Local blockade of integrins in the temporomandibular joint region reduces Fos-positive neurons in trigeminal subnucleus caudalis of female rats produced by jaw movement

This study assessed the influence of integrins on trigeminal brainstem neural activity evoked during jaw movement (JM). Limited range of motion and pain during jaw opening are common complaints of patients with temporomandibular joint (TMJ) disorders. JM (0.5 Hz, 30 min) was presented to ovariectomized (OvX) female rats given estrogen replacement and males under barbiturate anesthesia. Quantification of Fos-like immunoreactivity (Fos-LI) after JM served as an index of evoked neural activity. Rats were injected locally in the TMJ with either an active (GRGDS, 300 μM, 25 μl) or an inactive integrin antagonist (SDGRG) prior to JM. The effect of prior inflammation of the TMJ region was assessed in separate groups of rats by injecting bradykinin (10 μM, 25 μl) with or without integrin drugs prior to JM. Active integrin antagonist significantly reduced JM-evoked Fos-LI in superficial laminae at the trigeminal subnucleus caudalis/upper cervical cord (Vc/C₂) junction in OvX compared to male rats independent of bradykinin pretreatment. Fos-LI produced in the dorsal paratrigeminal and trigeminal subnucleus interpolaris/caudalis (Vi/Vc) transition regions was not reduced by active integrin antagonist in males or OvX females. Active integrin antagonist did not affect Fos-LI produced after injection of bradykinin alone into the TMJ. These results suggest that RGD binding integrins contribute to JM-evoked neural activity at the Vc/C₂ junction under naive and inflamed conditions in a sex-dependent manner.