Bladder Distension Increases Blood Flow in Pain Related Brain Structures in Subjects with Interstitial Cystitis

Abstract

Purpose: In healthy control subjects certain brain regions of interest demonstrate increased regional cerebral blood flow in response to painful stimuli. We examined the effect of bladder distension on arterial spin label functional magnetic resonance imaging measures of regional cerebral blood flow in regions of interest in subjects with interstitial cystitis.

Materials and methods: A total of 11 female subjects with interstitial cystitis and 11 healthy controls underwent 3 brain perfusion scan studies using arterial spin label functional magnetic resonance imaging, including 1) with a full bladder, 2) with an empty bladder and 3) while experiencing heat pain. Regional cerebral blood flow was calculated using custom software and individual scans were spatially normalized to the MNI (Montreal Neurological Institute) template. Region of interest based, absolute regional cerebral blood flow was determined for each condition and for the within group/within subject regional cerebral blood flow distribution changes induced by each condition.

Results: Bladder distension was associated with robust increases in regional cerebral blood flow in subjects with interstitial cystitis. The increases were greater than those in healthy controls in multiple regions of interest, including the supplemental motor area (mainly Brodmann area 6), the motor and sensory cortex, the insula bilaterally, the hippocampal structures bilaterally, and the middle and posterior cingulate areas bilaterally. During heat pain healthy controls had more robust regional cerebral blood flow increases in the amygdala bilaterally. At baseline with an empty bladder there was lower regional cerebral blood flow in the insula, and the mid and posterior cingulate cortex bilaterally in subjects with interstitial cystitis.

Conclusions: Compared to healthy controls, subjects with interstitial cystitis have limited differences in regional cerebral blood flow in baseline (empty bladder) conditions as well as during heat pain. However, they had robust regional cerebral blood flow increases in the full bladder state in regions of interest typically associated with pain, emotion and/or motor control, indicating altered processing of bladder related sensations.

Keywords: brain; cerebrovascular circulation; cystitis, interstitial; pain; urinary bladder.

Figure 1

ROI by condition by groups analysis. Mean rCBF in each ROI for each condition for Healthy Control subjects (HCs; n=11) and Interstitial Cystitis subjects (ICs; n=11). Note how the rCBF in HCs does not vary as much across conditions as the ICs, especially during bladder pain. ANOVA was based on these data and showed significant main effects of condition (p=.012) and ROI (p.=000) and an ROI*Condition*Group interaction (p=.013).

Figure 2

FSL subtraction images showing rCBF differences between Interstitial Cystitis subjects (ICs) and Healthy control subjects (HCs) at rest (panel A); and changes in rCBF due to bladder filling (“full bladder” minus “empty bladder” states) in ICs (panel B) and in HCs (panel C). Color scale shows absolute rCBF difference (panel A) or change (panels B, C) in ml/100g/min. In panel A it is seen that the insular cortex has lower rCBF at rest in the ICs than in the HCs. (Cross hairs are centered on coordinates x = −40.7, y= −4.9, z= 1.3, where the mean rCBF was 12.7 ml/100g/min lower in the ICs). In panel B it is seen that ICs have rCBF increases or “activation” of the SMA bilaterally and of more posterior sections of the cingulate cortex. (Cross hairs in Fig 2b are centered on coordinates x= 11.3, y= −0.6, z= 62.6 where rCBF increased by 15.2 ml/100g/min). In addition some midbrain regions, including the periaquaductal gray matter, are also activated. In panel C it is seen that there is less extensive activation in HCs but definite involvement of the cerebellum and amygdala (which is also activated in ICs).

Figure 3. SPM results of bladder pain activation in IC subjects

SPM of whole brain data was conducted as a secondary assessment to determine whether unidentified ROIs were apparent and whether strongest findings using focused ROI analysis also appear on SPM’s more whole brain, “data driven” approach. Color scale shows values of t in SPM analysis of full bladder-induced rCBF changes including the SMA and posterior cingulate cortex. Significance level of the brightest spots is approximately p=.0002 and of the darkest spots is approximately p=.03. Cross hairs are centered on coordinates x= −6.0, y=0.0, z= 54, in the SMA. Thus, there was substantial overlap between our most significant ROI findings and the SPM activation map. Specifically, both analyses point to the SMA and several regions of the cingulate cortex as areas of activation.