Delta‐9‐tetrahydrocannabinol decreases masticatory muscle sensitization in female rats through peripheral cannabinoid receptor activation

Abstract

Background: 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. Methods: 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. Results: 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 lL) of THC (1 mg/mL) 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. Conclusions: 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. Significance: 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.

Fast Blue and Cholera Toxin-B Survival Guide for Alpha-Motoneurons Labeling: Less Is Better in Young B6SJL Mice, but More Is Better in Aged C57Bl/J Mice

“…In intramuscular injection studies that utilize rodents such as ours, the standard concentration at which FB has been used is mostly 2% [48,63]. Interestingly, our results show that a 0.2% FB protocol-a much lower concentration than what has been used before and 10-fold lower than the standard concentration-has comparable labeling quality in young mice (see Figure 1), while in aged mice, 2% was clearly better (Figures 7 and 8).…”

“…Because of the absence of this knowledge, sub-optimal protocols and high tracer concentrations continue to be used in various studies ranging from injecting tracers into muscle, nerves, and other locations of the rodents' body to labeling α-MNs and other various types of neurons. For instance, in the last seven years only, at least 13 studies have used FB concentrations (>1.5%, and as high as 5%) [38][39][40][41][42][43][44][45][46][47][48][49][50][51] while only 6 studies have used low FB concentrations (<1.5%) [52][53][54][55][56]. This indicates that low FB concentrations (i.e., <1%) are still not popular, and their advantages over high concentrations are still unknown despite having been used for a long time [57][58][59].…”

Phytocannabinoids: General Aspects and Pharmacological Potential in Neurodegenerative Diseases

“…Activation of CB1-R by THC ( 13, Fig. 3 ) also causes local analgesia [ 83 , 84 ] when intramuscularly injected at the dose of 1mg/mL, and without adverse effects [ 84 ].…”

Myorelaxant Effect of Transdermal Cannabidiol Application in Patients with TMD: A Randomized, Double-Blind Trial

“…Both CB receptor subtypes lead to inhibition of adenylate cyclase and thus to reduced formation of the intracellular messenger substance cyclic adenosine monophosphate (cAMP). CB 1 receptors are activated by THC and CBD and are responsible for the local analgesic effect [22]. The chemical structure of THC and CBD is slightly different, resulting in a different mechanism of action (Figure 1).…”