Book contents
- Cambridge Handbook of Pain Medicine
- Cambridge Handbook of Pain Medicine
- Copyright page
- Contents
- Contributors
- Pain Handbook Introduction
- Part I Introduction to Pain: Pain Signaling Pathways
- Chapter 1 Central Neuropathic Pain Signaling Pathways
- Chapter 2 Cannabinoids Pain Signaling Pathways
- Chapter 3 The Microbiome and Chronic Pain Syndromes
- Part II Common Categories of Pharmacologic Medications to Treat Chronic Pain
- Part III Chronic Pain Conditions Head and Neck
- Part IV Spine
- Part V Extremities
- Part VI Misc
- Part VII Adjunctive Therapy
- Index
- References
Chapter 2 - Cannabinoids Pain Signaling Pathways
from Part I - Introduction to Pain: Pain Signaling Pathways
Published online by Cambridge University Press: 01 December 2023
Book contents
- Cambridge Handbook of Pain Medicine
- Cambridge Handbook of Pain Medicine
- Copyright page
- Contents
- Contributors
- Pain Handbook Introduction
- Part I Introduction to Pain: Pain Signaling Pathways
- Chapter 1 Central Neuropathic Pain Signaling Pathways
- Chapter 2 Cannabinoids Pain Signaling Pathways
- Chapter 3 The Microbiome and Chronic Pain Syndromes
- Part II Common Categories of Pharmacologic Medications to Treat Chronic Pain
- Part III Chronic Pain Conditions Head and Neck
- Part IV Spine
- Part V Extremities
- Part VI Misc
- Part VII Adjunctive Therapy
- Index
- References
Summary
Endogenous cannabinoid system was discovered in the early 1990s. The endocannabinoid system includes cannabinoid receptors, ligands, and metabolic enzymes found within the central nervous system (CNS). Inhibition or slowing of the degradation of endocannabinoids in select tissues may confer analgesic or anxiolytic effects. Cannabinoids are becoming increasingly prescribed and studied as potential analgesic agents. Cannabinoid therapy may offer a viable alternative to opioids for management of chronic pain. Studies have demonstrated the presence of endocannabinoids and cannabinoid receptors throughout the nervous system. Cannabinoids have been shown to induce analgesic effects through mechanisms different from traditional antinociceptive pathways. Investigations of the clinical applications of cannabinoids have been limited. Clinical trials suggest that extracts containing THC or its derivatives may be efficacious in the treatment of inflammatory, neuropathic, and oncologic pain. Pharmacologic agents aimed at increasing levels of endogenous endocannabinoids may represent an alternative way of producing analgesia. There is a need for further double-blinded placebo-controlled clinicals to support the use of cannabinoids for pain control.
- Type
- Chapter
- Information
- Cambridge Handbook of Pain Medicine , pp. 14 - 25Publisher: Cambridge University PressPrint publication year: 2023
References
Starowicz, K, Finn, DP. Cannabinoids and pain: Sites and mechanisms of action. Adv Pharmacol Sci. 2017;80:437–475.CrossRefGoogle ScholarPubMed
Di Marzo, V, Fontana, A, Cadas, H, Schinelli, S, Cimino, G, Schwartz, J-C, Piomelli, D. Formation and inactivation of endogenous cannabinoid anandamide in central neurons. Nature. 1994;372(6507):686–691.CrossRefGoogle ScholarPubMed
Giuffrida, A, Beltramo, M, Piomelli, D. Mechanisms of endocannabinoid inactivation: Biochemistry and pharmacology. J Pharmacol Exp Ther. 2001;298(1):7–14.Google Scholar
Parolaro, D, Realini, N, Vigano, D, Guidali, C, Rubino, T. The endocannabinoid system and psychiatric disorders. Exp Neurol. 2010;224(1):3–14.CrossRefGoogle ScholarPubMed
Manzanares, J, Julian, M, Carrascosa, A. Role of the cannabinoid system in pain control and therapeutic implications for the management of acute and chronic pain episodes. Curr Neuropharmacol. 2006;4(3):239–257.CrossRefGoogle ScholarPubMed
Walker, JM, Krey, JF, Chu, CJ, Huang, SM. Endocannabinoids and related fatty acid derivatives in pain modulation. Chem Phys Lipids. 2002;121(1–2):159–172.CrossRefGoogle ScholarPubMed
Devane, WA, Hanus, L, Breuer, A, Pertwee, RG, Stevenson, LA, Griffin, G, Gibson, D, Mandelbaum, A, Etinger, A, Mechoulam, R. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science. 1992;258(5090):1946–1949.CrossRefGoogle Scholar
Mechoulam, R, Ben-Shabat, S, Hanus, L, Ligumsky, M, Kaminski, NE, Schatz, AR, Gopher, A, Almog, S, Martin, BR, Compton, DR. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol. 1995;50(1):83–90.CrossRefGoogle ScholarPubMed
Porter, AC, Sauer, J-M, Knierman, MD, Becker, GW, Berna, MJ, Bao, J, Nomikos, GG, Carter, P, Bymaster, FP, Leese, AB, Felder, CC. Characterization of a novel endocannabinoid, virodhamine, with antagonist activity at the CB1 receptor. J Pharmacol Exp Ther. 2002;301(3):1020–1024.CrossRefGoogle ScholarPubMed
Mackie, K. Cannabinoid receptors: Where they are and what they do. J Neuroendocrinol. 2008;20(s1):10–14.CrossRefGoogle Scholar
Sañudo-Peña, MC, Strangman, NM, Mackie, K, Walker, JM, Tsou, K. CB1 receptor localization in rat spinal cord and roots, dorsal root ganglion, and peripheral nerve. Zhongguo Yao Li Xue Bao. 1999;20(12):1115–1120.Google ScholarPubMed
Manning, BH, Martin, WJ, Meng, ID. The rodent amygdala contributes to the production of cannabinoid-induced antinociception. Neuroscience. 2003;120(4):1157–1170.CrossRefGoogle Scholar
Martin, WJ, Hohmann, AG, Walker, JM. Suppression of noxious stimulus-evoked activity in the ventral posterolateral nucleus of the thalamus by a cannabinoid agonist: Correlation between electrophysiological and antinociceptive effects. J Neurosci. 1996;16(20):6601–6611.CrossRefGoogle ScholarPubMed
Lichtman, AH, Cook, SA, Martin, BR. Investigation of brain sites mediating cannabinoid-induced antinociception in rats: Evidence supporting periaqueductal gray involvement. J Pharmacol Exp Ther. 1996;276(2):585–593.Google ScholarPubMed
Luo, C, Kumamoto, E, Furue, H, Chen, J, Yoshimura, M. Anandamide inhibits excitatory transmission to rat substantia gelatinosa neurones in a manner different from that of capsaicin. Neurosci Lett. 2002;321(1–2):17–20.CrossRefGoogle Scholar
Morisset, V, Urban, L. Cannabinoid-induced presynaptic inhibition of glutamatergic EPSCs in substantia gelatinosa neurons of the rat spinal cord. J Neurophysiol. 2001;86(1):40–48.CrossRefGoogle ScholarPubMed
Bridges, D, Rice, ASC, Egertová, M, Elphick, MR, Winter, J, Michael, GJ. Localisation of cannabinoid receptor 1 in rat dorsal root ganglion using in situ hybridisation and immunohistochemistry. Neuroscience. 2003;119(3):803–812.CrossRefGoogle ScholarPubMed
Hill, KP, Palastro, MD, Johnson, B, Ditre, JW. Cannabis and pain: A clinical review. Cannabis cannabinoid Res. 2017;2(1):96–104.CrossRefGoogle Scholar
Ibrahim, MM, Porreca, F, Lai, J, Albrecht, PJ, Rice, FL, Khodorova, A, Davar, G, Makriyannis, A, Vanderah, TW, Mata, HP, Malan, TP. CB2 cannabinoid receptor activation produces antinociception by stimulating peripheral release of endogenous opioids. Proc Natl Acad Sci. 2005;102(8):3093–3098.CrossRefGoogle ScholarPubMed
Abrams, D, Guzman, M. Cannabis in cancer care. Clin Pharmacol Ther. 2015;97(6):575–586.CrossRefGoogle ScholarPubMed
Scavone, JL, Sterling, RC, Van Bockstaele, EJ. Cannabinoid and opioid interactions: Implications for opiate dependence and withdrawal. Neuroscience. 2013;248:637–654.CrossRefGoogle ScholarPubMed
Pertwee, RG. Endocannabinoids and their pharmacological actions. Handb. Exp. Pharmacol. 2015;231:1–37. doi: 10.1007/978-3-319-20825-1_1.CrossRefGoogle ScholarPubMed
Katona, I, Sperlágh, B, Maglóczky, Z, Sántha, E, Köfalvi, A, Czirják, S, Mackie, K, Vizi, ES, Freund, TF. GABAergic interneurons are the targets of cannabinoid actions in the human hippocampus. Neuroscience. 2000;100(4):797–804.CrossRefGoogle ScholarPubMed
Schlicker, E, Kathmann, M. Modulation of transmitter release via presynaptic cannabinoid receptors. Trends Pharmacol Sci. 2001;22(11):565–572.CrossRefGoogle ScholarPubMed
Ibsen, MS, Connor, M, Glass, M. Cannabinoid CB 1 and CB 2 receptor signaling and bias. Cannabis Cannabinoid Res. 2017;2(1):48–60.CrossRefGoogle ScholarPubMed
Niu, J, Huang, D, Zhou, R, Yue, M, Xu, T, Yang, J, He, L, Tian, H, Liu, X, Zeng, J. Activation of dorsal horn cannabinoid CB2 receptor suppresses the expression of P2Y12 and P2Y13 receptors in neuropathic pain rats. J Neuroinflammation. 2017;14(1):185.CrossRefGoogle ScholarPubMed
Fine, PG, Rosenfeld, MJ. The endocannabinoid system, cannabinoids, and pain. Rambam Maimonides Med J. 2013;4(4):e0022.CrossRefGoogle ScholarPubMed
Lowin, T, Straub, RH. Cannabinoid-based drugs targeting CB1 and TRPV1, the sympathetic nervous system, and arthritis. Arthritis Res Ther. 2015;17(1):226.CrossRefGoogle ScholarPubMed
Cristino, L, de Petrocellis, L, Pryce, G, Baker, D, Guglielmotti, V, Di Marzo, V. Immunohistochemical localization of cannabinoid type 1 and vanilloid transient receptor potential vanilloid type 1 receptors in the mouse brain. Neuroscience. 2006;139(4):1405–1415.CrossRefGoogle ScholarPubMed
Rahn, EJ, Hohmann, AG. Cannabinoids as pharmacotherapies for neuropathic pain: from the bench to the bedside. Neurotherapeutics. 2009;6(4):713–737.CrossRefGoogle Scholar
Gui, H, Liu, X, Liu, L-R, Su, D-F, Dai, S-M. Activation of cannabinoid receptor 2 attenuates synovitis and joint destruction in collagen-induced arthritis. Immunobiology. 2015;220(6):817–822.CrossRefGoogle ScholarPubMed
Toth, CC, Jedrzejewski, NM, Ellis, CL, Frey, WH. Cannabinoid-mediated modulation of neuropathic pain and microglial accumulation in a model of murine type I diabetic peripheral neuropathic pain. Mol Pain. 2010;6:1744–8069.CrossRefGoogle Scholar
Nielsen, S, Sabioni, P, Trigo, JM, Ware, MA, Betz-Stablein, BD, Murnion, B, Lintzeris, N, Khor, KE, Farrell, M, Smith, A, Le Foll, B. Opioid-sparing effect of cannabinoids: A systematic review and meta-analysis. Neuropsychopharmacology. 2017;42(9):1752–1765.CrossRefGoogle ScholarPubMed
Hojo, M, Sudo, Y, Ando, Y, Minami, K, Takada, M, Matsubara, T, Kanaide, M, Taniyama, K, Sumikawa, K, Uezono, Y. μ-Opioid receptor forms a functional heterodimer with cannabinoid CB1 receptor: Electrophysiological and FRET assay analysis. J Pharmacol Sci. 2008;108(3):308–319.CrossRefGoogle ScholarPubMed
Salio, C, Fischer, J, Franzoni, MF et al. CB1-cannabinoid and μ -Opioid receptor co-localization on postsynaptic target in the rat dorsal horn. Neuroreport. 2001;12(17):3689–3692.CrossRefGoogle ScholarPubMed
Cathel, AM, Reyes, BAS, Wang, Q et al. Cannabinoid modulation of alpha2 adrenergic receptor function in rodent medial prefrontal cortex. Eur J Neurosci. 2014;40(8):3202–3214.CrossRefGoogle ScholarPubMed
Takeda, S, Misawa, K, Yamamoto, I, Watanabe, K. Cannabidiolic acid as a selective cyclooxygenase-2 inhibitory component in cannabis. Drug Metab Dispos. 2008;36(9):1917–1921.CrossRefGoogle ScholarPubMed
Romero-Sandoval, EA, Kolano, AL, Alvarado-Vázquez, PA. Cannabis and cannabinoids for chronic pain. Curr Rheumatol Rep. 2017;19(11):67.CrossRefGoogle ScholarPubMed
Rai, A, Meng, H, Weinrib, A, Englesakis, M. A review of adjunctive CNS medications used for the treatment of post-surgical pain. CNS Drugs. 2017;31(7):605–615.CrossRefGoogle ScholarPubMed
Kleine-brueggeney, M, Greif, R, Brenneisen, R et al. Intravenous delta-9-tetrahydrocannabinol to prevent postoperative nausea and vomiting: A randomized controlled trial. Anesth Analg. 2015;121(5).CrossRefGoogle ScholarPubMed
Khelemsky, Y, Goldberg, AT, Hurd, YL et al. Perioperative patient beliefs regarding potential effectiveness of marijuana (cannabinoids) for treatment of pain: A prospective population survey. Reg Anesth Pain Med. 2017;42(5):652–659.CrossRefGoogle Scholar
Meng, H, Johnston, B, Englesakis, M et al. Selective cannabinoids for chronic neuropathic pain: A systemic review and meta-analysis. Anesth Analg. 2017;125(5):1638–1652.CrossRefGoogle Scholar
Fitzcharles, M-A, Baerwald, C, Ablin, J, Häuser, W. Efficacy, tolerability and safety of cannabinoids in chronic pain associated with rheumatic diseases (fibromyalgia syndrome, rheumatoid arthritis): A systematic review of randomized controlled trials. Schmerz (Berlin, Germany). 2016;30(1):47–61.CrossRefGoogle ScholarPubMed
Karst, M, Salim, K, Burstein, S et al. Analgesic effect of the synthetic cannabinoid CT-3 on chronic neuropathic pain. JAMA. 2003;290(13):1757.CrossRefGoogle ScholarPubMed
Hall, N, Eldabe, S. Phantom limb pain: A review of pharmacological management. Br J Pain. 2018;12(4):202–207.CrossRefGoogle ScholarPubMed
Russo, EB. Cannabis Therapeutics and the Future of Neurology. Front Integr Neurosci. 2018;12:51.CrossRefGoogle ScholarPubMed
Davis, MP. Cannabinoids for symptom management and cancer therapy: The evidence. J Natl Compr Canc Netw. 2016;14(7):915–922.CrossRefGoogle ScholarPubMed
Kenyon, J, Liu, W, Dalgleish, A. Report of objective clinical responses of cancer patients to pharmaceutical-grade synthetic cannabidiol. Anticancer Res. 2018;38(10):5831–5835.CrossRefGoogle ScholarPubMed
Baron, EP. Medicinal properties of cannabinoids, terpenes, and flavonoids in cannabis, and benefits in migraine, headache, and pain: An update on current evidence and cannabis science. Headache J Head Face Pain. 2018;58(7):1139–1186.CrossRefGoogle ScholarPubMed
Kandasamy, R, Dawson, CT, Craft, RM, Morgan, MM. Anti-migraine effect of Δ 9-tetrahydrocannabinol in the female rat. Eur J Pharmacol. 2018;818:271–277.CrossRefGoogle ScholarPubMed
Pamplona, FA, Phytolab, E, Giniatullin Rashidginiatullin, R et al. Emerging role of (endo)cannabinoids in migraine. Front Pharmacol. 2018;9:420.Google Scholar
Torres-moreno, MC, Papaseit, E, Torrens, M, Farré, M. Assessment of efficacy and tolerability of medicinal cannabinoids in patients with multiple sclerosis: A systematic review and meta-analysis. JAMA. 2018;1(6):1–16.Google ScholarPubMed
Smith, PF. Therapeutics and clinical risk management new approaches in the management of spasticity in multiple sclerosis patients: Role of cannabinoids. Ther Clin Risk Manag. 2010;6:6–59.Google ScholarPubMed
Langford, RM, Mares, J, Novotna, A et al. A double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD oromucosal spray in combination with the existing treatment regimen, in the relief of central neuropathic pain in patients with multiple sclerosis. J Neurol. 2013;260(4):984–997.CrossRefGoogle ScholarPubMed
Russo, EB. Clinical endocannabinoid deficiency reconsidered: Current research supports the theory in migraine, fibromyalgia, irritable bowel, and other treatment-resistant syndromes. Cannabis Cannabinoid Res. 2016;1(1):154–165.CrossRefGoogle ScholarPubMed