Spontaneous and Bite-Evoked Muscle Pain Are Mediated by a Common Nociceptive Pathway With Differential Contribution by TRPV1

Abstract

Spontaneous pain and function-associated pain are prevalent symptoms of multiple acute and chronic muscle pathologies. We established mouse models for evaluating spontaneous pain and bite-evoked pain from masseter muscle, and determined the roles of TRPV1 and the contribution of TRPV1- or NK1-dependent nociceptive pathways. Masseter muscle inflammation increased mouse grimace scale (MGS) scores and face wiping behavior which were attenuated by pharmacological or genetic inhibition of TRPV1. Masseter inflammation led to a significant reduction in bite force. Inhibition of TRPV1 only marginally relieved the inflammation-induced reduction of bite force. These results suggest differential extent of contribution of TRPV1 to the two types of muscle pain. However, chemical ablation of TRPV1-expressing nociceptors or chemogenetic silencing of TRPV1-lineage nerve terminals in masseter muscle attenuated inflammation-induced changes in both MGS scores and bite force. Furthermore, ablation of neurons expressing neurokinin 1 (NK1) receptor in trigeminal subnucleus caudalis also prevented both types of muscle pain. Our results suggest that TRPV1 differentially contribute to spontaneous pain and bite-evoked muscle pain, but TRPV1-expressing afferents and NK1-expressing second order neurons commonly mediate both types of muscle pain. Therefore, manipulation of the nociceptive circuit may provide a novel approach for management of acute or chronic craniofacial muscle pain.

Nociceptive behavioural assessments in mouse models of temporomandibular joint disorders

“…15,35 However, TMDs may also affect other tissues, in addition to the TMJ, such as orofacial muscles and nerves, which could also lead to mastication dysfunction. [16][17][18][19][20] Therefore, reduced bite force and changes in chewing behaviour might also reflect dysfunction of the jaw muscles and periodontal tissues, [21][22][23][24] which requires further investigation. Indeed, alterations in bite force and eating behaviours might not be entirely attributable to TMD-associated changes in nociceptive behaviours.…”

Peripheral glutamate receptor and transient receptor potential channel mechanisms of craniofacial muscle pain

“…Supporting this notion, chemical ablation of TRPV1-expressing primary afferents using resiniferatoxin injected into Vc or chemogenetic inhibition of TRPV1-lineage masseter afferent terminals attenuates both development of spontaneous pain and reduction in bite force following masseter inflammation. 65 Furthermore, ablation of neurokinin1 receptorexpressing projection neurons in Vc also produces the same effects. In contrast to the inhibitory effects of ablating TRPV1-expressing afferents, the inhibition of TRPV1 molecules only modestly reversed decreased bite force following CFA injection into masseter muscle and the inhibition of TRPA1 did not affect bite force at all.…”

The search for translational pain outcomes to refine analgesic development: Where did we come from and where are we going?

“…Facial expressions were found to be reliable pain indicators under several circumstances, including pain induced by chemical irritants in somatic tissues or visceral organs (Langford et al, 2010;Sotocinal et al, 2011;Kim et al, 2015a;Hassan et al, 2017;Herrera et al, 2018), inflammation (e.g. Langford et al, 2010;Sotocinal et al, 2011;De Rantere et al, 2016;Wang et al, 2017 and2018), migraine models (Harris et al, 2017;Rea et al, 2018;), spinal cord injury (Schneider et al, 2017;Chaves et al, 2018), and different types of postsurgical pain, e.g. after laparotomy (Langford et al, 2010;Sotocinal et al, 2011;Matsumiya et al, 2012;Kendall et al, 2016;Tuttle et al, 2018), laminectomy (Chaves et al, 2018), castration, or vasectomy (Miller et al, 2016;Dalla Costa et al, 2018).…”