An endogenous pain control system is altered in subjects with interstitial cystitis

Abstract

Purpose: Multiple studies have demonstrated that in healthy subjects, painful stimuli applied to one part of the body inhibit pain sensation in other parts of the body, a phenomenon referred to as conditioned pain modulation. Conditioned pain modulation is related to the presence of endogenous pain control systems. Studies have demonstrated deficits in conditioned pain modulation associated inhibition in many but not all chronic pain disorders. In this study we determine whether conditioned pain modulation is altered in subjects with interstitial cystitis/bladder pain syndrome.

Materials and methods: Female subjects with and without the diagnosis of interstitial cystitis/bladder pain syndrome were studied psychophysically using quantitative cutaneous thermal, forearm ischemia and ice water immersion tests. Conditioned pain modulation was assessed by quantifying the effects of immersion of the hand in ice water (conditioning stimulus) on threshold and tolerance of cutaneous heat pain (test stimulus) applied to the contralateral lower extremity.

Results: The conditioned pain modulation responses of the subjects with interstitial cystitis/bladder pain syndrome were statistically different from those of healthy control subjects for cutaneous thermal threshold and tolerance measures. Healthy control subjects demonstrated statistically significant increases in thermal pain tolerance whereas subjects with the diagnosis of interstitial cystitis/bladder pain syndrome demonstrated statistically significant reductions in thermal pain tolerance.

Conclusions: An endogenous pain inhibitory system normally observed with conditioned pain modulation was altered in subjects with interstitial cystitis/bladder pain syndrome. This finding identifies interstitial cystitis/bladder pain syndrome as similar to several other chronic pain disorders such as fibromyalgia and irritable bowel syndrome, and suggests that a deficit in endogenous pain inhibitory systems may contribute to such chronic pain disorders.

Keywords: BPS; CPM; HC; IC; bladder pain syndrome; conditioned pain modulation; diffuse noxious inhibitory control; healthy control; interstitial cystitis; pain; urinary bladder.

Figure 1

Schematic diagram summarizing the testing protocol. Different segments were performed in the following sequential order with some randomization of order within segments indicated. Segments included the following measures: [1] Void Report, [2a] Heat Threshold, [2b] Heat Tolerance, [2c] Heat Intensity, [3] Ischemic Tolerance, [4] Ice Water Tolerance, [5a] CPM of Heat Threshold, [5b] CPM of Heat Tolerance and [5c] CPM of Heat Intensity. See text for more complete description. Pauses of 2–5 minutes between stimuli presentation allowed recovery of sensations to baseline.

Figure 2

Subjects with the diagnosis of Interstitial Cystitis reported significantly more pain with immersion of their hand in ice water (A) and during the ischemic forearm task (B) when compared with Healthy Controls. See text for specifics of testing. * and ** indicated significant difference from healthy controls with P<0.05 and P<0.01 respectively. Values are mean ± SEM.

Figure 3

Differences in hot thermal pain measures due to CPM were calculated as the difference between values measured in the lower extremity while the hand was immersed in ice water minus values measured in the lower extremity while the hand was immersed in room temperature water. Hot thermal pain tolerances due to CPM were statistically different in both subject groups but with a differential effect of CPM (opposite directions) reflected as an increase in difference value in healthy control subjects and as a decrease in difference value in IC/BPS subjects (# indicates difference from measures during room temperature with p<0.05). Hot thermal pain threshold changes due to CPM failed to achieve statistical significance. Due to the different directions of effect of CPM on the two subject groups, a comparison of the CPM effects revealed a statistically significant different effect of subject group on both pain threshold and pain tolerance measures (** indicates difference between two subject groups, p<0.01). Values are mean ± SEM.