Mandip Singh Sachdeva
Florida A&M University
Co-authors: Peggy Arthur1, Arvin Badge1, Anil Kumar Kalvala1
1Florida A&M University
Purpose: Chronic paclitaxel (PTX) treatment causes excruciating pain in cancer patients, limiting its use in cancer chemotherapy. Herein, neuroprotective potential of synthetic cannabidiol (CBD) and CBD formulated in extracellular vesicles (CBD-EVs) isolated from human umbilical cord derived mesenchymal stem cells were studied against PTXinduced neuropathic pain (PIPN) in C57BL/6J mice.
Methods: PTX (8 mg/kg, i.p,) was injected every other day (four doses) to induce neuropathy in C57BL/6J mice. CBD and CBD-EVs was administered (5 mg/kg, i.p) for 6 weeks with twice a week frequency. At the end of study, behavior of the animals towards pain perception were measured using Hargreaves plantar apparatus, hot and cold tail immersion test, vonfrey aesthesiometer and randalsellito apparatus. Dorsal root ganglions (DRGs) were isolated from animals for molecular studies. Further, invitro studies were conducted in DRG primary cultures to study the mitochondrial effects of CBD and CBD-EVs against PTX insult.
Results: EVs and CBD-EVs particle size, surface roughness, nanomechanical attributes, stability, and release studies were investigated. CBD-EVs treatment significantly improved mechanical and thermal hypersensitivity (P<0.001) as compared to EVs or CBD alone. PTXtreated mice’s dorsal root ganglions and spinal homogenates had mitochondrial dysfunction which was significantly improved by CBD and CBD-EVs by regulating the AMPK pathway (P<0.001). Blocking studies with 5HT1A receptors and AMPK demonstrated that CBD had no effect on PIPN neurobehavioral or mitochondrial function.
Conclusion: Our results suggest that CBD-EVs can be a novel therapeutic option for the treatment of PIPN and CBD treatment activates AMPK axis in regulating PIPN.