The management of visceral pain in patients with disorders of gut-brain interaction, notably irritable bowel syndrome, presents a considerable clinical challenge, with few available treatment options. Patients are increasingly using cannabis and cannabinoids to control abdominal pain. Cannabis acts on receptors of the endocannabinoid system, an endogenous system of lipid mediators that regulates gastrointestinal function and pain processing pathways in health and disease. The endocannabinoid system represents a logical molecular therapeutic target for the treatment of pain in irritable bowel syndrome. Here, we review the physiological and pathophysiological functions of the endocannabinoid system with a focus on the peripheral and central regulation of gastrointestinal function and visceral nociception. We address the use of cannabinoids in pain management, comparing them to other treatment modalities, including opioids and neuromodulators. Finally, we discuss emerging therapeutic candidates targeting the endocannabinoid system for the treatment of pain in irritable bowel syndrome.
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http://dx.doi.org/10.1038/s41575-022-00682-y | DOI Listing |
Front Pharmacol
January 2025
Pharmacology and Therapeutics, School of Medicine, University of Galway, Galway, Ireland.
Paclitaxel (PTX) is a commonly used chemotherapeutic drug, however, one of its major adverse effects is chronic neuropathic pain, with the incidence being higher in women than in men. The neurobiological mechanisms behind this sex difference are still largely unclear, and the endocannabinoid system, which exhibits sexual dimorphism and plays a key role in pain regulation, is a promising area for further studies. The present study aimed to characterise pain-, cognition-, anxiety-, and depression-related behaviours in male and female rats following PTX administration, and associated alterations in the endocannabinoid system.
View Article and Find Full Text PDFNeuromodulatory signaling is poised to serve as a neural mechanism for gain control, acting as a crucial tuning factor to influence neuronal activity by dynamically shaping excitatory and inhibitory fast neurotransmission. The endocannabinoid (eCB) signaling system, the most widely expressed neuromodulatory system in the mammalian brain, is known to filter excitatory and inhibitory inputs through retrograde, pre-synaptic action. However, whether eCBs exert retrograde gain control to ultimately facilitate reward-seeking behaviors in freely moving mammals is not established.
View Article and Find Full Text PDFPharmacol Ther
January 2025
Xi'an Key Laboratory for Antiviral and Antimicrobial-Resistant Bacteria Therapeutics Research, Shaanxi University of Science & Technology, Xi'an 710021, China; School of Biological and Pharmaceutical Sciences, Shaanxi University of Science & Technology, Xi'an 710021, China. Electronic address:
G protein-coupled receptors (GPCRs) adopt conformational states that activate or inhibit distinct signaling pathways, including those mediated by G proteins or β-arrestins. Biased signaling through GPCRs may offer a promising strategy to enhance therapeutic efficacy while reducing adverse effects. Cannabinoid receptor 1 (CB1), a key GPCR in the endocannabinoid system, presents therapeutic potential for conditions such as pain, anxiety, cognitive impairment, psychiatric disorders, and metabolic diseases.
View Article and Find Full Text PDFJ Physiol
January 2025
College of Medicine, Department of Pharmacology, University of Arizona, Tucson, AZ, USA.
The endocannabinoid system's significance in maintaining blood-brain barrier (BBB) integrity under physiological and pathological conditions is suggested by several reports, but the underlying molecular mechanisms are not well understood. In this paper, we investigated the effects of depletion of 2-arachidonoylglycerol (2-AG), one of the main endocannabinoids in the central nervous system, on BBB integrity using pharmacological tools. Female Sprague-Dawley rats were injected with the diacylglycerol lipase α (DAGLα) inhibitor LEI-106 (40 mg/kg, i.
View Article and Find Full Text PDFTissue Eng Regen Med
January 2025
Department of Plastic Surgery, Hand Surgery-Burn Center, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany.
Background: Because of its biocompatibility and its soft and dynamic nature, the grafting of adipose tissue is regarded an ideal technique for soft-tissue repair. The adipose stem cells (ASCs) contribute significantly to the regenerative potential of adipose tissue, because they can differentiate into adipocytes and release growth factors for tissue repair and neovascularization to facilitate tissue survival. The present study tested the effect of administering a chronic low dose of ∆-tetrahydrocannabinol (THC) on these regenerative properties, in vitro and in vivo.
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