Stress is one of the most comnrion experiences, and stress modulates many other experiences including pain. Stress that is perceived as uncontrollable, chronic or unpredictable may, over time, induce long-term pathophysiological changes. Instead'of being inhibited, responses to painful stimuli become augmented, a phenomenon known as stress-induced hyperalgesia (SIH). While SIH is associated with multiple painful diseases, including disorders of the urinary bladder, at present it has no mechanistic explanation. The proposed studies will test one potential mechanism related to stress-induced neuropeptide release. Using the urological pain model that is central to the current research in the laboratory, we will test the hypothesis that chronic stress induces release of spinal urocortins which activate spinal corticotropin-releasing factor-2 (CRF2) receptors to modulate spinal nociceptive transmission from the urinary bladder. The specific subhypotheses that refine and develop the general hypothesis will be tested in the following specific aims:
Specific Aim 1 will determine the distribution of urocortin (Ucn) II immunoreactivity in the spinal cord following exposure to chronic footshoclt.
Specific Aim 2 will determine the source of Ucn II to the spinal cord.
Specific Aim 3 will determine whether chronic stress alters expression of CRF receptors in the spinal cord.
Specific Aim 4 will determine whether chronic stress, urocortins and CRF receptor activation alter urinary bladder sensory processing.
The aims of this proposal will utilize molecular biology, immunohistochemistry, electrophysiology and behavioral techniques to gain a better understanding of SIH in a urological system by dissecting out the role of one of the many possible modulators of pain sensation.
|Hall, Jason D; DeWitte, Cary; Ness, Timothy J et al. (2015) Serotonin enhances urinary bladder nociceptive processing via a 5-HT3 receptor mechanism. Neurosci Lett 604:97-102|
|Robbins, Meredith T; Deberry, Jennifer; Randich, Alan et al. (2011) Footshock stress differentially affects responses of two subpopulations of spinal dorsal horn neurons to urinary bladder distension in rats. Brain Res 1386:118-26|
|DeBerry, Jennifer; Randich, Alan; Shaffer, Amber D et al. (2010) Neonatal bladder inflammation produces functional changes and alters neuropeptide content in bladders of adult female rats. J Pain 11:247-55|
|Robbins, Meredith T; Mebane, Hannah; Ball, Chelsea L et al. (2010) Effect of estrogen on bladder nociception in rats. J Urol 183:1201-5|