Characterization of the Cannabis Terpene Myrcene in Joint Pain and Inflammation in a Rat Model of Rheumatoid Arthritis

Abstract

Rheumatoid arthritis is a progressive inflammatory condition resulting in joint damage and debilitating pain. Current treatments present with variable efficacy and negative side effects, leaving pain management a priority. The endocannabinoid system has been targeted to relieve both inflammation and pain in disease conditions. Specifically, the non-euphoric cannabis terpene myrcene offers analgesic actions in acute pain models, and anti-inflammatory potential in vitro. We investigated the effect of both acute and chronic administration of myrcene alone, and in combination with cannabidiol, on pain and inflammation in the Freund’s complete adjuvant (FCA) rat model of rheumatoid arthritis. The involvement of the endocannabinoid system was also explored. Evoked and spontaneous pain behaviour were analyzed using von Frey hair algesiometry, dynamic weight bearing, and locomotor activity. Inflammatory parameters assessed were oedema, leukocyte trafficking, blood flow to the injured area, cytokine levels, and joint histopathology. Our study found that both acute and chronic administration of myrcene attenuated evoked mechanical allodynia, but did not improve FCA-induced weight bearing deficits, and did not alter locomotor activity. Acute administration of myrcene reduced leukocyte trafficking. Chronic administration reduced leukocyte trafficking and blood flow, yet had no effect on cytokine levels or disease progression. These anti-inflammatory effects were mediated via the endocannabinoid system; however, endocannabinoid-dependent analgesia was not confirmed. Excluding blood flow, the analgesic and anti-inflammatory effects of myrcene were comparable to diclofenac. The combination of myrcene with a suboptimal dose of cannabidiol did not enhance any of the above parameters. Compared to other analgesic treatments, myrcene may be a safer therapeutic to use in conjunction with disease-modifying treatments to adequately manage pain and inflammation in rheumatoid arthritis.