Sex Differences in Brainstem Neural Activation after Injury to the TMJ Region

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Abstract
The basis for a higher prevalence of painful temporomandibular disorders (TMD) among women than men is not known. The present study used Fos-like immunoreactivity (Fos-LI) to quantify the pattern and magnitude of neural activation within the trigeminal brainstem complex of male and female rats caused by acute inflammatory injury to the temporomandibular joint (TMJ) region. Also, Fos-LI was assessed in animals given morphine, a preferential mu opioid receptor agonist, or U50,488H, a selective kappa opioid agonist, prior to TMJ injury to determine if opioid modulation of neural activation was similar in males and females. The general pattern of Fos-LI after TMJ injury was similar in males and females. This pattern was characterized by a high density of Fos-positive neurons in the dorsal paratrigeminal nucleus (dPa5), subnucleus interpolaris/caudalis transition region (Vi/Vc-vl), and in the superficial laminae at the subnucleus caudalis/upper cervical spinal cord (Vc/C2) junction ipsilateral to TMJ injury. In contrast to other regions the number of Fos-positive neurons produced at the Vc/C2 junction was proportional to the concentration of mustard oil injected into the TMJ region. In addition, proestrus females produced higher levels of Fos-LI at the Vc/C2 junction than diestrus females or males. Morphine caused a greater dose-related reduction in Fos-LI at the dPa5 and Vc/C2 junction in males than females. By contrast, U50,488H caused a dose-related reduction in Fos-LI only at the Vc/C2 junction of proestrus females. These results support the hypothesis that the Vc/C2 junction region plays a critical role in the integration of pain signals originating from the TMJ region and may underlie sex differences in sensory processing related to TMJ pain.