scholarly journals Potential for endocannabinoid system modulation in ocular pain and inflammation: filling the gaps in current pharmacological options

2018 ◽  
Vol 2 (4) ◽  
Author(s):  
J. Daniel Lafreniere ◽  
Melanie E.M. Kelly
Keyword(s):  
Chronic Pain ◽  
Current Knowledge ◽  
Endocannabinoid System ◽  
Ocular Pain ◽  
Physiological Basis ◽  
Future Directions ◽  
Anti Inflammatory ◽  
Neuroprotective Actions ◽  
Chronic Pain Conditions ◽  
Ocular Safety

Challenges in the management of ocular pain are an underappreciated topic. Currently available therapeutics lack both efficacy and clear guidelines for their use, with many also possessing unacceptable side effects. Promising novel agents would offer analgesic, anti-inflammatory, and possibly neuroprotective actions; have favorable ocular safety profiles; and show potential in managing neuropathic pain. Growing evidence supports a link between the endocannabinoid system (ECS) and a range of physiological and disease processes, notably those involving inflammation and pain. Both preclinical and clinical data suggest analgesic and anti-inflammatory actions of cannabinoids and ECS-modifying drugs in chronic pain conditions, including those of neuropathic origin. This review will examine existing evidence for the anatomical and physiological basis of ocular pain, specifically, ocular surface disease and the development of chronic ocular pain. The mechanism of action, efficacy, and limitations of currently available treatments will be discussed, and current knowledge related to ECS-modulation of ocular pain and inflammatory disease will be summarized. A perspective will be provided on the future directions of ECS research in terms of developing cannabinoid therapeutics for ocular pain.

Cannabinoids in the management of chronic pain: a front line clinical perspective

2016 ◽  
Vol 27 (3) ◽  
Author(s):  
Mary E. Lynch
Keyword(s):  
Chronic Pain ◽  
Analgesic Effect ◽  
Endocannabinoid System ◽  
Public Health Problem ◽  
Immune Defense ◽  
Preclinical Research ◽  
Novel Treatments ◽  
New Frontier ◽  
Excellent Work ◽  
Chronic Pain Conditions

AbstractChronic pain is an escalating public health problem. Currently available treatments are inadequate to control chronic pain conditions, and there is a critical need for novel treatments. Over a half century of elegant preclinical research has identified the presence of a sophisticated endocannabinoid system that is part of our natural pain and immune defense network. Convergent work has supported the significant potential to exploit this system to decrease pain and inflammation. Although the clinical research remains in its infancy, recent systematic reviews have found that 25 of 30 randomized controlled trials have demonstrated a significant analgesic effect. The authors concluded that cannabinoids currently available for clinical use demonstrate a modest analgesic effect and are safe for the management of chronic pain. There is a critical need for more translational research so that the excellent work of Dr. Itai Bab and our basic science colleagues around the world can move forward in providing novel cannabinoid-based medicines. This should include more potent analgesics that are limited in side effects with several routes of delivery. Our patients deserve additional agents for pain control with a novel mechanism of action, and cannabinoids are the new frontier.

scholarly journals Inherent Sex Differences in the Expression of the Endocannabinoid System within V1M Cortex and PAG of Sprague Dawley Rats

2021 ◽  
Author(s):  
Aidan Levine ◽  
Erika Liktor-Busa ◽  
Austin A Lipinski ◽  
Sarah Couture ◽  
Shreya Balasubramanian ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Chronic Pain ◽  
Sex Differences ◽  
Cannabinoid Receptors ◽  
Endocannabinoid System ◽  
Brain Regions ◽  
Sprague Dawley ◽  
Female Population ◽  
Sprague Dawley Rats ◽  
Chronic Pain Conditions

Abstract Background: Several chronic pain disorders, such as migraine and fibromyalgia, have an increased prevalence in the female population. The underlying mechanisms of this sex-biased prevalence have yet to be thoroughly documented but could be related to endogenous differences in neuromodulators in pain networks, including the endocannabinoid system. The cellular endocannabinoid system is comprised of the endogenous lipid signals 2-AG (2-arachidonoylglycerol) and AEA (anandamide); the enzymes that synthesize and degrade them; and the cannabinoid receptors. The relative prevalence of different components of the endocannabinoid system in specific brain regions may alter responses to endogenous and exogenous ligands. Methods: Brain tissue from naïve male and female Sprague Dawley rats was harvested from V1M cortex, periaqueductal gray, trigeminal nerve, and trigeminal nucleus caudalis. Tissue was analyzed for relative levels of endocannabinoid enzymes, ligands, and receptors via mass spectrometry, unbiased proteomic analysis, and immunohistochemistry. Results: Mass spectrometry revealed cortical AEA levels were significantly higher in males compared to females (p<0.001), whereas 2-AG levels in periaqueductal grey were significantly higher in females compared to males (p<0.0001). Immunohistochemistry followed by unbiased proteomics confirmed the prevalence of 2-AG-endocannabinoid system enzymes in the female PAG.Conclusions: Our results suggest that sex differences exist in the endocannabinoid system in two CNS regions relevant to cortical spreading depression (V1M cortex) and descending modulatory networks in pain/anxiety (PAG). These basal differences in endogenous endocannabinoid mechanisms may facilitate the development of chronic pain conditions and may also underlie sex differences in response to therapeutic intervention.

scholarly journals Sex differences in the expression of the endocannabinoid system within V1M cortex and PAG of Sprague Dawley rats

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Aidan Levine ◽  
Erika Liktor-Busa ◽  
Austin A. Lipinski ◽  
Sarah Couture ◽  
Shreya Balasubramanian ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Chronic Pain ◽  
Sex Differences ◽  
Cannabinoid Receptors ◽  
Endocannabinoid System ◽  
Brain Regions ◽  
Sprague Dawley ◽  
Female Population ◽  
Sprague Dawley Rats ◽  
Chronic Pain Conditions

Abstract Background Several chronic pain disorders, such as migraine and fibromyalgia, have an increased prevalence in the female population. The underlying mechanisms of this sex-biased prevalence have yet to be thoroughly documented, but could be related to endogenous differences in neuromodulators in pain networks, including the endocannabinoid system. The cellular endocannabinoid system comprises the endogenous lipid signals 2-AG (2-arachidonoylglycerol) and AEA (anandamide); the enzymes that synthesize and degrade them; and the cannabinoid receptors. The relative prevalence of different components of the endocannabinoid system in specific brain regions may alter responses to endogenous and exogenous ligands. Methods Brain tissue from naïve male and estrous staged female Sprague Dawley rats was harvested from V1M cortex, periaqueductal gray, trigeminal nerve, and trigeminal nucleus caudalis. Tissue was analyzed for relative levels of endocannabinoid enzymes, ligands, and receptors via mass spectrometry, unlabeled quantitative proteomic analysis, and immunohistochemistry. Results Mass spectrometry revealed significant differences in 2-AG and AEA concentrations between males and females, as well as between female estrous cycle stages. Specifically, 2-AG concentration was lower within female PAG as compared to male PAG (*p = 0.0077); female 2-AG concentration within the PAG did not demonstrate estrous stage dependence. Immunohistochemistry followed by proteomics confirmed the prevalence of 2-AG-endocannabinoid system enzymes in the female PAG. Conclusions Our results suggest that sex differences exist in the endocannabinoid system in two CNS regions relevant to cortical spreading depression (V1M cortex) and descending modulatory networks in pain/anxiety (PAG). These basal differences in endogenous endocannabinoid mechanisms may facilitate the development of chronic pain conditions and may also underlie sex differences in response to therapeutic intervention.

scholarly journals Leptin and Associated Mediators of Immunometabolic Signaling: Novel Molecular Outcome Measures for Neurostimulation to Treat Chronic Pain

2019 ◽  
Vol 20 (19) ◽  
pp. 4737 ◽  
Author(s):  
Thomas Kinfe ◽  
Michael Buchfelder ◽  
Shafqat Chaudhry ◽  
Krishnan Chakravarthy ◽  
Timothy Deer ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Large Scale ◽  
Metabolic Disorders ◽  
Current Knowledge ◽  
Experimental Studies ◽  
Clinical Value ◽  
Failed Back Surgery ◽  
Electrical Neuromodulation ◽  
Chronic Pain Conditions ◽  
Cellular Components

Chronic pain is a devastating condition affecting the physical, psychological, and socioeconomic status of the patient. Inflammation and immunometabolism play roles in the pathophysiology of chronic pain disorders. Electrical neuromodulation approaches have shown a meaningful success in otherwise drug-resistant chronic pain conditions, including failed back surgery, neuropathic pain, and migraine. A literature review (PubMed, MEDLINE/OVID, SCOPUS, and manual searches of the bibliographies of known primary and review articles) was performed using the following search terms: chronic pain disorders, systemic inflammation, immunometabolism, prediction, biomarkers, metabolic disorders, and neuromodulation for chronic pain. Experimental studies indicate a relationship between the development and maintenance of chronic pain conditions and a deteriorated immunometabolic state mediated by circulating cytokines, chemokines, and cellular components. A few uncontrolled in-human studies found increased levels of pro-inflammatory cytokines known to drive metabolic disorders in chronic pain patients undergoing neurostimulation therapies. In this narrative review, we summarize the current knowledge and possible relationships of available neurostimulation therapies for chronic pain with mediators of central and peripheral neuroinflammation and immunometabolism on a molecular level. However, to address the needs for predictive factors and biomarkers, large-scale databank driven clinical trials are needed to determine the clinical value of molecular profiling.

scholarly journals Medical cannabis for orthopaedic patients with chronic musculoskeletal pain: does evidence support its use?

2020 ◽  
Vol 12 ◽  
pp. 1759720X2093796
Author(s):  
Herman Johal ◽  
Christopher Vannabouathong ◽  
Yaping Chang ◽  
Meng Zhu ◽  
Mohit Bhandari
Keyword(s):  
Chronic Pain ◽  
Musculoskeletal Pain ◽  
Endocannabinoid System ◽  
Current Evidence ◽  
Therapeutic Effects ◽  
Current Guideline ◽  
Medical Cannabis ◽  
Orthopaedic Patients ◽  
Effectiveness Factors ◽  
Chronic Pain Conditions

The treatment of chronic, non-cancer musculoskeletal pain has become a topic growing interest as it is believed to be one of the reasons for the current opioid epidemic. The medicinal use of cannabis has a long history as a number of active compounds in cannabis have been shown to interact with the body’s endocannabinoid system to reduce pain. This position paper provides a history on the evolution of cannabis, the science behind its therapeutic effects, and review of the evidence and current guideline recommendations on its use as a treatment for patients with chronic, non-cancer musculoskeletal pain. Results from systematic reviews have demonstrated a statistically significant reduction in chronic pain conditions with cannabinoids, compared with placebo, although the effects might be considered small and did not reach the minimally important difference. More adverse events were reported in the cannabinoid group than in the placebo group with longer than 2 weeks of treatment. There is a lack of evidence on dependence. With changes to policies, patients’ perception has changed to be more positive toward the use of medical cannabis. Current recommendations from North America, Latin America, Europe, Australia and Iran support the use of medical cannabis for chronic, non-cancer pain. Based on the current evidence, it is our position that cannabinoids may be considered as an adjunctive therapy after recommended first- and second-line therapies have failed to provide sufficient efficacy or tolerability. Patients should consider the balance between the desirable and undesirable effects of taking cannabis for chronic pain, and comprehensively consider their own values and preferences, as well as cost-effectiveness factors, based on the information provided by their physician.

Free Fatty Acid Receptors as New Potential Targets in Colorectal Cancer

2020 ◽  
Vol 21 (14) ◽  
pp. 1397-1404
Author(s):  
Adrian Bartoszek ◽  
Jakub Fichna ◽  
Aleksandra Tarasiuk ◽  
Agata Binienda ◽  
Adam Fabisiak ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Current Knowledge ◽  
Developed Countries ◽  
Future Directions ◽  
Screening Programs ◽  
Pharmacological Targets ◽  
The Family ◽  
Free Fatty Acid Receptors

Colorectal cancer (CRC) is one of the most common cancers worldwide. In developed countries, its mortality remains high, yet the prevalence has established owing to effective screening programs; however due to the westernization of lifestyle, the incidences in many other countries have increased. Although the treatment of CRC has improved in the last few years, the side effects of these approaches cannot be neglected. Recently, members of the family of free fatty acid receptors (FFARs) have become attractive pharmacological targets in many diseases, including asthma; studies also point to their role in carcinogenesis. Here, we discuss current knowledge and future directions in FFAR research related to CRC. Contradictory results of FFARs modulation may derive from the pleiotropic effects of FFAR ligands, receptor distribution and different signal transduction. Hence, we indicate directions of further studies to fully use the potential of FFARs in CRC.

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