Bladder pain syndrome (BPS or interstitial cystitis, IC) patients typically exhibit marked tenderness of pelvic floor musculature and that treatments directed solely at those muscles often resulted in marked improvement of bladder symptoms. This debilitating syndrome of unknown etiology is often postulated, but not proven, to be associated with microbial infection. To better understand the mechanisms that contribute to BPS/IC, we will study an animal model in which pelvic floor muscle injury alone (somatic injury) the degree to which damage- associated molecular patterns (DAMPs) signal through neuronal receptors that recognize pathogen-associated molecular patterns (PAMPs). A potential neurobiological mechanism for the behavioral changes observed with this injury model is the increased nociceptive signaling present in bladder-associated sensory ganglia. To this end, validation of our injury paradigm in the rodent as an experimental representation of BPS/IC provides us with a number of parameters with which to test potential mediators of somatic and visceral hypersensitivity. Furthermore, the outcomes of these proposed experiments may also provide potential therapeutic targets. Taken together, the use of a clinically-relevant animal model will provide us with the unique opportunity to improve PBS/IC diagnostic and treatment paradigms and increase the understanding of the mechanisms underlying the development and maintenance of chronic pelvic pain conditions in women.

Public Health Relevance

There is general agreement that bladder pain syndrome/interstitial cystitis (BPS/IC) is a visceral pain syndrome that also includes symptoms of urinary frequency, urgency and pain related to bladder filling. We will investigate the hypothesis that the nociceptive signaling which may account for the symptoms of pain may be due to the degree to which damage-associated molecular patterns (DAMPs) that signal through neuronal receptors that recognize pathogen-associated molecular patterns. This neuronal signaling may directly influence in the recurring discomfort or pain in the bladder and the surrounding pelvic region.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZDK1-GRB-8 (O2))
Program Officer
Kirkali, Ziya
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Indiana University-Purdue University at Indianapolis
Schools of Medicine
United States
Zip Code
Thinschmidt, Jeffrey S; Colon-Perez, Luis M; Febo, Marcelo et al. (2016) Depressed basal hypothalamic neuronal activity in type-1 diabetic mice is correlated with proinflammatory secretion of HMBG1. Neurosci Lett 615:21-7
Lahiri, Debomoy K; Maloney, Bryan; Bayon, Baindu L et al. (2016) Transgenerational latent early-life associated regulation unites environment and genetics across generations. Epigenomics 8:373-87
Wilson, Natalie M; Ripsch, Matthew S; White, Fletcher A (2016) Impact of Opioid and Nonopioid Drugs on Postsurgical Pain Management in the Rat. Pain Res Treat 2016:8364762
Xie, Jennifer Y; Chew, Lindsey A; Yang, Xiaofang et al. (2016) Sustained relief of ongoing experimental neuropathic pain by a CRMP2 peptide aptamer with low abuse potential. Pain 157:2124-40
Weber, Daniel J; Allette, Yohance M; Wilkes, David S et al. (2015) The HMGB1-RAGE Inflammatory Pathway: Implications for Brain Injury-Induced Pulmonary Dysfunction. Antioxid Redox Signal 23:1316-28
Park, Ki Duk; Yang, Xiao-Fang; Dustrude, Erik T et al. (2015) Chimeric agents derived from the functionalized amino acid, lacosamide, and the α-aminoamide, safinamide: evaluation of their inhibitory actions on voltage-gated sodium channels, and antiseizure and antinociception activities and comparison with lacosami ACS Chem Neurosci 6:316-30
Yoneda, Toshiyuki; Hiasa, Masahiro; Nagata, Yuki et al. (2015) Contribution of acidic extracellular microenvironment of cancer-colonized bone to bone pain. Biochim Biophys Acta 1848:2677-84
Yoneda, Toshiyuki; Hiasa, Masahiro; Nagata, Yuki et al. (2015) Acidic microenvironment and bone pain in cancer-colonized bone. Bonekey Rep 4:690
Due, Michael R; Yang, Xiao-Fang; Allette, Yohance M et al. (2014) Carbamazepine potentiates the effectiveness of morphine in a rodent model of neuropathic pain. PLoS One 9:e107399
Allette, Yohance M; Due, Michael R; Wilson, Sarah M et al. (2014) Identification of a functional interaction of HMGB1 with Receptor for Advanced Glycation End-products in a model of neuropathic pain. Brain Behav Immun 42:169-77

Showing the most recent 10 out of 11 publications