Volume 27, Issue 2 (July 2023)                   Physiol Pharmacol 2023, 27(2): 100-115 | Back to browse issues page

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Marcos Guimarães de Souza G, Dias-Souza M V. Neuropharmacology of endogenous, synthetic and phytocannabinoids for pain management. Physiol Pharmacol 2023; 27 (2) :100-115
URL: http://ppj.phypha.ir/article-1-1883-en.html
Neuropharmacology of endogenous, synthetic and phytocannabinoids for pain management
Geovane Marcos Guimarães de Souza , Marcus Vinicius Dias-Souza
Abstract:   (1142 Views)
The use of cannabis-derived compounds for medical purposes dates from more than two thousand years. Due to its psychotropic effects and cultural aspects related to the plant of origin, its benefits have been disregarded in several western countries. Nevertheless, the number of studies on Cannabis sativa, especially on clinical applications of cannabinoids, increased significantly in the latest years. Amidst the benefits of cannabis-derived compounds is pain relief. Here we review physiological, pharmacological and chemical aspects of pain management in humans with endocannabinoids, synthetic cannabinoids and phytocannabinoids. The analgesia mechanism can be explained not only through interactions with cannabinoid receptors 1 and 2 but also through direct or indirect interaction with serotonin, glycine, gamma-aminobutyric acid, N-methyl-D-aspartate, adrenergic and opioid receptors, as well as transient receptors potential channels. They can also modify the behavior of molecules such as cytokines, calcitonin gene-related protein and substance P, which largely influence pain-related mechanisms. Exogenous cannabinoids are interesting options to consider when it comes to pain management, especially in complex cases associated to poor response to the currently available drug therapy
Keywords: Neuropharmacology, Cannabinoids, Phytocannabinoids, Endocannabinoids, Pain
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Type of Manuscript: Review | Subject: Blood and Immune System
References
1. Almeida TF, Roizenblatt S, Tufik S. Afferent pain pathways: a neuroanatomical review. Brain Res 2004; 1000: 40-56. [DOI:10.1016/j.brainres.2003.10.073]
2. Amin MR, Ali DW. Pharmacology of medical cannabis. Adv Exp Med Biol 2019; 1162: 151-65. [DOI:10.1007/978-3-030-21737-2_8]
3. Andre CM, Hausman JF, Guerriero G. Cannabis sativa: the plant of the thousand and one molecules. Front Plant Sci 2016; 7: 19. [DOI:10.3389/fpls.2016.00019]
4. Anwar K. Pathophysiology of pain. Dis Mon 2016; 62: 324-9. [DOI:10.1016/j.disamonth.2016.05.015]
5. Araujo DSM, Nassini R, Geppetti P, De Logu F. TRPA1 as a therapeutic target for nociceptive pain. Expert Opin Ther Targets 2020; 24: 997-1008. [DOI:10.1080/14728222.2020.1815191]
6. Argenziano M, Tortora C, Bellini G, Di Paola A, Punzo F, Rossi F. The endocannabinoid system in pediatric inflammatory and immune diseases. Int J Mol Sci 2019; 20: 5875. [DOI:10.3390/ijms20235875]
7. Atalay S, Jarocka-karpowicz I, Skrzydlewskas E. Antioxidative and anti-inflammatory properties of cannabidiol. Antioxidants (Basel) 2020; 9: 21. [DOI:10.3390/antiox9010021]
8. Bagley EE, Ingram SL. Endogenous opioid peptides in the descending pain modulatory circuit. Neuropharmacology 2020; 173:108131. [DOI:10.1016/j.neuropharm.2020.108131]
9. Baliki MN, Apkarian AV. Nociception, pain, negative moods, and behavior selection. Neuron 2015; 87: 474-91. [DOI:10.1016/j.neuron.2015.06.005]
10. Bantel C, Maze M, Stone L, Wilcox G, Schmidt RF, Willis WD. Alpha(α) 2-Adrenergic agonists in pain treatment. Encyclopedia of pain 2007: 58-61. [DOI:10.1007/978-3-540-29805-2_165]
11. Barbosa F A S, Castro E S D, Dias-Souza M V. Pharmacology of Non-steroidal Anti-inflammatory drugs : A Prescription-based Overview. Journal of Applied Pharmaceutical Sciences 2021: 11-20.
12. Baron EP. Comprehensive review of medicinal marijuana, cannabinoids, and therapeutic implications in medicine and headache: What a long strange trip it’s been .... Headache 2015; 55: 885-916. [DOI:10.1111/head.12570]
13. Baur R, Gertsch J, Sigel E. The cannabinoid CB1 receptor antagonists rimonabant (SR141716) and AM251 directly potentiate GABA(A) receptors. Br J Pharmacol 2012; 165: 2479-84. [DOI:10.1111/j.1476-5381.2011.01405.x]
14. Bell A. The neurobiology of acute pain. Vet J 2018; 237: 55-62. [DOI:10.1016/j.tvjl.2018.05.004]
15. Benítez-Angeles M, Morales-Lázaro SL, Juárez-González E, Rosenbaum T. TRPV1: structure, endogenous agonists, and mechanisms. Int J Mol Sci 2020; 21: 3421. [DOI:10.3390/ijms21103421]
16. Bonini SA, Premoli M, Tambaro S, Kumar A, Maccarinelli G, Memo M, et al. Cannabis sativa: A comprehensive ethnopharmacological review of a medicinal plant with a long history. J Ethnopharmacol 2018; 227: 300-15. [DOI:10.1016/j.jep.2018.09.004]
17. Bourne S, Machado AG, Nagel SJ. Basic anatomy and physiology of pain pathways. Neurosurg Clin N Am 2014; 25: 629-38. [DOI:10.1016/j.nec.2014.06.001]
18. Carranza RR. Los productos de cannabis sativa: Situación actual y perspectivas en medicina. Salud Mental 2012; 35: 247-56.
19. Cathel AM, Reyes BA, Wang Q, Palma J, Mackie K, Van Bockstaele EJ, et al. Cannabinoid modulation of alpha2 adrenergic receptor function in rodent medial prefrontal cortex. Eur J Neurosci 2014; 40: 3202-14. [DOI:10.1111/ejn.12690]
20. Chen Q, Heinricher MM. Descending control mechanisms and chronic pain. Curr Rheumatol Rep 2019; 21:13. [DOI:10.1007/s11926-019-0813-1]
21. Cristino L, Bisogno T, Di Marzo V. Cannabinoids and the expanded endocannabinoid system in neurological disorders. Nat Rev Neurol 2020; 16: 9-29. [DOI:10.1038/s41582-019-0284-z]
22. Csekő K, Beckers B, Keszthelyi D, Helyes Z. Role of TRPV1 and TRPA1 ion channels in inflammatory bowel diseases: potential therapeutic targets? Pharmaceuticals (Basel) 2019; 12: 48. [DOI:10.3390/ph12020048]
23. Datta U, Kelley LK, Middleton JW, Gilpin NW. Positive allosteric modulation of the cannabinoid type-1 receptor (CB1R) in periaqueductal gray (PAG) antagonizes anti-nociceptive and cellular effects of a mu-opioid receptor agonist in morphine-withdrawn rats. Psychopharmacology (Berl) 2020; 237: 3729-39. [DOI:10.1007/s00213-020-05650-5]
24. Danilov AB, Isagilyan ED, Mackaschova ES. Psychogenic pain. Zh Nevrol Psikhiatr Im S S Korsakova 2018; 118: 103-8. [DOI:10.17116/jnevro2018118111103]
25. De Petrocellis L, Orlando P, Moriello AS, Aviello G, Stott C, Izzo AA, et al. Cannabinoid actions at TRPV channels: effects on TRPV3 and TRPV4 and their potential relevance to gastrointestinal inflammation. Acta Physiol (Oxf) 2012; 204: 255-66. [DOI:10.1111/j.1748-1716.2011.02338.x]
26. DeSantana JM, Perissinotti DMN, Oliveira Junior JOd, Correia LMF, Oliveira CMd, Fonseca PRBd. Revised definition of pain after four decades. BrJP 2020; 3: 197-8. [DOI:10.5935/2595-0118.20200191]
27. Di Marzo V. The endocannabinoidome as a substrate for noneuphoric phytocannabinoid action and gut microbiome dysfunction in neuropsychiatric disorders. Dialogues Clin Neurosci 2020; 22: 259-69. [DOI:10.31887/DCNS.2020.22.3/vdimarzo]
28. Di Marzo V, Piscitelli F. The endocannabinoid system and its modulation by phytocannabinoids. Neurotherapeutics 2015; 12: 692-8. [DOI:10.1007/s13311-015-0374-6]
29. Dinakar P, Stillman AM. Pathogenesis of pain. Semin Pediatr Neurol 2016; 23: 201-8. [DOI:10.1016/j.spen.2016.10.003]
30. Dos Santos RS, Sorgi CA, Peti APF, Veras FP, Faccioli LH, Galdino G. Involvement of spinal cannabinoid CB2 receptors in exercise-induced antinociception. Neuroscience 2019; 418: 177-88. [DOI:10.1016/j.neuroscience.2019.08.041]
31. Dunne FJ, Getachew H, Cullenbrooke F, Dunne C. Pain and pain syndromes. Br J Hosp Med (Lond). 2018; 79: 449-53. [DOI:10.12968/hmed.2018.79.8.449]
32. Fantegrossi WE, Wilson CD, Berquist MD. Pro-psychotic effects of synthetic cannabinoids: interactions with central dopamine, serotonin, and glutamate systems. Drug Metab Rev 2018; 50: 65-73. [DOI:10.1080/03602532.2018.1428343]
33. Ferdousi M, Finn DP. Stress-induced modulation of pain: role of the endogenous opioid system. Prog Brain Res 2018; 239: 121-77. [DOI:10.1016/bs.pbr.2018.07.002]
34. Fernández-Ruiz J, Sagredo O, Pazos MR, García C, Pertwee R, Mechoulam R, et al. Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid?. Br J Clin Pharmacol 2013; 75: 323-33. [DOI:10.1111/j.1365-2125.2012.04341.x]
35. Fraguas-Sanchez AI, Torres-Suarez AI. Medical use of cannabinoids. Drugs 2018; 78: 1665-703. [DOI:10.1007/s40265-018-0996-1]
36. Gregus AM, Buczynski MW. Druggable targets in endocannabinoid signaling. Adv Exp Med Biol 2020; 1274: 177-201. [DOI:10.1007/978-3-030-50621-6_8]
37. Gresch P J. Serotonin Receptor Signaling. Encyclopedia of Biological Chemistry: Second Edition 2013; 4: 224-228.
38. Grimaldi C, Capasso A. The endocannabinoid system in the cancer therapy: an overview. Curr Med Chem 2011; 18: 1575-83. [DOI:10.2174/092986711795471374]
39. GSK. Global Pain Index 2017 Research Report. Journal 2017: 1-49.
40. Guerrero-Alba R, Barragán-Iglesias P, González-Hernández A, Valdez-Moráles EE, Granados-Soto V, Condés-Lara M, et al. Some prospective alternatives for treating pain: The endocannabinoid system and its putative receptors GPR18 and GPR55. Front Pharmacol 2019; 9: 1496. [DOI:10.3389/fphar.2018.01496]
41. Haack M, Simpson N, Sethna N, Kaur S, Mullington J. Sleep deficiency and chronic pain: potential underlying mechanisms and clinical implications. Neuropsychopharmacology 2020; 45: 205-16. [DOI:10.1038/s41386-019-0439-z]
42. Hanuš LO, Meyer SM, Muñoz E, Taglialatela-Scafati O, Appendino G. Phytocannabinoids: a unified critical inventory. Nat Prod Rep 2016; 33: 1357-92. [DOI:10.1039/C6NP00074F]
43. Hieble JP. Adrenergic receptors. Encyclopedia of Neuroscience, Elsevier Ltd, Academic Press, 2009, pp. 135-39. [DOI:10.1016/B978-008045046-9.00694-X]
44. Hill KP, Palastro MD, Johnson B, Ditre JW. Cannabis and pain: a clinical review. Cannabis Cannabinoid Res 2017; 2: 96-104. [DOI:10.1089/can.2017.0017]
45. Hohmann AG, Suplita RL, Bolton NM, Neely MH, Fegley D, Mangieri R, et al. An endocannabinoid mechanism for stress-induced analgesia. Nature 2005; 435: 1108-12. [DOI:10.1038/nature03658]
46. Howlett AC, Abood ME. CB1 and CB2 receptor pharmacology. Adv Pharmacol 2017; 80: 169-206. [DOI:10.1016/bs.apha.2017.03.007]
47. Huang M, Wang X, Xing B, Yang H, Sa Z, Zhang D, et al. Critical roles of TRPV2 channels, histamine H1 and adenosine A1 receptors in the initiation of acupoint signals for acupuncture analgesia. Sci Rep 2018; 8: 6523. [DOI:10.1038/s41598-018-24654-y]
48. Iftinca M, Altier C. The cool things to know about TRPM8!. Channels (Austin) 2020; 14: 413-20. [DOI:10.1080/19336950.2020.1841419]
49. Janani C, Kumari BDR. PPAR gamma gene--a review. Diabetes Metab Syndr 2015; 9: 46-50. [DOI:10.1016/j.dsx.2014.09.015]
50. Jesus CHA, Redivo DDB, Gasparin AT, Sotomaior BB, de Carvalho MC, Genaro K, et al. Cannabidiol attenuates mechanical allodynia in streptozotocin-induced diabetic rats via serotonergic system activation through 5-HT1A receptors. Brain Res 2019; 1715: 156-64. [DOI:10.1016/j.brainres.2019.03.014]
51. Jewett BE, Thapa B. Physiology, NMDA receptor. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, 2022.
52. Ji RR, Donnelly CR, Nedergaard M. Astrocytes in chronic pain and itch. Nat Rev Neurosci 2019; 20: 667-85. [DOI:10.1038/s41583-019-0218-1]
53. Joshi N, Onaivi ES. Endocannabinoid system components: overview and tissue distribution. Adv Exp Med Biol 2019; 1162: 1-2. [DOI:10.1007/978-3-030-21737-2_1]
54. Kathmann M, Flau K, Redmer A, Tränkle C, Schlicker E. Cannabidiol is an allosteric modulator at mu- and delta-opioid receptors. Naunyn Schmiedebergs Arch Pharmacol 2006; 372: 354-61. [DOI:10.1007/s00210-006-0033-x]
55. Khan A, Khan S, Kim YS. Insight into pain modulation: nociceptors sensitization and therapeutic targets. Curr Drug Targets 2019; 20: 775-88. [DOI:10.2174/1389450120666190131114244]
56. Klinger-Gratz PP, Ralvenius WT, Neumann E, Kato A, Nyilas R, Lele Z, et al. Acetaminophen relieves inflammatory pain through CB1 cannabinoid receptors in the rostral ventromedial medulla. J Neurosci 2018; 38: 322-34. [DOI:10.1523/JNEUROSCI.1945-17.2017]
57. Lauckner JE, Jensen JB, Chen HY, Lu HC, Hille B, Mackie K. GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current. Proc Natl Acad Sci U S A 2008; 105: 2699-704. [DOI:10.1073/pnas.0711278105]
58. Lee GI, Neumeister MW. Pain: pathways and physiology. Clin Plast Surg 2020; 47: 173-80. [DOI:10.1016/j.cps.2019.11.001]
59. Lessa MA, Cavalcanti IL, Figueiredo NV. Cannabinoid derivatives and the pharmacological management of pain. Revista Dor 2016; 17: 47-51. [DOI:10.5935/1806-0013.20160012]
60. Lévêque M, Penna A, Le Trionnaire S, Belleguic C, Desrues B, Brinchault G, et al. Phagocytosis depends on TRPV2-mediated calcium influx and requires TRPV2 in lipids rafts: alteration in macrophages from patients with cystic fibrosis. Sci Rep 2018; 8: 4310. [DOI:10.1038/s41598-018-22558-5]
61. Lötsch J, Weyer-Menkhoff I, Tegeder I. Current evidence of cannabinoid-based analgesia obtained in preclinical and human experimental settings. Eur J Pain 2018; 22: 471-84. [DOI:10.1002/ejp.1148]
62. Lu HC, Mackie K. An introduction to the endogenous cannabinoid system. Biol Psychiatry 2016; 79: 516-25. [DOI:10.1016/j.biopsych.2015.07.028]
63. Lynch JW, Zhang Y, Talwar S, Estrada-Mondragon A. Glycine receptor drug discovery. Adv Pharmacol 2017; 79: 225-53. [DOI:10.1016/bs.apha.2017.01.003]
64. Mansour AR, Farmer MA, Baliki MN, Apkarian AV. Chronic pain: the role of learning and brain plasticity. Restor Neurol Neurosci 2014; 32: 129-39. [DOI:10.3233/RNN-139003]
65. Marchand S. The physiology of pain mechanisms: from the periphery to the brain. Rheum Dis Clin North Am 2008; 34: 285-309. [DOI:10.1016/j.rdc.2008.04.003]
66. Marion-Letellier R, Savoye G, Ghosh S. Fatty acids, eicosanoids and PPAR gamma. Eur J Pharmacol 2016; 785: 44-9. [DOI:10.1016/j.ejphar.2015.11.004]
67. Martínez V, Iriondo De-Hond A, Borrelli F, Capasso R, Del Castillo MD, Abalo R. Cannabidiol and Other non-psychoactive cannabinoids for prevention and treatment of gastrointestinal disorders: useful nutraceuticals? Int J Mol Sci 2020; 21:3067. [DOI:10.3390/ijms21093067]
68. McCarberg B, Peppin J. pain pathways and nervous system plasticity: learning and memory in pain. Pain Med 2019; 20: 2421-37. [DOI:10.1093/pm/pnz017]
69. Mecha M, Carrillo-Salinas FJ, Feliu A, Mestre L, Guaza C. Perspectives on cannabis-based therapy of multiple sclerosis: a mini-review. Front Cell Neurosci 2020; 14: 34. [DOI:10.3389/fncel.2020.00034]
70. Meissner H, Cascella M. Cannabidiol (CBD). StatPearls 2022.
71. Morales P, Hernandez-Folgado L, Goya P, Jagerovic N. Cannabinoid receptor 2 (CB2) agonists and antagonists: a patent update. Expert Opin Ther Pat 2016; 26: 843-56. [DOI:10.1080/13543776.2016.1193157]
72. Morales P, Hurst DP, Reggio PH. Molecular targets of the phytocannabinoids: a complex picture. Prog Chem Org Nat Prod 2017; 103: 103-31. [DOI:10.1007/978-3-319-45541-9_4]
73. Mücke M, Phillips T, Radbruch L, Petzke F, Häuser W. Cannabis-based medicines for chronic neuropathic pain in adults. Cochrane Database Syst Rev 2018; 3: CD012182 [DOI:10.1002/14651858.CD012182.pub2]
74. Muller C, Morales P, Reggio PH. Cannabinoid ligands targeting TRP channels. Front Mol Neurosci 2019; 11: 487. [DOI:10.3389/fnmol.2018.00487]
75. Nachnani R, Raup-Konsavage WM, Vrana KE. The pharmacological case for cannabigerol. J Pharmacol Exp Ther 2021; 376: 204-12. [DOI:10.1124/jpet.120.000340]
76. Navarrete F, García-Gutiérrez MS, Jurado-Barba R, Rubio G, Gasparyan A, Austrich-Olivares A, et al. Endocannabinoid system components as potential biomarkers in psychiatry. Front Psychiatry 2020; 11: 315. [DOI:10.3389/fpsyt.2020.00315]
77. Netzahualcoyotzi-Piedra C, Muñoz-Arenas G, Martínez-García I, Florán-Garduño B, Limón-Pérez ID. La marihuana y el sistema endocanabinoide : De sus efectos recreativos a la terapéutica. Revista Biomédica 2009; 20: 128-53.
78. Neumann A, Engel V, Mahardhika AB, Schoeder CT, Namasivayam V, Kiec-Kononowicz K, et al. Computational investigations on the binding mode of ligands for the cannabinoid-activated g protein-coupled receptor GPR18. Biomolecules 2020; 10: 686. [DOI:10.3390/biom10050686]
79. Nilius B, Biro T, Owsianik G. TRPV3: time to decipher a poorly understood family member! J Physiol 2014; 592: 295-304. [DOI:10.1113/jphysiol.2013.255968]
80. Nilius B, Owsianik G. The transient receptor potential family of ion channels. Genome Biol 2011; 12: 218. [DOI:10.1186/gb-2011-12-3-218]
81. O’Sullivan SE. An update on PPAR activation by cannabinoids. Br J Pharmacol 2016; 173: 1899-910. [DOI:10.1111/bph.13497]
82. Pathan H, Williams J. Basic opioid pharmacology: an update. Br J Pain 2012; 6: 11-6. [DOI:10.1177/2049463712438493]
83. Petroff OA. GABA and glutamate in the human brain. Neuroscientist 2002; 8: 562-73. [DOI:10.1177/1073858402238515]
84. Plant TD, Strotmann R. Trpv4. Handb Exp Pharmacol 2007; 179: 189-205. [DOI:10.1007/978-3-540-34891-7_11]
85. Queremel Milani DA, Davis DD. Pain management medications. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, 2023.
86. Raboune S, Stuart JM, Leishman E, Takacs SM, Rhodes B, Basnet A, et al. Novel endogenous N-acyl amides activate TRPV1-4 receptors, BV-2 microglia, and are regulated in brain in an acute model of inflammation. Front Cell Neurosci 2014; 8: 195. [DOI:10.3389/fncel.2014.00195]
87. Raja SN, Carr DB, Cohen M, Finnerup NB, Flor H, Gibson S, et al. Definição revisada de dor pela Associação Internacional para o Estudo da Dor: conceitos, desafios e compromissos. IASP 2020.
88. Ramer R, Schwarz R, Hinz B. Modulation of the endocannabinoid system as a potential anticancer strategy. Front Pharmacol 2019; 10: 430. [DOI:10.3389/fphar.2019.00430]
89. Rapino C, Tortolani D, Scipioni L, Maccarrone M. Neuroprotection by (endo) cannabinoids in glaucoma and retinal neurodegenerative diseases. Curr Neuropharmacol 2018; 16: 959-70. [DOI:10.2174/1570159X15666170724104305]
90. Rodríguez-Muñoz M, Onetti Y, Cortés-Montero E, Garzón J, Sánchez-Blázquez P. Cannabidiol enhances morphine antinociception, diminishes NMDA-mediated seizures and reduces stroke damage via the sigma 1 receptor. Mol Brain 2018; 11: 51. [DOI:10.1186/s13041-018-0395-2]
91. Rossi F, Tortora C, Argenziano M, Di Paola A, Punzo F. Cannabinoid receptor type 2: a possible target in SARS-CoV-2 (CoV-19) infection? Int J Mol Sci 2020; 21: 3809. [DOI:10.3390/ijms21113809]
92. Russo EB. Cannabinoids in the management of difficult to treat pain. Ther Clin Risk Manag 2008; 4: 245-59. [DOI:10.2147/TCRM.S1928]
93. Russu G, Russu R. Psychogenic pain in children. Rev Med Chir Soc Med Nat Iasi 2008; 112: 327-30.
94. Ryberg E, Larsson N, Sjogren S, Hjorth S, Hermansson NO, Leonova J, et al. The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol 2007; 152: 1092-101. [DOI:10.1038/sj.bjp.0707460]
95. Salami SA, Martinelli F, Giovino A, Bachari A, Arad N, Mantri N. It is our turn to get cannabis high: put cannabinoids in food and health baskets. Molecules 2020; 25: 4036. [DOI:10.3390/molecules25184036]
96. Saliba SW, Jauch H, Gargouri B, Keil A, Hurrle T, Volz N, et al. Anti-neuroinflammatory effects of GPR55 antagonists in LPS-activated primary microglial cells. J Neuroinflammation 2018; 15: 322. [DOI:10.1186/s12974-018-1362-7]
97. Sandkuhler J. Models and mechanisms of hyperalgesia and allodynia. Physiol Rev 2009; 89: 707-58. [DOI:10.1152/physrev.00025.2008]
98. Senn L, Cannazza G, Biagini G. Receptors and channels possibly mediating the effects of phytocannabinoids on seizures and epilepsy. Pharmaceuticals (Basel) 2020; 13: 174. [DOI:10.3390/ph13080174]
99. Shahbazi F, Grandi V, Banerjee A, Trant JF. Cannabinoids and cannabinoid receptors: the story so far. iScience 2020; 23: 101301. [DOI:10.1016/j.isci.2020.101301]
100. Sheth S, Brito R, Mukherjea D, Rybak LP, Ramkumar V. Adenosine receptors: expression, function and regulation. Int J Mol Sci 2014; 15: 2024-52. [DOI:10.3390/ijms15022024]
101. Shi QX, Yang LK, Shi WL, Wang L, Zhou SM, Guan SY, et al. The novel cannabinoid receptor GPR55 mediates anxiolytic-like effects in the medial orbital cortex of mice with acute stress. Mol Brain 2017; 10: 38. [DOI:10.1186/s13041-017-0318-7]
102. Shibasaki K. Physiological significance of TRPV2 as a mechanosensor, thermosensor and lipid sensor. J Physiol Sci 2016; 66: 359-65. [DOI:10.1007/s12576-016-0434-7]
103. Silva JSd, Dias-Souza MV. Tratamento da dor crônica com neuropsicofármacos. JAPHAC 2021: 7: 2-10.
104. Singh AK, McGoldrick LL, Sobolevsky AI. Structure and gating mechanism of the transient receptor potential channel TRPV3. Nat Struct Mol Biol 2018; 25: 805-13. [DOI:10.1038/s41594-018-0108-7]
105. Singh J, Neary JP. Neuroprotection following concussion: the potential role for cannabidiol. Can J Neurol Sci 2020; 47: 289-300. [DOI:10.1017/cjn.2020.23]
106. Sluka KA, Clauw DJ. Neurobiology of fibromyalgia and chronic widespread pain. Neuroscience 2016; 338: 114-29. [DOI:10.1016/j.neuroscience.2016.06.006]
107. Sneddon LU. Comparative physiology of nociception and pain. Physiology (Bethesda) 2018; 33: 63-73.
108. Soares VP, Campos AC. Evidences for the anti-panic actions of cannabidiol. Curr Neuropharmacol 2017; 15: 291-99. [DOI:10.2174/1570159X14666160509123955]
109. Steeds CE. The anatomy and physiology of pain. Surgery (Oxford) 2009; 27: 507-11. [DOI:10.1016/j.mpsur.2009.10.013]
110. Tamba BI, Stanciu GD, Uritu CM, Rezus E, Stefanescu R, Mihai CT, et al. Challenges and opportunities in preclinical research of synthetic cannabinoids for pain therapy. Medicina 2020; 56: 24. [DOI:10.3390/medicina56010024]
111. Tsagareli MG, Nozadze I. An overview on transient receptor potential channels superfamily. Behav Pharmacol 2020; 31: 413-34. [DOI:10.1097/FBP.0000000000000524]
112. Tudurí E, Imbernon M, Hernández-Bautista RJ, Tojo M, Fernø J, Diéguez C, et al. GPR55: a new promising target for metabolism? J Mol Endocrinol 2017; 58: R191-202. [DOI:10.1530/JME-16-0253]
113. Wang L, Hong P J, May C, Rehman Y, Oparin Y, Hong C J, et al. Medical cannabis or cannabinoids for chronic non-cancer and cancer related pain: a systematic review and meta-analysis of randomised clinical trials. BMJ 2021; 374: n1034. [DOI:10.1136/bmj.n1034]
114. WHO. MG30 Chronic pain. ICD-11 - Mortality and Morbidity Statistics 2019.
115. Wróbel A, Serefko A, Szopa A, Ulrich D, Poleszak E, Rechberger T. O-1602, an agonist of atypical cannabinoid receptors GPR55, reverses the symptoms of depression and detrusor overactivity in rats subjected to corticosterone treatment. Front Pharmacol 2020; 11: 1002. [DOI:10.3389/fphar.2020.01002]
116. Xiong W, Cui T, Cheng K, Yang F, Chen SR, Willenbring D, et al. Cannabinoids suppress inflammatory and neuropathic pain by targeting alpha3 glycine receptors. J Exp Med 2012; 209: 1121-34. [DOI:10.1084/jem.20120242]
117. Yang H, Zhou J, Lehmann C. GPR55 - a putative “type 3” cannabinoid receptor in inflammation. J Basic Clin Physiol Pharmacol 2016; 27: 297-302. [DOI:10.1515/jbcpp-2015-0080]
118. Zhou XJ, Yang J, Yan FL, Wang DX, Li XY, Fan XQ, et al. Norepinephrine plays an important role in antinociceptive modulation of hypothalamic paraventricular nucleus in the rat. Int J Neurosci 2010; 120: 428-38. [DOI:10.3109/00207450802333649]
119. Zou G, Zuo X, Chen K, Ge Y, Wang X, Xu G, et al. Cannabinoids rescue cocaine-induced seizures by restoring brain glycine receptor dysfunction. Cell Rep 2020; 30: 4209-19. [DOI:10.1016/j.celrep.2020.02.106]
120. Zuardi AW. History of cannabis as a medicine: a review. Braz J Psychiatry 2006; 28: 153-7. [DOI:10.1590/S1516-44462006000200015]
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