Clinical Science | Basic Science: CNS Mechanisms | Basic Science: PNS Mechanisms

Ionic Mechanisms of TMJ Pain

Principal Investigator: Michael S. Gold, Ph.D.

Temporomandibular disorders (TMD) are often associated with debilitating pain. While both men and women may suffer from TMD pain, the vast majority of those seeking medical attention for relief from TMD pain are women, whose pain is likely to be more severe and last longer than that experienced by men. Indeed, over 80% of those seeking medical attention for relief of TMD pain are women. The molecular basis for the gender difference in the expression and prevalence of TMD pain remains unknown. However, epidemiological, clinical and experimental evidence suggests that gonadal hormones, in particular estrogen, contribute to this difference. Furthermore, there are several lines of evidence to suggest that a target for estrogen contributing to gender differences in TMD pain is the primary sensory neuron innervating the temporomandibular joint (TMJ). Importantly, estrogen may influence the excitability of TMJ afferents in normal tissue as well as the increase in excitability observed in the presence of inflammation.

In normal tissue, voltage- and Ca²⁺-activated channels present in the plasma membrane of the afferent terminal control afferent excitability. Changes in the biophysical properties, expression and/or distribution of these channels may have a profound impact on afferent excitability, however, little is known about the impact of estrogen on ion channels in sensory neurons. Furthermore, while several mechanisms mediating acute actions of inflammatory mediators on sensory neurons have been identified, considerably less is known about mechanisms mediating hyperexcitability in the presence of persistent inflammation and virtually nothing is known about the impact of estrogen on these processes. This is particularly true for joint afferents given the dearth of data on the basic membrane properties of these afferents innervating normal tissue. Therefore, this project tests the following hypotheses: 1) that estrogen increases the sensitivity of the TMJ to noxious stimulation and exacerbates inflammation-induced increases in sensitivity; 2) that estrogen influences the excitability of TMJ neurons through a direct action on these neurons; 3) that estrogen-induced changes in the excitability of TMJ afferents reflects a changes in the expression of voltage- and/or Ca²⁺ activated channels in these neurons; and 4) that estrogen exacerbates inflammation-induced increases in the excitability of TMJ afferents by influencing inflammation-induced changes in the voltage and/or Ca²⁺ activated channels in these neurons. These hypotheses are being tested in a series of experiments employing a combination of behavioral, anatomical, electrophysiological and molecular biological techniques in laboratory animals.

References

Flake , N.M., Hermanstyne, T.O. and Gold, M.S. (2006) Testosterone and estrogen have opposing actions on inflammation-induced plasma extavasation in the rat temporomandibular joint. Am J Physiol, 291(2):R343-8.

Flake, N.M., Bonebreak, D.B., and Gold, M.S. (2005) Estrogen and inflammation increase the excitability of rat temporomandibular joint afferent neurons. J. Neurophysiol 95(3): 1585-1597.

Flake, N.M., and Gold, M.S., (2005) Inflammation alters sodium currents and excitability of temporomandibular joint afferents. Neurosci. Lett. Aug 26; 384(3): 294-299.

Michael S. Gold, Lei Zhang, Dena L. Wrigley, and Richard J. Traub. Prostaglandin E2 Modulates TTX-R INa in Rat Colonic Sensory Neurons. J Neurophysiol. 88: 1512-1522, 2002.

Thut P.D., Hermanstyne T.O., Flake N.M., Gold M.S.   An operant conditioning model to assess changes in feeding behavior associated with temporomandibular joint inflammation in the rat. J Orofac Pain, 21(1):7-18, 2007.