Delta-9-tetrahydrocannabinol decreases masticatory muscle sensitization in female rats through peripheral cannabinoid receptor activation.
This study investigated whether intramuscular injection of delta-9-tetrahydrocannabinol (THC), by acting on peripheral cannabinoid (CB) receptors, could decrease nerve growth factor (NGF)-induced sensitization in female rat masseter muscle a model which mimics the symptoms of myofascial temporomandibular disorders. Immunohistochemistry was used to explore the peripheral expression of cannabinoid receptors in the masseter muscle while behavioural and electrophysiology experiments were employed to assess the functional effects of intramuscular injection of THC. It was found that CB1 and CB2 receptors are expressed by trigeminal ganglion neurons that innervate the masseter muscle and also on their peripheral endings. Their expression was greater in TRPV1-positive ganglion neurons. Three days after intramuscular injection of NGF, ganglion neuron expression of CB1 and CB2, but not TPRV1, was decreased. In behavioural experiments, intramuscular injection (10 μL) of THC (1 mgmL) attenuated NGF-induced mechanical sensitization. No change in mechanical threshold was observed in the contralateral masseter muscles and no impairment of motor function was found after intramuscular injections of THC. In anaesthetized rats, the same concentration of THC increased the mechanical thresholds of masseter muscle mechanoreceptors. Co-administration of the CB1 antagonist AM251 blocked the effect of THC on masseter muscle mechanoreceptors while the CB2 antagonist AM630 had no effect. These results suggest that reduced inhibitory input from the peripheral cannabinoid system may contribute to NGF-induced local myofascial sensitization of mechanoreceptors. Peripheral application of THC may counter this effect by activating the CB1 receptors on masseter muscle mechanoreceptors to provide analgesic relief without central side effects. Our results suggest THC could reduce masticatory muscle pain through activating peripheral CB1 receptors. Peripheral application of cannabinoids could be a novel approach to provide analgesic relief without central side effects.