Systematic review and meta-analysis of cannabinoids, cannabis-based medicines, and endocannabinoid system modulators tested for antinociceptive effects in animal models of injury-related or pathological persistent pain

Soliman, Nadia; Haroutounian, Simon; Hohmann, Andrea G.; Krane, Elliot J.; Liao, Jing; Macleod, Malcolm; Segelcke, Daniel; Sena, Christopher; Thomas, James; Vollert, Jan; Wever, Kimberley E.; Alaverdyan, Harutyun; Barakat, Ahmed; Barthlow, Tyler; Bozer, Amber L. Harris; Davidson, Alexander; Diaz‐delCastillo, Marta; Dolgorukova, Antonina; Ferdousi, Mehnaz; Healy, Catherine; Hong, Simon; Hopkins, Mary Ann; James, Alexandra; Leake, Hayley B.; Malewicz, Nathalie M.; Mansfield, Michael; Mardon, Amelia K.; Mattimoe, Darragh; McLoone, Daniel P; Noes-Holt, Gith; Pogatzki-Zahn, Esther; Power, Emer; Pradier, Bruno; Romanos‐Sirakis, Eleny; Segelcke, Astra; Vinagre, Rafael; Yanes, Julio A.; Zhang, Jingwen; Zhang, Xue Ying; Finn, David P.; Rice, Andrew S.C.

doi:10.1097/j.pain.0000000000002269

Cited by 95 publications

(113 citation statements)

References 62 publications

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“…The analgesic effects of cannabinoids are well established in preclinical models of pain 13 and arise primarily via interactions with the endocannabinoid system (ECS). The ECS is a ubiquitous system with multiple functions and comprises lipid signalling molecules called endocannabinoids (eg anandamide and 2-arachydonyl glycerol ) that bind to specific cannabinoid receptors (CB1 and CB2 receptors) or other endocannabinoidsensitive receptors (eg GPR18, GPR55, GPR119, TRPA1, TRPV1).…”

Section: Hiv Human Immunodeficiency Virusmentioning

confidence: 99%

“…Inhibition of FAAH leads to elevated systemic endocannabinoid concentrations and analgesic effects in animal models of pain. 13 In humans, a recent case study describes an elderly woman with a genetic polymorphism that reduces FAAH expression leading to elevated endocannabinoid concentrations and pain insensitivity. 14 Reduced FAAH function is also associated with reduced need for postoperative analgesia in women undergoing breast cancer surgery.…”

Section: Hiv Human Immunodeficiency Virusmentioning

confidence: 99%

“…The role of CB2 receptors in mediating THC effects and in analgesia is not entirely clear; effects of CB2 receptor agonists on inflammation-induced pain are better described than their effects on nerve injury-related pain. 13 Notably, a CB2 receptor-preferring agonist, lenabasum, is currently in late-stage clinical trials for the treatment of various inflammatory autoimmune conditions and fibrosis. 19 CBD, in contrast to THC, does not directly activate CB1 receptors, and this explains its absence of intoxicating effects.…”

Section: Phytocannabinoidsmentioning

confidence: 99%

“…20 CBD interacts, however, with a range of ECS-related receptors, and enzymes, to produce an array of anticonvulsant, anxiolytic, antipsychotic, anti-inflammatory and possible analgesic effects. 21 While CBD appears analgesic in animal models, particularly those modelling neuropathic pain, 13 there are minimal data related to analgesic effects in humans.…”

Section: Phytocannabinoidsmentioning

confidence: 99%

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Medicinal cannabis in the treatment of chronic pain

Henderson¹,

Kotsirilos²,

Cairns³

et al. 2021

Aust J Gen Pract

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BackgroundChronic pain is a major health issue, adversely affecting millions of Australians and costing billions of dollars annually. Current pharmaceutical treatments may be limiting, and in some cases ineffective, while carrying substantial liabilities. Medicinal cannabis is an increasingly popular, albeit controversial, alternative. Medicinal cannabis in the treatment of chronic painMedicinal cannabis in the treatment of chronic pain Clinical

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Section: Hiv Human Immunodeficiency Virusmentioning

confidence: 99%

Section: Hiv Human Immunodeficiency Virusmentioning

confidence: 99%

Section: Phytocannabinoidsmentioning

confidence: 99%

Section: Phytocannabinoidsmentioning

confidence: 99%

See 2 more Smart Citations

Medicinal cannabis in the treatment of chronic pain

Henderson¹,

Kotsirilos²,

Cairns³

et al. 2021

Aust J Gen Pract

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“…From a historical perspective, evoked pain-related behaviors are assessed by determining withdrawal reactions to external applied mechanical and thermal stimuli to the hindpaw of rodents. However, these assessments [still used in most preclinical pain studies (2,4,5)] are not only prone to experimental bias (6); they also encompass mainly the somatosensory (spinal reflex) pathways and miss the complex cognitive and emotional as well as voluntary components of pain. In contrast, multidimensional behavioral outcome measures in preclinical settings presumably capturing clinically relevant symptoms might improve translation (1,(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Investigating the Role of Ly6G+ Neutrophils in Incisional and Inflammatory Pain by Multidimensional Pain-Related Behavioral Assessments: Bridging the Translational Gap

et al. 2021

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In recent years, preclinical pain research has failed to develop genuinely new analgesics for clinical use. This fact is reflected by a high number of patients, limited drug efficacy accompanied by side effects, and a long-term opioid intake. Two main aspects have been addressed, which hinder translation: the use of non-relevant pain models and a mismatch between pain-related outcomes in preclinical and clinical studies. Conversely, disease-specific pain models that mirror more closely the clinical situation and multidimensional behavioral outcome measures that objectively and reproducibly assess relevant pain-related symptoms in a preclinical setting could improve translation. Mechanistically, a matter of debate is the role of Ly6G+ neutrophil granulocytes (NGs) for pain. NGs are essential to eliminate pathogens and promote the wound healing process. For this purpose, there is a need to release various pro- and anti-inflammatory mediators, some of which could ameliorate or enhance pain. However, the contribution of NGs to different pain entities is contradictory for reflex-based tests, and completely unknown in the context of non-evoked pain (NEP) and movement-evoked pain (MEP). First, we combined withdrawal reflex-based assays with novel video-based assessments for NEP- and MEP-related behavior in two mouse pain models. The pain models utilized in this study were incision (INC) and pathogen/adjuvant-induced inflammation (CFA), translating well to postsurgical and inflammatory pain entities. Second, we depleted NGs and applied a set of behavioral assessments to investigate the role of NG migration in different pain modalities. Our comprehensive behavioral approach identified pain-related behaviors in mice that resemble (NEP) or differentiate (MEP) behavioral trajectories in comparison to mechanical and heat hypersensitivity, thereby indicating modality-dependent mechanisms. Further, we show that injury-induced accumulation of NGs minimally affects pain-related behaviors in both pain models. In conclusion, we report a novel assessment to detect NEP in mice after unilateral injuries using a more unbiased approach. Additionally, we are capable of detecting an antalgic gait for both pain entities with unique trajectories. The different trajectories between MEP and other pain modalities suggest that the underlying mechanisms differ. We further conclude that NGs play a subordinate role in pain-related behaviors in incisional and inflammatory pain.

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The Association Between Employment in Coal Mining and History of Injury, Current Pain, and Prescription Opioid Use

Friedman,

Go,

Dang

et al. 2024

American J Industrial Med

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BackgroundCoal mining involves heavy physical demand, which is associated with increased risk of injury and long‐term musculoskeletal health disorders and chronic pain. Management of chronic or recurrent pain is in turn associated with prescription opioid use and risk of opioid use disorder (OUD).MethodsWe analyzed clinical data from 5463 coal miners evaluated between 2004 and 2015. Using an iterative text mining procedure, we analyzed structured clinical notes to extract information on occupational histories and clinical data. We evaluated associations along the causal chain using a series of multivariable logistic regression models to determine the relationship between (1) specific mining occupations and history of traumatic injury, (2) history of traumatic injury and current pain, and (3) current pain and current prescription opioid use.ResultsAmong these mostly‐former coal miners (mean age 62.4 years), the average coal mining tenure was 27.3 years; 88.4% reported being previously injured, 92.3% reported suffering from current pain and 39.2% reported current prescription opioid use. Occupations involving the most strenuous mining work were associated with a history of traumatic injury. A history of traumatic injury to body regions of the head/neck/back/spine was associated with current pain involving the head/neck/back/spine (adjusted OR = 5.04; CI 95%: 4.46, 5.70; p < 0.001). In a separate model, reported current pain of the head/neck/back/spine was associated with current prescription opioid use (aOR = 2.66; CI 95%: 2.35, 3.01; p < 0.001).ConclusionsThese miners had a high prevalence of self‐reported current pain, and certain specific mining occupations were more strongly associated with a history of injury, pain, and prescription opioid use.

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Systematic review and meta-analysis of cannabinoids, cannabis-based medicines, and endocannabinoid system modulators tested for antinociceptive effects in animal models of injury-related or pathological persistent pain

Abstract: Supplemental Digital Content is Available in the Text.

Cited by 95 publications

References 62 publications

Medicinal cannabis in the treatment of chronic pain

Medicinal cannabis in the treatment of chronic pain

Investigating the Role of Ly6G+ Neutrophils in Incisional and Inflammatory Pain by Multidimensional Pain-Related Behavioral Assessments: Bridging the Translational Gap

The Association Between Employment in Coal Mining and History of Injury, Current Pain, and Prescription Opioid Use

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