Brazilian Journal of Pain
https://brjp.org.br/article/doi/10.5935/2595-0118.20230029-en
Brazilian Journal of Pain
Review Article

Retrograde inhibition of hyperactive central pathways in nociplastic pain

Inibição retrógrada das vias centrais hiperativas nas dores nociplásticas

Maria Teresa R. J. Jacob; Beatriz Jacob Milani

Downloads: 2
Views: 374

Abstract

BACKGROUND AND OBJECTIVES: Nociplastic pain occurs due to a combination of hyperexcitability and decreased inhibitory activity in the central nervous system, responsible for a state of amplification of different stimuli, present in many chronic disorders. Among them: fibromyalgia, chronic migraine, irritable bowel syndrome, myofascial pain syndrome and complex regional pain syndrome. Often, several of these diseases are associated. Nociplastic pain therapy is a challenge in clinical practice, since most traditional treatments are not effective in controlling symptoms, often causing difficulty in adherence or even interruption of treatment due to undesirable adverse effects. The objective of this article was to demonstrate the importance of identifying the presence of nociplastic pain in the patient’s condition, and also the pathophysiological mechanisms involved. Thus, due to retrograde neuromodulation, a unique feature of the endocannabinoid system until now, evaluate the use of pharmaceutical grade medicines based on the cannabis plant as an adjunct in the therapy of pain and other symptoms associated with this disorder.
CONTENTS: This article was addressed the pathophysiology of nociplastic pain, the physiology to the endocannabinoid system, the cannabis plant with its components and its use as an adjuvant medication in the multimodal treatment of nociplastic pain (due to retrograde neuromodulation), based on published scientific articles between 1981 and 2022.
CONCLUSION: Although the scientific evidence supporting the use of medical cannabis in nociplastic pain therapy is insufficient so far, it can and should be considered as a possible adjuvant medication in multimodal pain therapy, always on an individual basis, when recommended treatments fail or are not tolerated.

Keywords

Cannabis, Chronic pain, Endocannabinoid system, Nociplastic pain

Resumo

JUSTIFICATIVA E OBJETIVOS: A dor nociplástica ocorre por uma combinação de hiperexcitabilidade e diminuição da atividade inibitória no sistema nervoso central, responsável por um estado de amplificação de estímulos diversos, presente em muitas doenças crônicas. Entre essas doenças estão: fibromialgia, migrânea crônica, síndrome do intestino irritável, síndrome dolorosa miofascial e síndrome de dor complexa regional. Frequentemente, várias dessas doenças se apresentam associadas. A terapia da dor nociplástica é um desafio na prática clínica, uma vez que a maioria dos tratamentos tradicionais não são eficazes no controle dos sintomas, causando muitas vezes dificuldade de adesão ou até mesmo interrupção do tratamento, devido aos efeitos adversos indesejáveis. O objetivo deste artigo foi demonstrar a importância da identificação da presença da dor nociplástica no quadro do paciente, e do conhecimento dos mecanismos fisiopatológicos envolvidos. Dessa forma, devido à neuromodulação retrógrada, característica exclusiva do sistema endocanabinoide até o momento, avaliar a utilização de fármacos de grau farmacêutico à base da planta cannabis como coadjuvante na terapia da dor e dos outros sintomas associados a essa doença.
CONTEÚDO: Este artigo abordou a fisiopatologia da dor nociplástica, a fisiologia do sistema endocanabinoide, a planta cannabis com seus componentes e sua utilização como medicação coadjuvante no tratamento multimodal da dor nociplástica (decorrente da neuromodulação retrógrada), com base em artigos científicos publicados entre 1981 e 2022.
CONCLUSÃO: Apesar das evidências científicas que apoiam o uso da cannabis medicinal na terapia da dor nociplástica serem insuficientes até o momento, ela pode e deve ser considerada como um possível fármaco coadjuvante na terapia multimodal da dor, sempre de forma individualizada, quando os tratamentos preconizados falharem ou não forem tolerados

Palavras-chave

Cannabis, Dor crônica, Dor nociplástica, Sistema endocanabinoide

References

1 IASP.2021.https://www.iasppain.org/Education/Content.aspx?ItemNumber=1698#-Nociplasticpain.

2 Kosek E, Cohen M, Baron R, Gebhart GF, Mico JA, Rice ASC, Rief W, Sluka AK. Do we need a third mechanistic descriptor for chronic pain states? Pain. 2016;157(7):1382-6.

3 Peres MF, Young WB, Kaup AO, Zukerman E, Silberstein SD. Fibromyalgia is common in patients with transformed migraine. Neurology. 200157(7):1326-8.

4 Yunus M, Masi AT, Calabro JJ, Miller KA, Feigenbaum SL. Primary fibromyalgia (fibrositis): clinical study of 50 patients with matched normal controls. Semin Arthritis Rheum. 1981;11(1):151-71.

5 Yunus MB. Fibromyalgia and overlapping disorders: the unifying concept of central sensitivity syndromes. Semin Arthritis Rheum. 2007;36(6):339-56.

6 Walitt B, Ceko M, Gracely JL, Gracely RH. Neuroimaging of central sensitivity syndromes: key insights from the scientific literature. Curr Rheumatol Rev. 2016;12(1):55-87.

7 Fitzcharles MA, Petzke F, Tölle TR, Häuser W. Cannabis-based medicines and medical cannabis in the treatment of nociplastic pain. Drugs. 2021;81(18):2103-16.

8 Toda, K. Are nociplastic pain and neuropathic pain different pains? Univ J Neurosci. 2022;1(1):1-2.

9 Leffler AS, Kosek E, Lerndal T, Nordmark B, Hansson P. Somatosensory perception and function of diffuse noxious inhibitory controls (DNIC) in patients suffering from rheumatoid arthritis. Eur J Pain. 2002;6(2):161-76.

10 Pollard LC, Ibrahim F, Choy EH, Scott DL. Pain thresholds in rheumatoid arthritis: the effect of tender point counts and disease duration. J Rheumatol. 2012;39(1):28-31.

11 Smallwood RF, Laird AR, Ramage AE, Parkinson AL, Lewis J, Clauw DJ, Williams DA, Schmidt-Wilcke T, Farrell MJ, Eickhoff SB, Robin DA. Structural brain anomalies and chronic pain: a quantitative meta-analysis of gray matter volume. J Pain. 2013;14(7):663-75.

12 Napadow V, Harris RE. What has functional connectivity and chemical neuroimaging in fibromyalgia taught us about the mechanisms and management of ‘centralized’ pain? Arthritis Res Ther. 2014;16(5):425.

13 Loggia ML, Kim J, Gollub RL, Vangel MG, Kirsch I, Kong J, Wasan AD, Napadow V. Default mode network connectivity encodes clinical pain: an arterial spin labeling study. Pain. 2013;154(1):24-33.

14 Ichesco E, Puiu T, Hampson JP, Kairys AE, Clauw DJ, Harte SE, Peltier SJ, Harris RE, Schmidt-Wilcke T. Altered fMRI resting-state connectivity in individuals with fibromyalgia on acute pain stimulation. Eur J Pain. 2016;20(7):1079-89.

15 Fleming KC, Volcheck MM. Central sensitization syndrome and the initial evaluation of a patient with fibromyalgia: a review. Rambam Maimonides Med J. 2015;6(2):e0020.

16 Fitzcharles MA, Cohen SP, Clauw DJ, Littlejohn G, Usui C, Häuser W. Nociplastic pain: towards an understanding of prevalent pain conditions. Lancet. 2021;397(10289):2098-110.

17 Lu HC, Mackie K. An introduction to the endogenous cannabinoid system. Biol Psychiatry. 2016;79(7):516-25.

18 Zou S, Kumar U. Cannabinoid receptors and the endocannabinoid system: signaling and function in the central nervous system. Int J Mol Sci. 2018;19(3):833.

19 Di Marzo, V, Piscitelli F. The endocannabinoid system and its modulation by phytocannabinoids. Neurotherapeutics. 2015;12(4):692-8.

20 Cravatt BF, Lichtman AH. The endogenous cannabinoid system and its role in nociceptive behavior. J Neurobiol. 2004;61(1):149-60.

21 Staud R. New evidence for central sensitization in patients with fibromyalgia. Curr Rheumatol Rep. 2004;6(4):259.

22 Bennett R. Fibromyalgia: present to future. Curr Pain Headache Rep. 2004;8(5):379-84.

23 Russo EB. Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Neuroendocrinol Lett. 2004;25(1):31-9.

24 Greco R, Gasperi V, Maccarrone M, Tassorelli C. The endocannabinoid system and migraine. Exp Neurol. 2010;224(1):85-91.

25 Sarchielli P, Pini LA, Coppola F, Rossi C, Baldi A, Mancini ML, Calabresi P. Endocannabinoids in chronic migraine: CSF findings suggest a system failure. Neuropsychopharmacology. 2007;32(6):1384-90.

26 Van Laere K, Casteels C, Dhollander I, Goffin K, Grachev I, Bormans G, Vandenberghe W. Widespread decrease of type 1 cannabinoid receptor availability in Huntington disease in vivo. J Nucl Med. 2010;51(9):1413-7.

27 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):154-65. doi: 10.1089/can.2016.0009.

28 van den Hoogen NJ, Harding EK, Davidson CED, Trang T. Cannabinoids in chronic pain: therapeutic potential through microglia modulation. Front Neural Circuits. 2022;15:816747.

29 Medeiros P, Oliveira-Silva M, Negrini-Ferrari SE, Medeiros AC, Elias-Filho DH, Coimbra NC, de Freitas RL. CB1-cannabinoid-, TRPV1-vanilloid- and NMDA-glutamatergic-receptor-signalling systems interact in the prelimbic cerebral cortex to control neuropathic pain symptoms. Brain Res Bull. 2020;165:118-28.

30 Hill KP, Palastro MD, Johnson B, Ditre JW. Cannabis and pain: a clinical review. Cannabis Cannabinoid Res. 2017;2(1):96-104.

31 Lago-Fernandez A, Zarzo-Arias S, Jagerovic N, Morales P. Relevance of peroxisome proliferator activated receptors in multitarget paradigm associated with the endocannabinoid system. Int J Mol Sci. 2021;22(3):1001.

32 Pascual D, Sánchez-Robles EM, García MM, Goicoechea C. Chronic pain and cannabinoids. Great expectations or a christmas carol. Biochem Pharmacol. 2018;157:33-42.

33 Al-Hasani R, Bruchas MR. Molecular mechanisms of opioid receptor-dependent signaling and behavior. Anesthesiology. 2011;115(6):1363-81.

34 Vučković S, Srebro D, Vujović KS, Vučetić Č, Prostran M. Cannabinoids and pain: new insights from old molecules. Front Pharmacol. 2018;9:1259.

35 Amin MR, Ali DW. Pharmacology of medical cannabis. Adv Exp Med Biol. 2019;1162:151-65.

36 McKenna M, McDougall JJ. Cannabinoid control of neurogenic inflammation. Br J Pharmacol. 2020;177(19):4386-99.

37 Feingold D, Rehm J, Lev-Ran S. Cannabis use and the course and outcome of major depressive disorder: a population based longitudinal study. Psychiatry Res. 2017;251:225-34.

38 Henderson LA, Kotsirilos V, Cairns EA, Ramachandran A, Peck CC, McGregor IS. Medicinal cannabis in the treatment of chronic pain. Aust J Gen Pract. 2021;50(10):724-32.

39 Alves P, Amaral C, Teixeira N, Correia-da-Silva G. Cannabis sativa: much more beyond Δ9-tetrahydrocannabinol. Pharmacol Res. 2020;157:104822.

40 Gulbransen G, Xu W, Arroll B. Cannabidiol prescription in clinical practice: An audit on the first 400 patients in New Zealand. BJGP Open 2020;4(1):bjgpopen20X101010.

41 Kalaba M, Ware MA. Cannabinoid profiles in medical cannabis users: effects of age, gender, symptoms, and duration of use. Cannabis Cannabinoid Res. 2022;7(6):840-51.

42 Bhaskar A, Bell A, Boivin M, Briques W, Brown M, Clarke H, Cyr C, Eisenberg E, de Oliveira Silva RF, Frohlich E, Georgius P, Hogg M, Horsted TI, MacCallum CA, Müller-Vahl KR, O’Connell C, Sealey R, Seibolt M, Sihota A, Smith BK, Sulak D, Vigano A, Moulin DE. Consensus recommendations on dosing and administration of medical cannabis to treat chronic pain: results of a modified Delphi process. J Cannabis Res. 2021;3(1):22.

43 Fitzcharles MA, Shir Y, Häuser W. Medical cannabis: strengthening evidence in the face of hype and public pressure. CMAJ. 2019;191(33):E907-E908.

44 Martin JH, Hall W, Fitzcharles MA, Borgelt L, Crippa J. Ensuring access to safe, effective, and affordable cannabis-based medicines. Br J Clin Pharmacol. 2020;86(4):630-4.
 


Submitted date:
03/28/2023

Accepted date:
04/28/2023

65553501a953952a46667264 brjp Articles

BrJP

Share this page
Page Sections