Brain functional and anatomical changes in chronic prostatitis/chronic pelvic pain syndrome

Abstract

Purpose: Research into the pathophysiology of chronic prostatitis/chronic pelvic pain syndrome has primarily focused on markers of peripheral dysfunction. We present the first neuroimaging investigation to our knowledge to characterize brain function and anatomy in chronic prostatitis/chronic pelvic pain syndrome.

Materials and methods: We collected data from 19 male patients with chronic prostatitis/chronic pelvic pain syndrome, and 16 healthy age and gender matched controls. Functional magnetic resonance imaging data were obtained from 14 patients with chronic prostatitis/chronic pelvic pain syndrome as they rated spontaneous pain inside the scanner. Group differences (16 patients per group) in gray matter total volume and regional density were evaluated using voxel-based morphometry, and white matter integrity was studied with diffusion tensor imaging to measure fractional anisotropy. Functional and anatomical imaging outcomes were correlated with the clinical characteristics of chronic prostatitis/chronic pelvic pain syndrome.

Results: Spontaneous pelvic pain was uniquely characterized by functional activation within the right anterior insula, which correlated with clinical pain intensity. No group differences were found in regional gray matter volume, yet density of gray matter in pain relevant regions (anterior insula and anterior cingulate cortices) positively correlated with pain intensity and extent of pain chronicity. Moreover the correlation between white matter anisotropy and neocortical gray matter volume was disrupted in chronic prostatitis/chronic pelvic pain syndrome.

Conclusions: We provide novel evidence that the pain of chronic prostatitis/chronic pelvic pain syndrome is associated with a chronic pelvic pain syndrome specific pattern of functional brain activation and brain anatomical reorganization. These findings necessitate further investigations into the role of central mechanisms in the initiation and maintenance of chronic prostatitis/chronic pelvic pain syndrome.

Figure 1

Spontaneous pain rating task in patients with CP/CPPS. A, patients used finger-span logging device to continuously rate fluctuations in spontaneous pelvic pain (in absence of external stimulus) on scale from 0 to 10 by opening and closing fingers. B, inside scanner patients received feedback of pain ratings in real time, presented as visual bar projected onto screen that fluctuated on scale from 0 to 10. C, examples of spontaneous pain ratings from 3 patients with CP/CPPS. Individual patients exhibited distinct overall pain magnitudes and varying levels of fluctuations around mean spontaneous pain. Ratings were used as explanatory variables in fMRI analyses to identify related brain activity.

Figure 2

Group brain activity maps for spontaneous pain and visual rating tasks in CP/CPPS. A, group average brain activity for spontaneous pain rating task and for visual rating task. B, contrast between pain and visual tasks shows areas that were more specifically active during spontaneous pain of CP/CPPS (red-yellow), and included right anterior insula and parietal regions. Regions with higher activity during visual task (visual – pain) are shown as negative activity (blue-green).

Figure 3

Anterior insula activity is related to CP/CPPS pain intensity. A, peak activity from anterior insula (blue circle) identified from pain – visual contrast shows significantly larger activity in pain task vs visual task (bar graph), and shows significant positive relationship between activity and CP/CPPS pain intensity (each symbol is individual subject in scatterplot). B, correlation of peak activity from anterior insula with clinical parameters of CP/CPPS. In addition to spontaneous pain intensity MPQ exhibited significant correlation with insular activity.

Figure 4

Distinct regional gray matter densities reflect different clinical parameters of CP/CPPS. A, whole brain covariate map of voxel-wise gray matter density and pain intensity in patients with CP/CPPS shows positively correlated regions. Right anterior insula was main region identified (ant insula, blue circle) and further analyzed (bar graph and scatterplot). Peak right anterior insula gray matter density shows no difference between patients with CP/CPPS and healthy controls (bar graph), and significant positive correlation between density and pain intensity in patients with CP/CPPS (scatterplot). VAS, visual analog scale. ns, not significant. B, whole brain covariate map of voxel-wise gray matter density and pain duration (in log units) shows regions positively correlated with pain chronicity, identifying mainly anterior cingulate cortex (blue circle). Bar graph shows no difference for peak ACC gray matter density between patients with CP/CPPS and healthy controls. Scatterplot depicts significant positive correlation between ACC density and pain chronicity in patients with CP/CPPS.

Figure 5

Relationship between whole brain gray matter volume and white matter anisotropy is disrupted in patients with CP/CPPS. A, bar graph shows no difference in total neocortical gray matter volume (cc) between patients with CP/CPPS and controls. Scatterplots show degree of association between gray matter volume and age for controls (solid triangles) and patients (open circles). Both groups exhibited equivalent significant negative correlations between gray matter volume and age. B, bar graph shows no difference in mean whole brain white matter FA between patients with CP/CPPS and controls. Scatterplots show divergent correlations between whole brain FA and total gray matter volume (corrected for age). Whereas significant positive association between these parameters was found in healthy controls, relationship is absent in patients with CP/CPPS.