Pain Type and Interstitial Cystitis/Bladder Pain Syndrome Treatment

GRA provides a global index used to rate the response of a condition to an intervention. The GRA is a 7-point centered scale that assesses patient impression of change in IC/BPS symptoms since entering the study ranging from 7= "very much worse" to 1= "very much improved." This scale will be administered at post-treatment and at follow-up. Global improvement is a core domain recommended for conducting clinical trials of the efficacy and effectiveness of treatments for chronic pain according to Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT). We will examine the mean differences in GRA scores by phenotype in each treatment condition, and we will then calculate the percentage of patients classified as treatment responders (GRA<3) within each treatment and phenotype.

The COPCS is designed to identify up to 10 chronic overlapping pain conditions that often occur together in the same individual. The first part of the survey presents a body map, inquiring about pain locations. Based on participant responses to the body map, additional questions about symptoms are asked to determine the type of pain conditions that are experienced. Endorsed pain locations are collapsed into "regions" to reflect the number of zones in the body with pain (1-7 pain regions). Participants will be categorized into "peripheral" or "centralized" pain types based on the number of pain regions endorsed. This information will be used to examine the role of pain type in treatment response, and to assess how treatment outcomes may differ within pain phenotypes.

Psychophysical testing methods replicated existing protocols used at VUMC and include the following elements: 1) an evaluation of temporal summation (as a biomarker for central sensitization), 2) thermal pain threshold and tolerance. Thermal measures involved four pain threshold trials, followed by four pain tolerance trials, with the probe applied to slightly different target sites for each trial to avoid local sensitization. Means for the four threshold and tolerance trials are separately derived, and tolerance is reported here. Scores range from 0 = "No Pain or Warmth" to 10 = "Worst Possible Pain", with higher scores indicating a higher pain tolerance. This information will inform both how pain tolerance may predict treatment response, and change in response to treatment.

Psychophysical testing methods replicated existing protocols used at VUMC and include the following elements: 1) an evaluation of temporal summation (as a biomarker for central sensitization), 2) thermal pain threshold and tolerance. Thermal measures involved four pain threshold trials, followed by four pain tolerance trials, with the probe applied to slightly different target sites for each trial to avoid local sensitization. Means for the four threshold and tolerance trials are separately derived, and threshold is reported here. Scores range from 0 = "No Pain or Warmth" to 10 = "Worst Possible Pain", with higher scores indicating a higher pain threshold. This information will inform both how pain threshold may predict treatment response, and change in response to treatment.

Psychophysical testing methods will replicate existing protocols used at VUMC and include an evaluation of temporal summation (as a biomarker for central sensitization). Temporal summation includes a series of 10 sequential heat pulses applied to the forearm. In each sequence, after each heat pulse, subjects provide a verbal numeric pain intensity rating on a 0-10 scale (0 = "No Pain or Warmth" and 10 = "Worst Possible Pain"). The standardized slope of the line fitted to the series of 10 pulses at each temperature indexes temporal summation and serves as a quantitative marker of central sensitization. Two slopes will be calculated from two sequences. These slopes reflect the relationship between pain and pulse, representing average pain increase for each unit increase in pulse. This information will inform both how temporal summation may predict treatment response, and change in response to treatment.

Urinalysis will be used to assess for infection and urinary biomarkers associated with pain phenotype. Urinary Nerve Growth Factor will be collected to assess the potential impact of inflammation detected in the urine on treatment response, and whether any change in this biomarker may occur following treatment.

Urinalysis will be used to assess for infection and urinary biomarkers associated with pain phenotype. Urinary Interleukin-6 will be collected to examine the potential impact of pro-inflammatory cytokines detected in the urine on treatment response, and whether any change in this biomarker may occur following treatment.

Blood samples will be taken and stimulated with lipopolysaccharide (LPS) to assess for the presence of low-grade inflammation in the blood. Changes in blood samples will be taken to assess for inflammatory biomarkers, including LPS-stimulated cytokines to facilitate patient phenotyping and assess whether IL6-LPS may predict treatment response and change in response to treatment.