Abstract
The demonstrated expression of endocannabinoid receptors in myofascial tissue suggested the role of fascia as a source and modulator of pain. Fibroblasts can modulate the production of the various components of the extracellular matrix, according to type of stimuli: physical, mechanical, hormonal, and pharmacological. In this work, fascial fibroblasts were isolated from small samples of human fascia lata of the thigh, collected from three volunteer patients (two men, one woman) during orthopedic surgery. This text demonstrates for the first time that the agonist of cannabinoid receptor 2, HU-308, can lead to in vitro production of hyaluronan-rich vesicles only 3–4 h after treatment, being rapidly released into the extracellular environment. We demonstrated that these vesicles are rich in hyaluronan after Alcian blue and Toluidine blue stainings, immunocytochemistry, and transmission electron microscopy. In addition, incubation with the antagonist AM630 blocked vesicles production by cells, confirming that release of hyaluronan is a cannabinoid-mediated effect. These results may show how fascial cells respond to the endocannabinoid system by regulating and remodeling the formation of the extracellular matrix. This is a first step in our understanding of how therapeutic applications of cannabinoids to treat pain may also have a peripheral effect, altering the biosynthesis of the extracellular matrix in fasciae and, consequently, remodeling the tissue and its properties.
Highlights
Myofascial pain is a common clinical disorder, beginning as acute pain within the musculoskeletal system with a referred autonomic phenomenon, which includes pain, decreased ranged of motion, and weakness [1]
We demonstrated that these vesicles are rich in hyaluronan after Alcian blue and Toluidine blue stainings, immunocytochemistry, and transmission electron microscopy
This work demonstrates that a synthetic cannabinoid can lead to the production of hyaluronan and HA-rich vesicles in only a few hours in an in vitro culture of fascial fibroblasts
Summary
Myofascial pain is a common clinical disorder, beginning as acute pain within the musculoskeletal system with a referred autonomic phenomenon, which includes pain, decreased ranged of motion, and weakness [1]. In the United States over the last decade, there has been increasing availability and use of cannabis for medical purposes and it has become important to provide the public with accurate information as to the use and effectiveness of painkillers [9,10,11] For this reason, having already demonstrated in one of our previous works that the human fasciae express both endocannabinoid receptors CB1 and CB2 [12], we stimulated fascial cells with an agonist of CB2 receptors, to better understand the effects of these molecules in peripheral tissue; we confirmed the CB2-mediated effect blocking the action with a specific antagonist. We believe that the present work may improve our understanding of the effects of stimulation with a synthetic cannabinoid in peripheral tissue
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