Effects of Cannabinoids Use in Temporomandibular Disorders: A Scoping ReviewABSTRACT
Objective: To assess the effects of cannabis and its synthetically derived products on temporomandibular disorders (TMD) treatment and explore the potential mechanisms underlying these effects in various TMD nociception models.
Material and Methods: Electronic searches in five databases were conducted for publications up to August 2024. Clinical and animal studies about the use of cannabinoids for TMD-related pain control were included. Letters to the editor, conference proceedings, protocol articles, historical reviews, in vitro studies, and unpublished articles were excluded.
Results: A total of 2,708 unique citations were found. Following the screening, 31 studies were evaluated as full-text copies, and 13 (nine pre-clinical, two observational, and two interventional studies) were included. The pre-clinical studies demonstrated that cannabinoid compounds effectively reduce nociceptive behavior in the temporomandibular joints (TMJ) and masseter muscle using different animal models. Moreover, all the included studies using formalin-induced TMJ nociception reported that cannabinoid agonist-induced antinociception in the TMJ region was mediated by the central activation of CB1 but not CB2 receptors. The observational and interventional studies reported pain reduction, improvement in function, and better health quality with cannabis use. Furthermore, the use of cannabis for chronic pain appears to be an effective alternative to the use of opioids and other pain control drugs associated with unwanted side effects.
Conclusion: The use of cannabis and its synthetically derived products seems to be effective in reducing nociceptive behavior in TMJ and masseter muscle. However, further clinical and mechanistic studies are necessary to thoroughly investigate the therapeutic potential of cannabinoid compounds in TMD.
Keywords:
Temporomandibular Joint Disorders; Cannabinoids; Masseter Muscle
Introduction
Temporomandibular disorders (TMD) encompass a group of dysfunctions and disorders affecting the temporomandibular joints (TMJ), masticatory musculature, and associated structures [1]. TMD is characterized by pain in the muscles of mastication, reduced mandibular range of motion, TMJ pain associated with joint noise with function, generalized myofascial pain, and a functional limitation or deviation of the jaw opening [2]. The TMD overall prevalence was approximately 31% for adults/elderly and 11% for children/adolescents [3], considered the second most common musculoskeletal condition associated with pain and disability.
According to the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD), TMD can be divided into pain and joint disorders [4]. Most pain disorders manifest as myofascial pain focused on the muscles of mastication [5]. Symptoms include chronic pain in the masticatory muscles and radiating pain to the ears, neck, and head [5]. Myofascial pain is associated with muscle strain, spasms, and functional limitations. The diagnosis of myofascial pain is based on the patient’s history and physical examination. Radiographic studies can also serve as supplemental diagnostic tools [5].
Therapy goals for myofascial patients focus on reducing pain and improving or restoring function [6].
Noninvasive modalities are often the first treatment option. Drug therapy is often prescribed as an adjunct for noninvasive or minimally invasive treatments to reduce pain and inflammation in the joints and/or muscles [6,7]. The drugs most commonly used are nonsteroidal anti-inflammatory drugs (NSAIDs), myorelaxants, corticosteroids, analgesics, benzodiazepines, and tricyclic antidepressants [6]. However, all these drugs are associated with adverse effects, as recently reviewed by Andre et al. [6], which can restrict the pharmacologic therapy prescription for myofascial pain management.
Cannabis sativa is a natural plant usually smoked or ingested for recreational purposes. This plant is commonly called cannabis. Recently, both natural cannabis and synthetic-derived products have been proposed for medical use in pain and inflammation management, particularly in cases where conventional treatments have proven ineffective [8]. Cannabis contains more than 565 chemical compounds, with over 100 classified as cannabinoids. The primary cannabinoids are D9-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN) [9]. THC is the main active component of cannabis, which provides psychoactive and analgesic properties [8]. CBD also affects pain control and exhibits anti-inflammatory properties [10].
In the human body, cannabinoids act on the endocannabinoid system through two cannabinoid receptors: CB1, primarily found in the central nervous system, but has also been found in many peripheral tissues, including trigeminal ganglion neurons, and CB2, which occurs mainly in the immune system [9]. Both receptors have been considered attractive therapeutic targets for pain management, as they induce pain relief in various models of nociceptive, inflammatory, and neuropathic pain [11]. In light of this, clinical [12] and pre-clinical studies [13] have investigated the effectiveness of cannabinoids in managing pain associated with TMD.
This scoping review was conducted to systematically map the research on the use of cannabinoids in TMD treatment and to identify any gaps in the current knowledge. It addresses the research question based on the PCC (population, concept, and context) criteria: Are cannabinoids effective in controlling TMD-related pain? Specifically, the review explores the effects of cannabis and its synthetic derivatives on TMD treatment and the potential mechanisms underlying these effects in various TMD nociception models.
Material and Methods
Protocol
This study was registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY) (registration number: INPLASY2024120087) and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR) guidelines [14].
Eligibility Criteria
The following inclusion criteria were adopted based on the following PCC criteria: (P) Population: patients/animals with TMD; (C) Concept: cannabinoids use; (C) Context: not applicable (the question does not reference cultural, geographical, or specific environmental factors). Clinical studies [including randomized clinical trials (RCTs), controlled clinical studies, cohort studies (prospective or retrospective), case series, and case reports) Furthermore, animal studies reporting data about the use of cannabinoids for TMD-related pain control were included. No language restriction was applied. Original research articles that did not follow the above criteria were excluded from this scoping review. Moreover, letters to the editor, conference proceedings, protocol articles, historical reviews, in vitro studies (cellular models), and unpublished articles were also excluded.
Information Sources and Search
Electronic searches of PubMed, EMBASE, Web of Science, Scopus, and Cochrane Library databases were conducted for publications up to August 2024. The search strategies were created using the Medical Subject Headings (MeSH) and Embase Subject Headings (Emtree). Boolean operators (AND and OR) combined the descriptors and improved the search strategy through different combinations, respecting each database syntax rule (Table S1 in supplementary materials). No filters were utilized in the search strategy.
The publications found in all electronic databases were transferred to the EndNote Program™ X9 version (Thomson Reuters, New York, NY, USA) to remove duplicate references. Then, the results were exported to Rayyan QCRI software (Qatar Computing Research Institute, Doha, Qatar) for selection by titles and abstracts. The reference lists of the identified articles were also hand-searched for additional studies.
Selection of Sources of Evidence
Two investigators (L.C.S. and C.F.B.) made the initial search for the evaluation of titles and abstracts independently using the previous eligibility criteria. Irrelevant studies were excluded, and the full text of the articles included based on title and abstract were independently read and evaluated according to selection criteria (L.C.S. and C.F.B.). Disagreements between reviewers were resolved by discussion, including a third investigator (D.A.F.A.) for the final decision. The articles excluded in the full-text analysis were listed separately, and the reasons for exclusion were specified.
Data Charting Process and Items
Two investigators (L.C.S. and C.F.B.) independently read all studies and extracted the following data for animal studies: (a) animal type, (b) TMD model, (c) experimental groups, (d) methods of pain evaluation, and (e) main outcomes. For clinical studies, the data extracted were: (a) study type; (b) patients’ number, gender, and mean age in each group; (c) medical history; (d) TMD treatment protocol; (e) methods of pain evaluation; (f) follow-up and (g) main outcomes. The extracted data were organized into a table created in Excel. After completing the data extraction, disagreements were discussed and resolved through consensus with the third reviewer (D.A.F.A.).
Synthesis of Results
Based on the review objective and question, a logical and descriptive summary of the results was made. The studies were categorized into in vivo and clinical groups. For in vivo studies, we summarized the study purpose, animal type, TMD model, experimental protocol, methods of pain evaluation, and main outcomes. The main outcomes for in vivo studies focused on the effects of cannabinoids in pain control using TMD models and the molecular mechanisms underlying this process. For clinical studies, we summarized the study type, purpose, participant numbers and demographics, medical history, TMD treatment protocol, pain evaluation methods, follow-up, and main outcomes. The main outcomes for clinical studies highlighted the clinical effects of cannabinoids in managing pain associated with TMD. All data were systematically organized into a table to provide a clear and concise overview of the evidence, facilitating the identification of trends, gaps, and variations across the included studies.
Results
Selection of Sources of Evidence
In the electronic search, 2,933 hits were found, with 2,708 unique citations. Following screening, 31 studies were evaluated as full-text copies, and 18 of these studies were excluded based on priori criteria (Figure 1). The exclusion motivation for each excluded study was shown in Table S2 in the supplementary materials. The remaining 13 studies (9 pre-clinical studies, two observational studies, and two interventional studies) were included in the scoping review.
Characteristics of Sources of Evidence
For in vivo studies (9 studies) (Table S3 in supplementary materials), the majority used rats (8 studies; 6 studies used male rats, and two studies used female rats), and only one study used mice. As the TMD experimental model, three studies used formalin-induced TMJ nociception [15,16,17], three studies used acute muscle pain (by hypertonic saline injection in the masseter) [18,19,20], two studies used Nerve growth factor (NGF)-induced sensitization in the masseter muscle [21,22], and one study used Complete Freund’s adjuvant (CFA) into the masseter muscle [13]. Four studies evaluated the WIN 55,212-2 compound (WIN), a synthetic non-subtype-selective cannabinoid CB1 and CB2 agonist [15,16,17,20]. Two studies evaluated the THC compound [18,21], two studies evaluated the CBD compound [13,22], one study evaluated the CBN compound [22], and one study evaluated the Cannabichromene (CBC) compound [22]. Regarding the pain evaluation methods, three studies evaluated the number of scratches and the duration of scratching [13,15,17]; three studies evaluated the total number of hind paw shakes [18,19,20]; two studies evaluated in vivo electrophysiology [21,22], and one study evaluated the face rubbing and head flinching [16].
The observational and interventional studies included (4 studies) (Table S4 in supplementary materials), two studies (1 cross-sectional study [23]), and 1 case series [24]) that used online questionnaires to evaluate medical cannabis use in chronic pain management. Patients with TMD were included in both studies. Two interventional studies [12,25] (classified as an RCT) evaluated the myorelaxant effect of CBD after transdermal or intraoral application in patients with myofascial pain.
Synthesis of Results
Pre-Clinical Studies
The studies included evaluating the effect of the cannabinoid agonist WIN 55,212-2 (WIN), which showed that the central activation of CB1 mediates cannabinoid-induced antinociception in the TMJ region but not CB2 receptors. On the other hand, Robles et al. [20] reported that both CB1 and CB2 receptors can reduce the nociceptive shaking behavior induced by hypertonic saline in the masseter muscle.
In addition, the central blockade of COX-2 pathways enhanced the antinociceptive effects mediated by the activation of the CB1 receptor, as reported by Ahn et al. [15]. However, intracisternal pretreatment with naloxone (opioid receptor antagonist) did not affect cannabinoid-induced antinociception. Similarly, Lee et al. [17] demonstrated that the central activation of a cannabinoid receptor enhances antinociception produced by intracisternal administered group II or III metabotropic glutamate receptors (mGluRs) agonists in the TMJ region. In Burgos et al. [16], WIN induced an antinociceptive effect in the TMJ region equivalent to morphine and superior to other analgesic drugs (indomethacin and ketamine). The studies also reported that intracisternal administration of WIN did not affect motor functions.
The THC antinociception effect was confirmed in two different models of muscle pain [18,21]. Moreover, no impairment of motor functions was reported after THC utilization [18,21]. However, contradictory results were reported regarding the CB1/CB2 receptor activation by THC. Bagues et al. [18] reported that when THC was administered systemically, its antinociceptive effect was antagonized by the selective CB1 cannabinoid antagonist in the masseter muscle. On the other hand, the CB2 receptor is responsible for the antinociceptive effect of THC after its local administration in the masseter muscle. In the study by Wong et al. [21], the THC was able to reverse the NGF-induced mechanical sensitization of muscle mechanoreceptors through the activation of CB1 receptors but not CB2 receptors.
Wanasuntronwong et al. [13] showed that the antinociceptive effects of CBD induced by acute orofacial nociception induced by CFA were mediated by vanilloid receptor 1 but not by calcitonin gene-related peptide (CGRP). In Wong and Cairns’s [22] study, intramuscular injections of non-psychoactive cannabinoids CBD and CBN and their combinations reversed NGF-induced sensitization in behavioral and electrophysiology experiments. A low concentration of CBD (1 mg/ml) enhanced the ability of CBN to reverse NGF-mechanical sensitization. In contrast, a higher concentration of CBD (5 mg/ml) appeared to decrease the effectiveness of CBN.
Observational and Interventional Studies
Both studies using online questionnaires applied in patients with chronic pain (including TMD) described that medical cannabis promoted pain reduction, improvement in function, and better health quality [23,24]. In the Boehnke et al. [23] study, the participants reported replacing opioids and other pain medications with medical cannabis due to improvement in symptom management and fewer adverse side effects. Similarly, Lynch et al. [24] reported that the majority of cannabis users were able to decrease the use of other medications associated with side effects. In addition, no serious adverse events associated with cannabis use were reported in this study, and patients reported that the benefits of using cannabis compensated for the side effects in every case.
In a parallel-group RCT, Nitecka-Buchta et al. [12] assessed CBD’s myorelaxant and antinociceptive effect after the transdermal application in patients with myofascial pain. The CBD oil was applied over the masseter muscle twice daily for up to 14 days. After 14 days, the CBD promoted a reduction in pain intensity of masseter muscles during resting position and improved muscle condition in patients with myofascial pain. Similarly, Walczynska-Dragon et al. [25] investigated the efficacy of CBD formulations at 5% and 10% in patients experiencing sleep bruxism and muscle-related TMDs. Patients with the higher CBD concentration (10%) experienced significant improvements in pain, muscle tension, and bruxism compared to the lower concentration (5%), while the placebo group showed minimal changes.
Discussion
The pre-clinical studies included in this scoping review demonstrated that cannabinoid compounds effectively reduce nociceptive behavior in TMJ and masseter muscle using different animal models. This effectiveness has been confirmed by observational [23,24] and interventional studies [12,25], which reported pain reduction, improved function, and better health quality with cannabis use. Moreover, the use of cannabis for chronic pain appears to be an effective alternative to the use of opioids and other pain control drugs associated with unwanted side effects.
Formalin-induced TMJ nociception was successfully utilized as a TMJ model of inflammatory pain to assess nociceptive and antinociceptive responses. Additionally, hypertonic saline injection in the masseter muscle was the most frequent model of acute muscle pain in the included studies. This experimental method has been widely adopted because the quality of the induced pain is comparable to clinical muscle pain with localized and referred pain [26,27]. On the other hand, two included studies also used NGF-induced sensitization in the masseter muscle [21,22] to mimic the tender points observed in the craniofacial regions of TMD patients [28,29]. Only one study reported using CFA to promote inflammatory processes in the masseter muscle [13]. CFA induces acute thermal and mechanical hypersensitivities for 1–2 h [21,30].
CB receptors belong to the family of G-protein coupled receptors, physiologically activated by endocannabinoids [31]. Both CB receptor subtypes lead to the inhibition of adenylate cyclase, which reduces the formation of the intracellular messenger substance cyclic adenosine monophosphate (cAMP) [12]. Both CB1 and CB2 receptors were expressed in trigeminal ganglion neurons innervating the masseter muscle, suggesting that these receptors can be targeted for masticatory muscle pain [21]. Robles et al. [20] reported that CB1 and CB2 receptors can reduce the nociceptive behavior promoted by hypertonic saline injection in the masseter muscle after WIN systemic and local administration.
On the other hand, all the included studies using formalin-induced TMJ nociception reported that the central activation of CB1 mediated WIN-induced antinociception in the TMJ region but not CB2 receptors [15,16,17]. These contradictory results can be associated with the different tests and tissues used (TMJ formalin test versus hypertonic saline injection in the masseter muscle). However, the innervation is trigeminal in all these cases [20].
For THC, Bagues et al. [18] demonstrated that the CB2 receptor seems responsible for the antinociceptive effect of local THC administration in the masseter muscle, and the CB1 receptor is associated with THC systemic administration. However, Wong et al. [21] showed that local THC administration was able to reverse the NGF-induced mechanical sensitization through the activation of CB1 receptors but not CB2 receptors. One potential explanation for the difference between both studies is that NGF-induced mechanical sensitization is not associated with significant tissue inflammation. Therefore, it might be expected that CB2 receptor activation (primarily expressed in immune cells) would have a limited effect in this model of myofascial pain sensitivity [21,32]. It is also important to highlight that the difference in the involvement of CB1 and CB2 receptors on the analgesic effect of WIN compound and THC can be explained by the differences between the pharmacodynamic and pharmacokinetic profiles of these compounds, as WIN is a synthetic compound and THC is a natural derivative of cannabis [33,34].
Vanilloid receptor 1 and CGRP are receptors in the peripheral ganglion that are crucial for sensory input modulation. However, Wanasuntronwong et al. [13] showed that the antinociceptive effects of CBD were mediated by vanilloid receptor 1 but not CGRP. It is suggested that cannabidiol is an agonist of vanilloid receptor 1, displacing capsaicin from vanilloid receptor 1 and increasing intracellular calcium levels in heterologous cells overexpressing vanilloid receptor 1 [35]. Therefore, continued binding of the cannabidiol–vanilloid receptor 1 complex might result in nociceptive sensitization [13].
The combined prescription of cannabinoids and other compounds to improve pain management has also been proposed for orofacial pain treatment [15,17]. Of particular note is the prescription of COX inhibitors, which promote analgesic effects by suppressing prostaglandin synthesis in the periphery [36]. As Ahn et al. [15] demonstrated, the central blockade of COX-2 pathways enhances the antinociceptive effects mediated by CB1 receptor activation in inflammation-induced TMJ nociception. This result emphasizes the therapeutic potential of combined administration of cannabinoids with COX inhibitors in TMD pharmacologic treatment. However, in the same study, it was demonstrated that the effects of cannabinoids to reduce inflammatory pain in the TMJ region do not involve crossover utilization of opioid receptor pathways. Likewise, Lee et al. [17] also showed the successful combination of sub-analgesic doses of group II or III mGluRs agonists with sub-analgesic doses of cannabinoids in treating TMJ-related inflammatory pain. The Group II and III mGluRs inhibit glutamate release through presynaptic autoreceptors at central synapses [37,38,39] and possibly interact with cannabinoid receptors in presynaptic terminals. According to the authors, combining both compounds ensures cannabinoid administrations at doses not associated with undesirable motor dysfunction [17].
The use of cannabinoids has significant central nervous system side effects, including immobility, catalepsy, or hypo-locomotion responses [40]. Moreover, the psychoactive effect of THC limits its use in clinical practice [12]. The local tissue administration of these drugs targeting peripheral receptors was proposed to address these effects as a treatment for TMD. All pre-clinical studies included in this scoping review demonstrated the efficacy of cannabinoid local administration using different models of nociceptive behavior in TMJ and masseter muscle. In line with these findings, Nitecka-Buchta et al. [12] showed that a 14-day extraoral application of a 1.46% CBD formulation led to a 70.2% reduction in patients’ pain and an 11 to 12.6% decrease in surface electromyography (sEMG) activity. This transdermal administration enabled a sustained drug release at the application site, minimizing adverse effects of higher systemic concentrations.
CBD’s polar chemical structure also enhances human skin absorption [41]. Conversely, Walczynska-Dragon et al. [25] found that patients using 10% CBD intraorally experienced a 57.4% reduction in pain and a 42.1% decrease in sEMG activity. While extraoral application yields more favorable outcomes for pain reduction, intraoral application shows more significant sEMG improvements and a notable reduction in sleep bruxism activity.
Considering that this scoping review had two main objectives: assessing the effects of cannabis and its synthetic derivatives on TMD treatment and investigating the potential mechanisms underlying these effects in various TMD nociception models, two significant limitations in the available literature should be noted. First, only two RCTs [12,25] were included, with limited sample sizes and follow-up periods, highlighting the need for further high-quality research to confirm the efficacy of topical CBD in managing myofascial pain. Additionally, although two observational studies included patients with TMD in their samples, they did not report individual results for this subgroup, making it difficult to extrapolate the findings to TMD patients. Furthermore, contradictory results were observed regarding the role of CB1 and CB2 receptors in managing masseter muscle pain. These limitations underscore the need for more robust and well-designed clinical trials to establish the therapeutic potential of cannabinoids in the pharmacological treatment of TMD.
Conclusion
The use of cannabis and its synthetically derived products appears to be effective in reducing nociceptive behavior in the TMJ and masseter muscle. Nonetheless, further clinical and mechanistic studies are necessary to investigate the therapeutic potential of cannabinoid compounds in TMD thoroughly.
Supplementary Material
The supplementary material for this paper is available on the website https://revista.uepb.edu.br/PBOCI/index, in PDF format, with free access.
-
Financial Support
We declare the support received by grants from the Foundation for Research Support of Minas Gerais (FAPEMIG), the Coordination for the Improvement of Higher Level or Education Personnel-Brazil (CAPES) – Finance Code 001, INCT Oral Health and Dentistry (Process number: 406840/2022-9) and Rede Mineira em Saúde Oral e Odontologia (Process number: RED-00204-23).
Data Availability
The data used to support the findings of this study can be made available upon request to the corresponding author.
References
-
1 Okeson JP, de Leeuw R. Differential diagnosis of temporomandibular disorders and other orofacial pain disorders. Dent Clin North Am 2011; 55(1):105-120. https://doi.org/10.1016/j.cden.2010.08.007
» https://doi.org/10.1016/j.cden.2010.08.007 - 2 Wadhwa S, Kapila S. TMJ disorders: Future innovations in diagnostics and therapeutics. J Dent Educ 2008; 72(8):930-947.
-
3 Valesan LF, Da-Cas CD, Reus JC, Denardin ACS, Garanhani RR, Bonotto D, et al. Prevalence of temporomandibular joint disorders: A systematic review and meta-analysis. Clin Oral Investig 2021; 25(2):441-453. https://doi.org/10.1007/s00784-020-03710-w
» https://doi.org/10.1007/s00784-020-03710-w -
4 Schiffman E, Ohrbach R, Truelove E, Look J, Anderson G, Goulet JP, et al. Diagnostic criteria for Temporomandibular Disorders (DC/TMD) for clinical and research applications: Recommendations of the International RDC/TMD Consortium Network* and Orofacial Pain Special Interest Group† J Oral Facial Pain Headache 2014; 28(1):6-27. https://doi.org/10.11607/jop.1151
» https://doi.org/10.11607/jop.1151 -
5 Liu F, Steinkeler A. Epidemiology, diagnosis, and treatment of temporomandibular disorders. Dent Clin North Am 2013; 57(3):465-479. https://doi.org/10.1016/j.cden.2013.04.006
» https://doi.org/10.1016/j.cden.2013.04.006 -
6 Andre A, Kang J, Dym H. Pharmacologic treatment for temporomandibular and temporomandibular joint disorders. Oral Maxillofac Surg Clin North Am 2022; 34(1):49-59. https://doi.org/10.1016/j.coms.2021.08.001
» https://doi.org/10.1016/j.coms.2021.08.001 -
7 Wieckiewicz M, Boening K, Wiland P, Shiau YY, Paradowska-Stolarz A. Reported concepts for the treatment modalities and pain management of temporomandibular disorders. J Headache Pain 2015; 16:106. https://doi.org/10.1186/s10194-015-0586-5
» https://doi.org/10.1186/s10194-015-0586-5 -
8 Grossman S, Tan H, Gadiwalla Y. Cannabis and orofacial pain: A systematic review. Br J Oral Maxillofac Surg 2022; 60(5):e677-e690. https://doi.org/10.1016/j.bjoms.2021.06.005
» https://doi.org/10.1016/j.bjoms.2021.06.005 -
9 Laursen L. Botany: The cultivation of weed. Nature 2015; 525(7570):S4-5. https://doi.org/10.1038/525S4a
» https://doi.org/10.1038/525S4a -
10 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(3):Cd012182. https://doi.org/10.1002/14651858.CD012182.pub2
» https://doi.org/10.1002/14651858.CD012182.pub2 -
11 Karst M, Wippermann S, Ahrens J. Role of cannabinoids in the treatment of pain and (painful) spasticity. Drugs 2010; 70(18):2409-2438. https://doi.org/10.2165/11585260-000000000-00000
» https://doi.org/10.2165/11585260-000000000-00000 -
12 Nitecka-Buchta A, Nowak-Wachol A, Wachol K, Walczyńska-Dragon K, Olczyk P, Batoryna O, et al. Myorelaxant effect of transdermal cannabidiol application in patients with TMD: A randomized, double-blind trial. J Clin Med 2019; 8(11):1886. https://doi.org/10.3390/jcm8111886
» https://doi.org/10.3390/jcm8111886 -
13 Wanasuntronwong A, Kaewsrisung S, Rotpenpian N, Arayapisit T, Pavasant P, Supronsinchai W. Efficacy and mechanism of the antinociceptive effects of cannabidiol on acute orofacial nociception induced by Complete Freund’s Adjuvant in male Mus musculus mice. Archives of oral biology 2022; 144:105570. https://doi.org/10.1016/j.archoralbio.2022.105570
» https://doi.org/10.1016/j.archoralbio.2022.105570 -
14 Tricco AC, Lillie E, Zarin W, O’Brien KK, Colquhoun H, Levac D, et al. PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and explanation. Ann Intern Med 2018; 169(7):467-473. https://doi.org/10.7326/m18-0850
» https://doi.org/10.7326/m18-0850 -
15 Ahn DK, Choi HS, Yeo SP, Woo YW, Lee MK, Yang GY, et al. Blockade of central cyclooxygenase (COX) pathways enhances the cannabinoid-induced antinociceptive effects on inflammatory temporomandibular joint (TMJ) nociception. Pain 2007; 132(1):23-32. https://doi.org/10.1016/j.pain.2007.01.015
» https://doi.org/10.1016/j.pain.2007.01.015 -
16 Burgos E, Pascual D, Martín MI, Goicoechea C. Antinociceptive effect of the cannabinoid agonist, WIN 55,212-2, in the orofacial and temporomandibular formalin tests. Eur J Pain 2010; 14(1):40-48. https://doi.org/10.1016/j.ejpain.2009.02.003
» https://doi.org/10.1016/j.ejpain.2009.02.003 -
17 Lee MK, Choi BY, Yang GY, Jeon HJ, Kyung HM, Kwon OW, et al. Low doses of cannabinoids enhance the antinociceptive effects of intracisternally administered mGluRs groups II and III agonists in formalin-induced TMJ nociception in rats. Pain 2008; 139(2):367-375. https://doi.org/10.1016/j.pain.2008.05.005
» https://doi.org/10.1016/j.pain.2008.05.005 -
18 Bagues A, Martin MI, Sanchez-Robles EM. Involvement of central and peripheral cannabinoid receptors on antinociceptive effect of tetrahydrocannabinol in muscle pain. Eur J Pharmacol 2014; 745:69-75. https://doi.org/10.1016/j.ejphar.2014.10.016
» https://doi.org/10.1016/j.ejphar.2014.10.016 -
19 Cumella J, Hernández-Folgado L, Girón R, Sánchez E, Morales P, Hurst DP, et al. Chromenopyrazoles: Non-psychoactive and selective CB₁ cannabinoid agonists with peripheral antinociceptive properties. ChemMedChem 2012; 7(3):452-463. https://doi.org/10.1002/cmdc.201100568
» https://doi.org/10.1002/cmdc.201100568 -
20 Robles EMS, Arias AB, Fontelles MIM. Cannabinoids and muscular pain. Effectiveness of the local administration in rat. European Journal of Pain 2012; 16(8):1116-1127. https://doi.org/10.1002/j.1532-2149.2012.00115.x
» https://doi.org/10.1002/j.1532-2149.2012.00115.x -
21 Wong H, Hossain S, Cairns BE. Delta-9-tetrahydrocannabinol decreases masticatory muscle sensitization in female rats through peripheral cannabinoid receptor activation. Eur J Pain 2017; 21(10):1732-1742. https://doi.org/10.1002/ejp.1085
» https://doi.org/10.1002/ejp.1085 -
22 Wong H, Cairns BE. Cannabidiol, cannabinol and their combinations act as peripheral analgesics in a rat model of myofascial pain. Arch Oral Biol 2019; 104:33-39. https://doi.org/10.1016/j.archoralbio.2019.05.028
» https://doi.org/10.1016/j.archoralbio.2019.05.028 -
23 Boehnke KF, Scott JR, Litinas E, Sisley S, Williams DA, Clauw DJ. Pills to pot: Observational analyses of cannabis substitution among medical cannabis users with chronic pain. J Pain 2019; 20(7):830-841. https://doi.org/10.1016/j.jpain.2019.01.010
» https://doi.org/10.1016/j.jpain.2019.01.010 -
24 Lynch ME, Young J, Clark AJ. A case series of patients using medicinal marihuana for management of chronic pain under the Canadian Marihuana Medical Access Regulations. J Pain Symptom Manage 2006; 32(5):497-501. https://doi.org/10.1016/j.jpainsymman.2006.05.016
» https://doi.org/10.1016/j.jpainsymman.2006.05.016 -
25 Walczynska-Dragon K, Kurek-Gorecka A, Niemczyk W, Nowak Z, Baron S, Olczyk P, et al. Cannabidiol intervention for muscular tension, pain, and sleep bruxism intensity-A randomized, double-blind clinical trial. J Clin Med 2024; 13(5):1417. https://doi.org/10.3390/jcm13051417
» https://doi.org/10.3390/jcm13051417 -
26 Svensson P. What can human experimental pain models teach us about clinical TMD? Arch Oral Biol 2007; 52(4):391-394. https://doi.org/10.1016/j.archoralbio.2006.11.015
» https://doi.org/10.1016/j.archoralbio.2006.11.015 -
27 Capra NF, Ro JY. Human and animal experimental models of acute and chronic muscle pain: Intramuscular algesic injection. Pain 2004; 110(1-2):3-7. https://doi.org/10.1016/j.pain.2004.04.033
» https://doi.org/10.1016/j.pain.2004.04.033 -
28 Wong H, Dong XD, Cairns BE. Nerve growth factor alters the sensitivity of rat masseter muscle mechanoreceptors to NMDA receptor activation. J Neurophysiol 2014; 112(9):2275-2282. https://doi.org/10.1152/jn.00327.2014
» https://doi.org/10.1152/jn.00327.2014 -
29 Wong H, Kang I, Dong XD, Christidis N, Ernberg M, Svensson P, et al. NGF-induced mechanical sensitization of the masseter muscle is mediated through peripheral NMDA receptors. Neuroscience 2014; 269:232-244. https://doi.org/10.1016/j.neuroscience.2014.03.054
» https://doi.org/10.1016/j.neuroscience.2014.03.054 -
30 Kopach O, Viatchenko-Karpinski V, Belan P, Voitenko N. Development of inflammation-induced hyperalgesia and allodynia is associated with the upregulation of extrasynaptic AMPA receptors in tonically firing lamina II dorsal horn neurons. Front Physiol 2012; 3:391. https://doi.org/10.3389/fphys.2012.00391
» https://doi.org/10.3389/fphys.2012.00391 -
31 Müller CE. Fortschritte in der Cannabis-Forschung aus pharmazeutisch-chemischer Sicht. Bundesgesundheitsbl 2019; 62(7):818-824. https://doi.org/10.1007/s00103-019-02964-4 [In German].
» https://doi.org/10.1007/s00103-019-02964-4 - 32 Mann MK, Dong XD, Svensson P, Cairns BE. Influence of intramuscular nerve growth factor injection on the response properties of rat masseter muscle afferent fibers. J Orofac Pain 2006; 20(4):325-336.
-
33 Svízenská I, Dubový P, Sulcová A. Cannabinoid receptors 1 and 2 (CB1 and CB2), their distribution, ligands and functional involvement in nervous system structures--A short review. Pharmacol Biochem Behav 2008; 90(4):501-511. https://doi.org/10.1016/j.pbb.2008.05.010
» https://doi.org/10.1016/j.pbb.2008.05.010 -
34 Howlett AC, Barth F, Bonner TI, Cabral G, Casellas P, Devane WA, et al. International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev 2002; 54(2):161-202. https://doi.org/10.1124/pr.54.2.161
» https://doi.org/10.1124/pr.54.2.161 -
35 Bisogno T, Hanus L, De Petrocellis L, Tchilibon S, Ponde DE, Brandi I, et al. Molecular targets for cannabidiol and its synthetic analogues: Effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br J Pharmacol 2001; 134(4):845-852. https://doi.org/10.1038/sj.bjp.0704327
» https://doi.org/10.1038/sj.bjp.0704327 -
36 Vinegar R, Truax JF, Selph JL, Welch RM, White HL, Ellis CH. Potentiation of the anti-inflammatory and analgesic activity of aspirin by caffeine in the rat. Proc Soc Exp Biol Med 1976; 151(3):556-560. https://doi.org/10.3181/00379727-151-39257
» https://doi.org/10.3181/00379727-151-39257 -
37 Anwyl R. Metabotropic glutamate receptors: electrophysiological properties and role in plasticity. Brain Res Brain Res Rev 1999; 29(1):83-120. https://doi.org/10.1016/s0165-0173(98)00050-2
» https://doi.org/10.1016/s0165-0173(98)00050-2 -
38 Conn PJ, Pin JP. Pharmacology and functions of metabotropic glutamate receptors. Annu Rev Pharmacol Toxicol 1997; 37:205-237. https://doi.org/10.1146/annurev.pharmtox.37.1.205
» https://doi.org/10.1146/annurev.pharmtox.37.1.205 -
39 Doherty J, Dingledine R. Functional interactions between cannabinoid and metabotropic glutamate receptors in the central nervous system. Curr Opin Pharmacol 2003; 3(1):46-53. https://doi.org/10.1016/s1471-4892(02)00014-0
» https://doi.org/10.1016/s1471-4892(02)00014-0 -
40 Romero-Sandoval EA, Asbill S, Paige CA, Byrd-Glover K. Peripherally restricted cannabinoids for the treatment of pain. Pharmacotherapy 2015; 35(10):917-925. https://doi.org/10.1002/phar.1642
» https://doi.org/10.1002/phar.1642 -
41 Coffey RG, Yamamoto Y, Snella E, Pross S. Tetrahydrocannabinol inhibition of macrophage nitric oxide production. Biochem Pharmacol 1996; 52(5):743-751. https://doi.org/10.1016/0006-2952(96)00356-5
» https://doi.org/10.1016/0006-2952(96)00356-5
Edited by
-
Academic Editor:
Alessandro Leite Cavalcanti
