Hypothesis / aims of study
As an induced state of spinal hypersensitivity and a well-recognized mechanism of centrally amplified pain perception that facilitates afferent signaling, it is plausible that central sensitization (CS) may contribute to manifestations of Overactive Bladder (OAB) symptoms in some women. Individuals with CS characteristically report greater psychosocial and somatic symptom burden. The aim of the study was to determine if subgroups of women with OAB identified by cluster analyses based on psychosocial characteristics would demonstrate varying degrees of heat pain temporal summation.
Study design, materials and methods
After Internal Review Board approval, we enrolled 97 women with idiopathic OAB from the Urology clinic and through advertisement, using a score of >= 4 on the OABq-V3 to confirm the diagnosis. Participants completed questionnaires detailing demographic and clinical history as well as OAB symptoms (OAB questionnaire) and urinary tract symptoms (ICIQ-Female LUTS questionnaire). To assess psychosocial symptom burden, the subjects completed the PROMIS depression, anxiety, and pain short form items and the perceived stress scale. As a measure of somatic symptom burden, they completed the Central Sensitivity Index (CSI) Subjects then underwent quantitative sensory testing to measure thermal cutaneous temporal summation (TS) on the ventral forearm, with a series of 10 oscillating heat pulses to 49°C of 0.4 hertz. Immediately after the peak of every heat pulse, subjects provided a verbal numeric pain intensity rating using a 0 – 100 visual analog scale (VAS). We calculated a standardized slope fitted to the first 5 pain ratings for each subject to serve as the primary index of TS. We performed a two-step cluster analysis incorporating the PROMIS depression, anxiety, and pain scores, perceived stress scale, and the CSI, with the derived clusters representing the primary exposure measures for the data analyses. Statistical analyses using T-test and linear regression compared clinical variables across the primary exposures of cluster groups. For regression analysis of TS, we also included the initial VAS pain score at the first heat trial as an effect modifier to control for confounding due to baseline effects on observed slopes (i.e., floor or ceiling effects).
Cluster analyses identified two cluster groupings with 29 subjects in Cluster 1 and 68 in Cluster 2 , demonstrating moderate separation (silhouette index = 0.5). Characteristics of the cluster variables are demonstrated in Table 1, with the relative importance of each individual factor on the clustering represented by descending order. Cluster 1 represented an overall increased burden of psychosocial symptoms compared to Cluster 2. Age and BMI did not differ between the two groups (Table 2). However, OAB symptom burden and health-related quality of life score were significantly higher for Cluster 1 compared to Cluster 2. In addition, total urinary symptom severity, as well as sub-scores for filling, and voiding symptoms, were higher in Cluster 1. There was no difference in incontinence severity. During the TS protocol, the means of the initial VAS rating were similar between the two groups (38.8 vs. 35.5, p=.5). The mean slope of the TS was significantly higher for Cluster 1 compared to Cluster 2, including adjustment for initial VAS pain score (Beta = 1.8, SE = .83 t = 2.15, p =.03).
Interpretation of results
In this sample of women with OAB, a subgroup defined by increased burden of psychosocial and somatic characteristics not only demonstrated increased OAB-specific and lower urinary tract symptom severity, but also demonstrated higher levels of TS during quantitative sensory testing. This difference in TS indexes suggests that some women with OAB appear to have CS, which is also reflected by increased psychosocial symptom burden. The implications for management of these women with CS remains to be determined; however, this study which maps clinical phenotypes to postulated disease mechanisms represents a first step towards mechanistic-directed OAB management.