Females have greater susceptibility to develop ongoing pain and central sensitization in a rat model of temporomandibular joint pain

Abstract

Temporomandibular joint osteoarthritis (TMJOA) is a prevalent source of temporomandibular joint disorder (TMD). Women are more commonly diagnosed with TMD and are more likely to seek care at tertiary orofacial pain clinics. Limited knowledge regarding mechanisms underlying temporomandibular joint (TMJ) pain impairs development of improved pain management strategies. In a rat model of unilateral TMJOA, monosodium iodoacetate (MIA) produces joint pathology in a concentration-dependent manner. Unilateral MIA produces alterations in meal patterns in males and females without altering overnight time spent eating or weight across 2 weeks. Monosodium iodoacetate (80 mg/mL)-treated males develop ongoing pain within 2 weeks after MIA injection. Females develop ongoing pain at a 5-fold lower MIA concentration (16.6 mg/m). Monosodium iodoacetate (80 mg/mL)-treated males show spread of tactile hypersensitivity across the face during the first week after injection and then to the fore paws and hind paws during the second week after injection, indicating development of central sensitization. At the lower dose, female rats demonstrate a similar spread of tactile hypersensitivity, whereas male rats do not develop ongoing pain or spread of tactile hypersensitivity outside the area of the ipsilateral temporomandibular joint. These observations indicate that females have a higher susceptibility to development of ongoing pain and central sensitization compared with male rats that is not due to differences in MIA-induced joint pathology. This model of TMJOA pain can be used to explore sex differences in pain processes implicated in development of neuropathic pain, ongoing pain, and central sensitization, allowing for development of individualized strategies for prevention and treatment of TMD joint pain.

Enhanced post-traumatic headache-like behaviors and diminished contribution of peripheral CGRP in female rats following a mild closed head injury

“…Female sex has been suggested as a key positive predictor for development of PTH (33–35) and has been attributed to their higher prevalence of pre-existing headache and migraine (33,34). Given that our rats did not encounter any potential headache producing event prior to the mCHI, our findings rather point to other/additional mechanisms, potentially related to increased nociceptive processing at the level of the peripheral and/or the central nervous system in females (14,36–38), in particular facilitation of the process underlying the development of trigeminal central sensitization in response to head trauma.…”

Gender Differences in Clinical Characteristics of Korean Temporomandibular Disorder Patients

“…Secondly, for the genetic factors that can contribute to pain perception, proinflammatory cytokines and extracellular matrix breakdown may affect the female predilection [55]. Thirdly, the psychosocial factors that contain an enhanced response to stress stimuli, distress, anxiety, depression, or reduced coping strategies have been reported to make gender differences [56][57][58][59].…”

Is Irritable Bowel Syndrome Considered in Clinical Trials on Physical Therapy Applied to Patients with Temporo-Mandibular Disorders? A Scoping Review

“…Finally, 80% of the patients with TMD included in the clinical trials were female, which may be related to the fact that TMD is more prevalent in females than in males and also that a greater frequency of comorbidity in pain syndromes and TMDs is present in females [ 68 ]. Since women exhibit greater susceptibility of developing central sensitivity syndromes [ 72 ], future clinical trials investigating the effects of physical therapy interventions for the management of TMDs should consider potential gender differences in their eligibility criteria.…”