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Delta-9-tetrahydrocannabinol decreases masticatory muscle sensitization in female rats through peripheral cannabinoid receptor activation.
Eur J Pain. 2017 11; 21(10):1732-1742.EJ

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 μL) 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.

Authors+Show Affiliations

Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada.InMed Pharmaceuticals Inc., Vancouver, BC, Canada.Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28722246

Citation

Wong, H, et al. "Delta-9-tetrahydrocannabinol Decreases Masticatory Muscle Sensitization in Female Rats Through Peripheral Cannabinoid Receptor Activation." European Journal of Pain (London, England), vol. 21, no. 10, 2017, pp. 1732-1742.
Wong H, Hossain S, Cairns BE. Delta-9-tetrahydrocannabinol decreases masticatory muscle sensitization in female rats through peripheral cannabinoid receptor activation. Eur J Pain. 2017;21(10):1732-1742.
Wong, H., Hossain, S., & Cairns, B. E. (2017). Delta-9-tetrahydrocannabinol decreases masticatory muscle sensitization in female rats through peripheral cannabinoid receptor activation. European Journal of Pain (London, England), 21(10), 1732-1742. https://doi.org/10.1002/ejp.1085
Wong H, Hossain S, Cairns BE. Delta-9-tetrahydrocannabinol Decreases Masticatory Muscle Sensitization in Female Rats Through Peripheral Cannabinoid Receptor Activation. Eur J Pain. 2017;21(10):1732-1742. PubMed PMID: 28722246.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Delta-9-tetrahydrocannabinol decreases masticatory muscle sensitization in female rats through peripheral cannabinoid receptor activation. AU - Wong,H, AU - Hossain,S, AU - Cairns,B E, Y1 - 2017/07/18/ PY - 2017/06/21/accepted PY - 2017/7/20/pubmed PY - 2018/5/17/medline PY - 2017/7/20/entrez SP - 1732 EP - 1742 JF - European journal of pain (London, England) JO - Eur J Pain VL - 21 IS - 10 N2 - 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 μL) 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. SN - 1532-2149 UR - https://www.unboundmedicine.com/medline/citation/28722246/Delta_9_tetrahydrocannabinol_decreases_masticatory_muscle_sensitization_in_female_rats_through_peripheral_cannabinoid_receptor_activation_ L2 - https://doi.org/10.1002/ejp.1085 DB - PRIME DP - Unbound Medicine ER -