A clinically relevant animal model of temporomandibular disorder and irritable bowel syndrome comorbidity

Abstract

Temporomandibular disorder and irritable bowel syndrome are comorbid functional chronic pain disorders of unknown etiology that are triggered/exacerbated by stress. Here we present baseline phenotypic characterization of a novel animal model to gain insight into the underlying mechanisms that contribute to such comorbid pain conditions. In this model, chronic visceral hypersensitivity, a defining symptom of irritable bowel syndrome, is dependent on 3 factors: estradiol, existing chronic somatic pain, and stress. In ovariectomized rats, estradiol replacement followed by craniofacial muscle injury and stress induced visceral hypersensitivity that persisted for months. Omission of any 1 factor resulted in a transient (1 week) visceral hypersensitivity from stress alone or no hypersensitivity (no inflammation or estradiol). Maintenance of visceral hypersensitivity was estradiol dependent, resolving when estradiol replacement ceased. Referred cutaneous hypersensitivity was concurrent with visceral hypersensitivity. Increased spinal Fos expression suggests induction of central sensitization. These data demonstrate the development and maintenance of visceral hypersensitivity in estradiol-replaced animals following distal somatic injury and stress that mimics some characteristics reported in patients with temporomandibular disorder and comorbid irritable bowel syndrome. This new animal model is a powerful experimental tool that can be employed to gain further mechanistic insight into overlapping pain conditions.

Perspective: The majority of patients with temporomandibular disorder report symptoms consistent with irritable bowel syndrome. Stress and female prevalence are common to both conditions. In a new experimental paradigm in ovariectomized rats with estradiol replacement, masseter inflammation followed by stress induces visceral hypersensitivity that persists for months, modeling these comorbid pain conditions.

Keywords: Comorbid pain; estrogen; irritable bowel syndrome; stress; temporomandibular disorder; visceral hypersensitivity.