Activation of type II cannabinoid receptors as variant for mesenchymal stem cell potentiation in a model of peripheral neuropathic pain

Abstract

Transplantation  of  adipose-derived  mesenchymal  stem  cells  (ADMSCs)  is  currently considered as one of the treatment methods of peripheral neuropathic pain. The analgesic effect of ADMSCs has been proven, and one of the potential options for its enhancement and prolongation could be the activation of type 2 cannabinoid receptors (CB2 receptors). The antinociceptive and reparative effects of ADMSCs were analyzed after type 2 cannabinoid receptors (CB2) pharmacological stimulation by the selective agonist AM1241 on the ADMSC’s membranes and in the tissues of the area of sciatic nerve traumatic injury in rats. It was found that  pharmacological  stimulation  of  CB2  receptors  on  ADMSC’s  membranes  accelerated the  recovery  of  nociceptive  sensitivity  to  mechanical  and  thermal  stimuli  compared  with transplantation of ADMSCs alone. Early (before transplantation of ADMSCs) activation of CB2 receptors in tissues surrounding the sciatic nerve more effectively attenuated nociceptive responses to thermal stimuli in the long-term period of the experiment. Stimulation of CB2 receptors did not significantly affect the rate of recovery of gait parameters in rats after ADMSCs transplantation, but led to the structure recovery of the sciatic nerve distal segment of rats. The latter was expressed in increased proliferation of Schwann cells and a decrease in the number of damaged nerve fibers.