PMID- 38293066 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240131 DP - 2024 Jan 16 TI - Forced mouth opening induces post-traumatic hyperalgesia and associated peripheral sensitization after temporomandibular joints injury in mice. LID - 2024.01.16.575891 [pii] LID - 10.1101/2024.01.16.575891 [doi] AB - Temporomandibular disorder (TMD) is the most prevalent painful condition in the craniofacial area. The pathophysiology of TMD is not fully understood, and it is necessary to understand pathophysiology underlying painful TMD conditions to develop more effective treatment methods. Recent studies suggested that external or intrinsic trauma to TMJ is associated with chronic TMD in patients. Here, we investigated the effects of the TMJ trauma through forced-mouth opening (FMO) in mice to determine pain behaviors and peripheral sensitization of trigeminal nociceptors. FMO increased mechanical hyperalgesia assessed by von Frey test, spontaneous pain-like behaviors assessed by mouse grimace scale, and anxiety-like behaviors assessed by open-field test. In vivo GCaMP Ca (2+) imaging of intact trigeminal ganglia (TG) showed increased spontaneous Ca (2+) activity and mechanical hypersensitivity of TG neurons in the FMO compared to the sham group. Ca (2+) responses evoked by cold, heat, and capsaicin stimuli were also increased. FMO-induced hyperalgesia and neuronal hyperactivities were not sex dependent. TG neurons sensitized following FMO were primarily small to medium-sized nociceptive afferents. Consistently, most TMJ afferents in the TG were small-sized peptidergic neurons expressing calcitonin gene-related peptides, whereas nonpeptidergic TMJ afferents were relatively low. FMO-induced intraneural inflammation in the surrounding tissues of the TMJ indicates potentially novel mechanisms of peripheral sensitization following TMJ injury. These results suggest that the TMJ injury leads to persistent post-traumatic hyperalgesia associated with peripheral sensitization of trigeminal nociceptors. FAU - Alshanqiti, Ishraq AU - Alshanqiti I FAU - Son, Hyeonwi AU - Son H FAU - Shannonhouse, John AU - Shannonhouse J FAU - Hu, Jiaxin AU - Hu J FAU - Kumari, Sinu AU - Kumari S FAU - Parastooei, Ghazaal AU - Parastooei G FAU - Wang, Sheng AU - Wang S FAU - Ro, Jin Y AU - Ro JY FAU - Kim, Yu Shin AU - Kim YS FAU - Chung, Man-Kyo AU - Chung MK LA - eng PT - Preprint DEP - 20240116 PL - United States TA - bioRxiv JT - bioRxiv : the preprint server for biology JID - 101680187 PMC - PMC10827102 EDAT- 2024/01/31 06:43 MHDA- 2024/01/31 06:44 PMCR- 2024/01/30 CRDT- 2024/01/31 04:19 PHST- 2024/01/31 06:44 [medline] PHST- 2024/01/31 06:43 [pubmed] PHST- 2024/01/31 04:19 [entrez] PHST- 2024/01/30 00:00 [pmc-release] AID - 2024.01.16.575891 [pii] AID - 10.1101/2024.01.16.575891 [doi] PST - epublish SO - bioRxiv [Preprint]. 2024 Jan 16:2024.01.16.575891. doi: 10.1101/2024.01.16.575891.