 中国疼痛学杂志, 2017, 23(10): 768-773. [Google Scholar] [CrossRef] 
[11] Zou, S. and Kumar, U. (2018) Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System. International Journal of Mo-lecular Sciences, 19, Article 833. [Google Scholar] [CrossRef] [PubMed]
[12] Milligan, A.L., Szabo-Pardi, T.A. and Burton, M.D. (2020) Canna-binoid Receptor Type 1 and Its Role as an Analgesic: An Opioid Alternative? Journal of Dual Diagnosis, 16, 106-119. [Google Scholar] [CrossRef] [PubMed]
[13] Parsons, L.H. and Hurd, Y.L. (2015) Endocannabinoid Sig-naling in Reward and Addiction. Nature Reviews Neuroscience, 16, 579-594. [Google Scholar] [CrossRef] [PubMed]
[14] Bie, B., Wu, J., Foss, J.F., et al. (2018) An Overview of the Cannabinoid Type 2 Receptor System and Its Therapeutic Potential. Current Opinion in Anesthesiology, 31, 407-414. [Google Scholar] [CrossRef] 
[15] Nent, E., Nozaki, C., Schmöle, A.C., et al. (2019) CB2 Re-ceptor Deletion on Myeloid Cells Enhanced Mechanical Allodynia in a Mouse Model of Neuropathic Pain. Scientific Re-ports, 9, Article No. 7468. [Google Scholar] [CrossRef] [PubMed]
[16] Clark, A.K., Yip, P.K., Grist, J., et al. (2007) Inhibition of Spinal Microglial Cathepsin S for the Reversal of Neuropathic Pain. Proceedings of the National Academy of Sciences of the United States of America, 104, 10655-10660. [Google Scholar] [CrossRef] [PubMed]
[17] Malek, N., Popiolek-Barczyk, K., Mika, J., et al. (2015) Anan-damide, Acting via CB2 Receptors, Alleviates LPS-Induced Neuroinflammation in Rat Primary Microglial Cultures. Neural Plasticity, 2015, Article ID: 130639. [Google Scholar] [CrossRef] [PubMed]
[18] Gado, F., Di Cesare Mannelli, L., Lucarini, E., et al. (2019) Identification of the First Synthetic Allosteric Modulator of the CB(2) Receptors and Evidence of Its Efficacy for Neuropathic Pain Re-lief. Journal of Medicinal Chemistry, 62, 276-287. [Google Scholar] [CrossRef] [PubMed]
[19] Tripathi, R.K.P. (2020) A Perspective Review on Fatty Acid Amide Hydrolase (FAAH) Inhibitors as Potential Therapeutic Agents. European Journal of Medicinal Chemistry, 188, Article ID: 111953. [Google Scholar] [CrossRef] [PubMed]
[20] Wallace, V.C., Segerdahl, A.R., Lambert, D.M., et al. (2007) The Effect of the Palmitoylethanolamide Analogue, Palmitoylallylamide (L-29) on Pain Behaviour in Rodent Models of Neuropathy. British Journal of Pharmacology, 151, 1117-1128. [Google Scholar] [CrossRef] [PubMed]
[21] Wiskerke, J., Irimia, C., Cravatt, B.F., et al. (2012) Characterization of the Effects of Reuptake and Hydrolysis Inhibition on Interstitial Endocannabinoid Levels in the Brain: An in Vivo Micro-dialysis Study. ACS Chemical Neuroscience, 3, 407-417. [Google Scholar] [CrossRef] [PubMed]
[22] Ignatowska-Jankowska, B., Wilkerson, J.L., Mustafa, M., et al. (2015) Selective Monoacylglycerol Lipase Inhibitors: Antinociceptive versus Cannabimimetic Effects in Mice. Journal of Phar-macology and Experimental Therapeutics, 353, 424-432. [Google Scholar] [CrossRef] [PubMed]
[23] Hossain, M.Z. ando, H., Unno, S., et al. (2020) Targeting Peripherally Restricted Cannabinoid Receptor 1, Cannabinoid Receptor 2, and Endocannabinoid-Degrading Enzymes for the Treatment of Neuropathic Pain Including Neuropathic Orofacial Pain. International Journal of Molecular Sciences, 21, Article 1423. [Google Scholar] [CrossRef] [PubMed]
[24] Kaczocha, M., Glaser, S.T., Maher, T., et al. (2015) Fatty Acid Binding Protein Deletion Suppresses Inflammatory Pain through Endocannabinoid/N-acylethanolamine-Dependent Mechanisms. Molecular Pain, 11, Article No. 52. [Google Scholar] [CrossRef] [PubMed]
[25] Kaczocha, M., Rebecchi, M.J., Ralph, B.P., et al. (2014) Inhibi-tion of Fatty Acid Binding Proteins Elevates Brain Anandamide Levels and Produces Analgesia. PLOS ONE, 9, e94200. [Google Scholar] [CrossRef] [PubMed]
[26] Muller, C., Morales, P. and Reggio, P.H. (2019) Cannabinoid Ligands Targeting TRP Channels. Frontiers in Molecular Neuroscience, 11, Article No. 487. [Google Scholar] [CrossRef] [PubMed]
[27] Xiang, H., Liu, Z., Wang, F., et al. (2017) Primary Sensory Neu-ron-Specific Interference of TRPV1 Signaling by AAV-Encoded TRPV1 Peptide Aptamer Attenuates Neuropathic Pain. Molecular Pain, 13, 1-18. [Google Scholar] [CrossRef] [PubMed]
[28] Starowicz, K. and Finn, D.P. (2017) Cannabinoids and Pain: Sites and Mechanisms of Action. Advances in Pharmacology, 80, 437-475. [Google Scholar] [CrossRef] [PubMed]