Challenges in drug discovery for overcoming 'dysfunctional pain': an emerging category of chronic pain - Beyond the Abstract

Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic condition characterized by recurring pain in the bladder and nearby pelvic region. The pain in IC/PBS could fall into “dysfunctional pain” in that definitive organic disorder such as inflammation, infection or neuropathy, which explains the persistent pain, has not been identified. Namely, the underlying pathophysiology for the pain in IC/PBS, like other dysfunctional pain-associated diseases such as fibromyalgia, has not been identified.

Despite a great number of patients are suffering the pain in IC/PBS (1), there has been no consistently effective treatment. Thus, the development of better therapies is a topic of critical interest. Given the unknown pathophysiology is standing in the way of establishment of new therapies, a pivotal focus of future research will be on exploration and identification of it.

One of recent topics regarding the pathophysiology for the pain in IC/PBS is the possible involvement of nerve growth factor (NGF). It has been reported that tanezumab, a monoclonal antibody of NGF, significantly reduces pain scores in patients with IC/PBS, especially in women (2). A recent study using a putative animal model of the pain in IC/PBS has also supported the involvement of NGF in the pathophysiology (3). The modulation of NGF signal might be a promising approach to reduce the pain in IC/PBS, although further studies are warranted to verify the efficacy and the safety.

It is of interest that an altered endogenous pain control system occurs in patients with IC/PBS in common with other dysfunctional pain-associated diseases such as fibromyalgia and irritable bowel syndrome (4). This may suggest a possible existence of common underlying pathophysiology between IC/PBS and other dysfunctional pain-associated diseases.

Future research on exploration and identification of the underlying pathophysiology for the pain in IC/PBS is warranted. Such research would lead to the development of new effective therapies for the pain in IC/PBS as well as that in other dysfunctional pain-associated diseases.

References:
1. Berry SH, Elliott MN, Suttorp M, Bogart LM, Stoto MA, Eggers P, Nyberg L, Clemens JQ. Prevalence of symptoms of bladder pain syndrome/interstitial cystitis among adult females in the United States. J Urol 2011;186:540-4.
2. Nickel JC, Krieger J, Mills I, Crook T, Jorga A, Atkinson G, Smith M. Tanezumab reduces pain in women with interstitial cystitis/bladder pain syndrome. J Urol 2015;193 (suppl): e397.
3. Fujita M, Kasai E, Omachi S, Sakaguchi G, Shinohara S. A novel method for assessing bladder-related pain reveals the involvement of nerve growth factor in pain associated with cyclophosphamide-induced chronic cystitis in mice. Eur J Pain 2015 (in press).
4. Ness TJ, Lloyd LK, Fillingim RB. An endogenous pain control system is altered in subjects with interstitial cystitis. J Urol 2014;191:364-70.

Written by:
Yukinori Nagakura
Aomori University, Faculty of Pharmaceutical Sciences,
2-3-1 Kohbata, Aomori-shi, Aomori 030-0943, Japan
Tel: +81 17 738 2001; Fax: +81 17 738 2411
E-mail: .

Abstract: Challenges in drug discovery for overcoming 'dysfunctional pain': an emerging category of chronic pain

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