ROLE OF ESTROGEN AND PROGESTERONE IN SCI PAIN

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Chronic central pain develops in the majority of spinal cord injury (SCI) patients following complete and partial injuries, including at level allodynia (pain to touch in dermatomes at and just above the level of injury). Using a recently developed electrophysiological rat model (in vivo) for investigating the effects of chronic SCI on responses in supraspinal neurons, new data from our lab was obtained which indicates that the development of at level allodynia is dramatically reduced after SCI in female rats with normal hormonal cycles compared to males/ovariectomized females. This raises the possibility that progesterone and/or estrogen could play therapeutic roles for SCI-induced pain. We also have evidence supporting the hypothesis that at level allodynia, if and when it develops, may result from damage to descending pathways in the dorsolateral quadrant in combination with sparing of at least a portion of ascending tract(s) in the ventrolateral quadrant that transmit, to higher centers, the information from dermatomes just above the level of injury. Moreover, preliminary data indicate that the allodynia, when it develops, may be exacerbated by circulating progesterone and/or estrogen, which is clearly seen in the responsiveness of brainstem neurons. This exacerbation is consistent with findings for numerous conditions with cycle related changes in pain thresholds in humans. Thus, the development and perpetuation of at level allodynia will be examined relative to experimental variations of hormonal status and variations in specific patterns of damage/sparing. The underlying mechanism may include changes in the responses of neurons in the thalamus (an important region involved in the processing of inputs that ultimately lead to pain), which will be compared to the concomitant behavioral signs that accompany these changes (i.e., allodynia). Thus, a unique feature of this proposal is the multidisciplinary approach that is taken, i.e., using electrophysiological, behavioral and anatomical measures for each animal. The proposed research will examine the underlying mechanisms related to ovarian hormones that prevent the development and contribute to the perpetuation of this clinically-relevant at level allodynia. Therefore, these studies will lead to a better understanding of the neural mechanisms underlying SCI pain and will identify ovarian hormones as targets that can readily be modulated to prevent and treat SCI-related pain. This is very important, since current drug therapies and surgical interventions are inadequate.