Differential ascending projections of temporomandibular joint-responsive brainstem neurons to periaqueductal gray and posterior thalamus of male and female rats

Abstract

Several craniofacial pain conditions including temporomandibular joint disorders (TMJD) are more prevalent in women than men. The basis for sex differences in deep craniofacial pain is not known. The present study compared the magnitude of ascending projections from TMJ-responsive neurons in trigeminal brainstem to the ventrolateral periaqueductal gray (vlPAG) or posterior nucleus of the thalamus (Po) in males and female rats. Fluorogold (FG) was injected into vlPAG or Po and TMJ-responsive neurons were identified by Fos-like immunoreactivity (Fos-LI) after mustard oil injection. TMJ-evoked Fos-LI was similar in males and females; however, significant differences in cell counts were seen for FG single-labeled and Fos/FG double-labeled neurons in trigeminal brainstem. After vlPAG injections, the number of FG-labeled neurons in trigeminal subnucleus interpolaris (Vi), ventral interpolaris/caudalis transition (vl-Vi/Vc) and dorsal paratrigeminal region (dPa5) was greater in females than males. The percentage of Fos/FG double-labeled neurons in vl-Vi/Vc and dPa5 after vlPAG injection also were greater in females than males. By contrast after Po injections, males displayed a greater number of FG-labeled neurons in superficial laminae of Vc and C1–2 and deeper laminae at C1–2 than females. The percentage of Fos/FG double-labeled neurons in superficial laminae of Vc after Po injection also was greater in males than females. These data revealed significant sex differences in ascending projections from TMJ-responsive neurons in trigeminal brainstem. Such differences may influence the ability of males and females to recruit autonomic reflexes and endogenous pain control circuits relevant for TMJ nociception.

Sex Differences in Estradiol Secretion by Trigeminal Brainstem Neurons

“…Tran et al (2017) also concluded that ARO/GABA cells in Vc were interneurons; however, they did not report sex differences. A similar number of Fos-positive neurons in Vc were produced in OvX and male rats after intra-TMJ injection of AIC consistent with previous studies in which Fos production was similar for male and diestrous females (Bereiter, 2001) and for males and OvX rats given low maintenance doses of E2 (Chang et al, 2012). There are several possible explanations for observing increased TMJ-evoked secretion of E2 in OvX females, but not in males.…”

Medullary Norepinephrine Projections Release Norepinephrine into the Contralateral Bed Nucleus of the Stria Terminalis

“…Fluorogold infusions into the ventrolateral portion of the PAG bilaterally labels neurons in the A2 region. 43 Thus, PAG activation may antidromically activate the A2 group to elicit vBNST release, or this release could arise from another unidentified mechanism. Second, selective chemical inactivation with DSP-4 and 6-OHDA strongly suggest that noradrenergic neurons of the LC are not responsible for release in the vBNST.…”

Contribution of central sensitization to stress-induced spreading hyperalgesia in rats with orofacial inflammation

“…The symptoms of FMS in patients with mTMD are more severe and more prone to mental stress [ 22 , 23 ]. Both of TMD and FMS have higher incidence in female [ 20 , 24 ]. Because of this point, we used female rats to establish pre-clinical model to mimic the comorbidity of TMD and FMS.…”