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| FUNCTIONAL MAGNETIC RESONANCE IMAGING DURING CONTROLLED NOXIOUS STIMULATION IN MEN AND WOMEN David Borsook1,3, M.D., Ph.D., Lino Becerra2, Ph.D., Hans Breiter2, 5, M.D., Alison Comite1, B.S., R. Gilberto Gonzalez2,4 , M.D. Ph.D. MGH Pain Center1 and MGH NMR Center2 Gender is a significant factor in understanding the biology of a particular function. Human gender differences are present in both experimental pain responses and prevalence of painful diseases. In general, women exhibit an increased sensitivity to acute pain compared with men. The reasons for the differences observed in human experiments are unclear, and a number of possibilities have been proposed. These include experimenter gender, subject size, and phase of the menstrual cycle and "menstrual age". Specific biological mechanisms that may underlie gender differences include: (1) sensitization of afferent pain fibers/nociceptors by ovarian hormones; (2) changes in descending/modulatory pain systems at different times of the menstrual cycle, including sex differences in the stress (also different CNS regions involved in stress induced analgesia contain steroid receptors which may alter the response) (3) decreased or absent responses to analgesics, such as morphine at different times of the menstrual cycle (differing responses to opioid agonists have been shown to exist between men and women, with greater postoperative analgesia in women); and (4) gender differences in autonomic responses to pain. Numerous methods have been used to characterize changes related to gender differences, but have been hampered by the lack of objective methodologies. Recently, however, technological advances have allowed us to visualize changes in neural activity in both patients and normal volunteers. Functional magnetic resonance imaging (fMRI), a relatively new technique, provides a safe means for measuring changes in the human brain following sensory stimuli or drug administration without any radiation exposure, and can acquire data throughout the entire brain continuously up to one hour with a temporal resolution as low as 2 seconds. Of particular value in the study of pain, fMRI permits the acquisition over time of changes associated with the response of the nervous system, with enhanced spatial resolution. Thus, we are now able, for example, to observe changes associated with the development of hyperalgesia (an experimental form of acute injury where rapid plasticity or sensitization in the nervous system results in altered sensory processing). In our studies, we exploit fMRI techniques to map brain regions activated by noxious and non-noxious heat so as to define CNS circuitry in men and women and correlate objective measurements (fMRI) with psychophysical measurements. We present preliminary data on relative activation in cohorts of men and women and changes observed in women at 2 phases of their menstrual cycle (mid-follicular and mid-luteal phase) following controlled thermal stimulation. These studies should substantially improve our knowledge of underlying neurobiological mechanisms, gender differences in pain processing in acute and chronic conditions, and differing effects of pharmacological agents in men and women. Supported in part by the Ruth Freeman Fund for Pain Research and the Melvin J. Fisher Fund for Pain Research, Massachusetts General Hospital, Harvard Medical School.
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