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Evaluation of cannabis constituents in preventing or reversing phantom limb pain in rats

Kristin Perrucci
University of Miami

Co-Authors: Anjalika Eeswara1, Vama Shah1, Stanislava Jergova1, Jacqueline Sagen1
1University of Miami

Phantom Limb Pain (PLP) arising from a missing limb affects up to 85% of amputees. One of the most frequently reported uses of medical marijuana is for pain relief. CB constituents such as delta-9-tetrahydrocannabinol (THC), Cannabidiol (CBD) and β-caryophyllene (BCP) may be beneficial for managing complex chronic pain syndromes like PLP due to their distinct and possibly synergistic mechanisms. The goal of this study was to evaluate the combined analgesic potential of these compounds in preventing or reversing PLP-like behavior. To model complex extremity injuries leading to medically-indicated amputation, male Sprague-Dawley rats underwent chronic constriction injury (CCI) of the sciatic nerve (day 0) and intraplantar formalin, followed by complete axotomy of the sciatic nerve (day 7). CB dosing was initiated either immediately following transection or at the start of PLP symptoms to evaluate whether CB treatment could prevent or reverse PLP, respectively. To assess for PLP, animals were observed daily using a scale designed to capture autotomy severity. Animals were injected twice daily with either CBD:BCP, CBD:BCP:THC, THC or vehicle with doses based on other studies in our lab showing good analgesia without side effects. Animals were sacrificed when proximal injury appeared or at the 10 wk study end and tissues were evaluated for inflammatory cytokines and spinal pathology. In both the prevention and reversal dosing scenario, all administered CB combinations attenuated the severity and onset of PLP symptoms compared to vehicle controls. When treatment was initiated immediately, either THC alone or CBD:BCP combination reduced autotomy scores more than the full CBD:BCP:THC. However, when treatment was initiated following the onset of PLP symptoms, the full complement of CBD:BCP:THC was most effective in reducing PLP behavior. Effective CB treatment combinations were found to significantly upregulate anti-inflammatory cytokines IL-4 and IL-10 and restore inhibitory GABAergic function in lumbar spinal tissue. These results suggest that cannabis constituents, CBD, BCP and THC, when used in combination have the potential to both prevent PLP symptoms from occurring and reverse the course of PLP severity development. These findings further substantiate the use of cannabis constituents as therapeutic agents for the management of neuropathic pain.

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