Principal Investigator:

Co-investigators:

Joel D. Greenspan, Ph.D.

Eleni Sarlani, D.D.S, Ph.D.

Edward G. Grace, D.D.S.

This project addresses issues relevant to the CNS mechanisms of pain perception in terms of 1) gender differences in healthy individuals, and 2) factors contributing to temporomandibular disorder (TMD) pain. Two CNS mechanisms that influence nociceptive processing and resulting pain—temporal summation (TS) of pain and endogenous pain inhibitory systems—are being evaluated in a series of human experiments.

(larger view)

TS is the increase in perceived pain intensity when noxious stimuli of a constant intensity are delivered at a sufficiently rapid frequency. TS is centrally mediated and reflects transient up-regulation of nociceptive neurons’ excitability in the spinal cord, and potentially higher CNS regions. TS of heat pain has been reported to be greater in females than in males, suggesting that females may have more hyperexcitable central nociceptive neurons. Similarly, TMD patients have been reported to show higher temporal summation of heat pain than healthy controls, indicating that up-regulated central processing of nociceptive input may constitute an underlying pathophysiological basis of TMD. One purpose of this project is to elaborate on these observations, with reference to mechanically evoked pain. A variety of stimulation parameters and multiple measures will be employed to gain a more complete picture of this phenomenon. Moreover, it will be determined if there is a significant correlation between temporal summation of pain and measures of clinical pain in TMD patients.

Diffuse noxious inhibitory control (DNIC) is a phenomenon in which persistent noxious stimulation evokes an endogenous analgesic system, resulting in a global attenuation of nociceptive signals. Accordingly, subsequent noxious stimulation elsewhere on the body produces less pain than it otherwise would. Several studies indicate that DNIC engages the endogenous opiate system. Given gender differences in the efficacy of exogenous opiates, this project examines whether DNIC functions differently in men than women. Additionally, endogenous analgesic systems may be attenuated in cases of prolonged pain, thus contributing to the difficulty in managing chronic pain. This project compares DNIC efficacy in TMD pain patients vs. a healthy control group, to determine whether there is a significant difference in the evocation of the endogenous analgesic system.

Identifying the roles of these two specific nociceptive processing mechanisms in TMD pain would provide focus for the development of appropriately targeted pain relief treatments. Identifying gender differences in these two nociceptive processing mechanisms could explain, in part, the female prevalence of TMD, and possibly other chronic pain conditions. In addition, establishing such gender differences would highlight the need to consider the person’s sex in addressing pain treatment in general.

References

Moulton, E.A., Keaser, M.L., Gullapalli, R.P., Maitra, R., and Greenspan, J.D. Sex Differences in the Cerebral BOLD Signal Response to Painful Heat Stimuli. Am. J. Physiol. Regul. Integr. Comp. Physiol., 291:R257-67, 2006.

Sarlani, E. and Greenspan, J.D. Why look in the brain for answers to temporomandibular disorder pain? Cells Tissues Organs, 180:69-75, 2005.

Sarlani, E., Grace, E.G., Reynolds, M.A., and Greenspan, J.D. Sex differences in temporal summation of pain and aftersensations following repetitive noxious mechanical stimulation. Pain, 109:115-123, 2004.

Sarlani, E., Grace, E.G., Reynolds, M.A., and Greenspan, J.D. Evidence for upregulated central nociceptive processing in patients with masticatory myofascial pain. J. Orofac. Pain, 18:41-55, 2004.

Sarlani, E., Farooq, N.S., and Greenspan, J.D., Gender and laterality differences in thermosensation throughout the perceptible range. Pain, 106:9-18, 2003

Sarlani, E. and Greenspan, J.D. Evidence for generalized hyperalgesia in temporomandibular disorders patients. Pain, 102:221-226, 2003.

Sarlani E., Schwartz A.H., Greenspan J.D., Grace E.G. Chronic paroxysmal hemicrania: A case report and review of the literature. J. Orofac. Pain, 17:74-78, 2003.

Sarlani, E., Schwartz A.H., Greenspan J.D., and Grace E.G., Facial pain as first manifestation of lung cancer-related cluster headache and a review of the literature. J. Orofac. Pain, 17:262-267, 2003.

Sarlani, E. and Greenspan, J.D. Gender differences in temporal summation of mechanically evoked pain. Pain, 97:163-169, 2002.