The present set of studies seeks to determine whether serotonergic systems exert differential effects on nociceptive processing in models of deep tissue hypersensitivity. A single Specific Aim is thus proposed: To characterize the effect of stress and a systemically administered SSRI and SNRI on both bladder and somatic sensory processing in female rats with and without pristane-induced arthritis. The initial experiments will expand upon preliminary studies and will assess the effect of systemic administration of an SSRI, paroxetine, and an SNRI, milnacipram, on stress-induced bladder hypersensitivity, measured by urinary bladder distension-evoked (UBD) visceromotor reflex responses (VMRs), following chronic exposure to a psychological stressor, water avoidance. Somatic nociception and locomotion will also be measured in these animals. A second set of experiments will examine whether exposure to chronic psychological stress alters mechanical paw withdrawal threshold and locomotion in rats with pristane-induced arthritis and will ascertain the effect of both reuptake inhibitors on stress-induced changes. Nociceptive responses to bladder distension will also be measured in these animals to determine whether comorbidity with a somatic disorder alters effects of serotonin reuptake in visceral systems. The proposed studies will not only provide insight into the role of stress as a potential exacerbator of multiple types f deep tissue pain, but will also yield a better understanding of serotonergic systems related to pain modulation. By utilizing two separate animal models these studies will be some of the first to define the relationship between stress and symptom exacerbation in pains with both visceral and somatic origins. By using two different classes of drugs, these studies will give a clinically relevant comparison of currently available drug options.

Public Health Relevance

The proposed studies examining the role of serotonergic systems in stress-induced bladder hypersensitivity will give insight related to the interaction of two key modulators of nociceptive processing. Furthermore, these studies will determine whether another chronic deep tissue pain, rheumatoid arthritis, is similarly affected by stress and serotonergic modulation. An improved understanding of sensory processing as it relates to these chronic, co-morbid pain syndromes and of the complexity of serotonergic systems as they relate to descending pain modulation could lead to the development of therapeutic options for the treatment of chronic pain.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Special Emphasis Panel (ZDK1-GRB-8 (O2))
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Kirkali, Ziya
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University of Alabama Birmingham
Schools of Medicine
United States
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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
Goodin, Burel R; Ness, Timothy J; Robbins, Meredith T (2015) Oxytocin - a multifunctional analgesic for chronic deep tissue pain. Curr Pharm Des 21:906-13
Goodin, Burel R; Anderson, Austen J B; Freeman, Emily L et al. (2014) Intranasal Oxytocin Administration is Associated with Enhanced Endogenous Pain Inhibition and Reduced Negative Mood States. Clin J Pain :