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

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.

Estrogenic influences in pain processing

“…This is further supported by studies showing enhanced sensitization of neurons in the trigeminal subnucleus caudalis during late proestrus and estrus when estrogen levels decline abruptly (Martin et al, 2007), and a significant dose-dependent influence of estradiol (daily subcutaneous injections of 2 g or 20 g estradiol for three days) on the encoding properties of the nociceptivespecific neurons in lamina I-II in the medullary dorsal horn of ovariectomized female rats (Tashiro et al, 2007). The neurons in laminae I-II at the subnucleus caudalis/C2-junction have been shown to play a critical role in mediating sex differences related to temporomandibular pain (Bereiter, 2001;Bereiter and Okamoto, 2011). Large amounts of ER-expressing neurons are present in these laminae of the trigeminal subnucleus caudalis (Amandusson et al, 1995;Vanderhorst et al, 2005) (Fig.…”

Convergence of nociceptive information from temporomandibular joint and tooth pulp afferents on C1 spinal neurons in the rat

“…But the characterization of the afferent inputs from the TMJ has not yet been determined. Acute injury to the TMJ region results in a high density of Fos-positive neurons in the areas including the trigeminal spinal subnucleus caudalis (Vc) and upper cervical cord junction region (Vc/C2) (Hathaway et al, 1995;Bereiter and Bereiter, 2000;Bereiter, 2001). Based on evidence that the Vc/C2 region was excited by mechanical and/or chemical stimulation of the TMJ region, Takeshita et al (2001) concluded that neurons in the lamina I-II in the Vc/C2 region play an important role in mediating pain sensation in TMD.…”

The Protective Role of Testosterone in the Development of Temporomandibular Joint Pain

“…9 Similar results were also obtained by the TMJ injection of other algogenic agents. 4,6,25 The cause of this lower sensitivity to experimentally induced TMJ nociception in male rats than in female rats as well as the lower prevalence of many pain conditions, 29 including TMJ pain 21 in men than in women, has not as yet been clarified. Although it might be attributed to a pronociceptive effect of ovarian hormones, 6,10,21 an antinociceptive effect of ovarian hormones has also been reported in animal 9 and human 22 studies.…”