Acute injury to the temporomandibular joint (TMJ) region activates neurons in multiple, but spatially discrete, areas of the trigeminal spinal nucleus as seen by an increase in Fos-like immunoreactive neurons (Fos-LI). Pretreatment with morphine greatly reduces Fos-LI produced in the dorsal paratrigeminal area (dPa5), ventrolateral pole of the subnucleus interpolaris/caudalis (Vi/Vc-vl) transition region, and laminae I-II at the subnucleus caudalis/upper cervical cord junction (Vc/C2) suggesting a role for these areas in processing pain signals from the TMJ region. To determine if vagal afferents contribute to neural activation after TMJ injury or reduction of activity after morphine, Fos-LI was quantified in the lower brainstem and upper cervical spinal cord of intact and vagotomized male and female rats under barbiturate anesthesia. Bilateral cervical vagotomy (VgX) did not affect Fos-LI produced by TMJ injury in males or females in the absence of morphine. By contrast, morphine-induced reduction in Fos-LI produced at the Vi/Vc-vl transition region was prevented by prior VgX in males and diestrus females, but not in proestrus females. Morphine inhibition of Fos-LI produced in laminae I-II at the Vc/C2 junction region was diminished in vagotomized males compared to intact animals, but not affected in females. In an autonomic control area, the caudal ventrolateral medulla (CVLM), VgX reversed the morphine-induced reduction in Fos-LI in males and females similarly compared to their respective intact controls. These results were consistent with the hypothesis that the Vi/Vc-vl transition region plays a unique role in deep craniofacial pain processing and may integrate autonomic and opioid-related modulatory signals in a manner dependent on sex hormone status.
Bibliographical noteFunding Information:
The authors thank Dr Harumitsu Hirata for helpful comments in preparing the manuscript. This study was supported in part by a grant from the NIDCR (DE-12758).
- C-fos gene
- Opioid analgesia
- Sex differences
- Temporomandibular joint
- Trigeminal spinal nucleus
- Vagus nerve