Induction of orofacial pain potentiates fibromyalgia symptoms in mice: Relevance of nociceptin system.

Aims: Fibromyalgia patients might experience temporomandibular disorder (TMD) as a comorbidity. However, the connection between these two syndromes is not fully understood. Nociceptin (N/OFQ) and NOP receptors are implicated in both conditions, but their relevance in the comorbidity needs investigation. This study featured a comorbidity model of fibromyalgia plus TMD in mice, attempting to evaluate the significance of the N/OFQ-NOP receptor in this paradigm.

Materials And Methods: Female CF-1 mice were submitted to the fibromyalgia model induced by three daily consecutive injections of reserpine (0.25 mg/kg) and received an intra-masseter injection of complete Freund's adjuvant (CFA; 10 μl; diluted 1:1) on day four.

Key Findings: There was a rise in nocifensive and depression-like behaviors in the comorbidity group, as evaluated by the Grimace scores and the tail suspension test (TST). This group displayed anxiogenic-like effects in the hole board and the elevated plus maze tests. The comorbidity group showed an increment of c-Fos immunopositivity in the ipsilateral side of CFA injection, in the trigeminal ganglion (TG) and thalamus. The administration of N/OFQ (1 nmol/kg, i.p.) boosted the Grimace scores in the comorbidity group, with no effect for the NOP receptor antagonist UFP-101 (1 nmol/kg, i.p.). Either NOP ligand failed to alter depression or anxiety behavioral changes. Alternatively, pregabalin (30 mg/kg; i.p.) reduced the nociceptive responses and the number of head dips in the hole board.

Significance: Data reveal new evidence suggesting that inducing TMD with CFA may worsen fibromyalgia symptoms in reserpine-treated mice, an effect partially regulated by systemic N/OFQ.