Pelvic tenderness is not limited to the prostate in chronic prostatitis/chronic pelvic pain syndrome (CPPS) type IIIA and IIIB: comparison of men with and without CP/CPPS

Idiopathic prostatitis (also called non-bacterial prostatitis) and prostatodynia have been renamed by a National Institutes of Health (NIH) consensus panel to Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) Types IIIA and IIIB, respectively. These syndromes are characterized by pelvic pain, a negative prostatic localization culture, and no specific diagnosis accounting for the pain. Voiding symptoms may or may not be present. Type IIIA is differentiated by leukocytes in the expressed prostatic secretions (EPS) and Type IIIB is characterized by a lack of inflammation in the EPS [1]. Recently, a large multicenter study found that the symptoms of prostatitis were not associated with prostatic inflammation, casting doubt on prostatic inflammation as the direct cause of the pain[2].

Pelvic tenderness has not been investigated in normal men. In CP/CPPS, tenderness of the prostate is often present [3, 4], however its relationship to prostatic inflammation has not been investigated. Whether pain is localized to the prostate or is part of a more generalized tenderness has not been determined.

The quantification of tenderness is difficult and subject to considerable inter-rater variability[5, 6]. However, tenderness is extremely important in everyday clinical evaluation and is routinely used to identify pathological processes. The American College of Rheumatology has developed The Manual Tender Point Survey (MTPS) as a standardized method to evaluate fibromyalgia (FM)[7]. This instrument includes 18 examination points that are often tender and 3 control points that are infrequently tender in patients with FM. Fibromyalgia (FM)is distinguished by multiple tender sites and pain in four quadrants of the body[8]. Patients with interstitial cystitis (IC), a condition that may be related to CP/CPPS, have been found to have increased tenderness in the pelvis and and in the MTPS as compared with patients without IC[9]. The purpose of this study was to use the MTPS, expanded to include pelvic tender points, to test the hypothesis that men with CP/CPPS would show more overall tenderness than men without pelvic pain. We hypothesized that the location of tenderness in CP/CPPS may indicate the location of underlying pathology and the extent of the tenderness may indicate a localized or more systemic nature of the syndrome. We explored the relationship of prostatic secretion inflammation to tenderness. A finding of an association between prostatic inflammation and prostatic tenderness would support the possibility that inflammation produces tenderness and pain. More muscle tenderness in men with CP/CPPS IIIB than in men with CP/CPPS IIIA, as suggested by Segura[10], would support the continued distinction between the two syndromes. We also hypothesized that there would be a relationship between tenderness and CPSI scores.

Seventy-two men with CP/CPPS and 98 controls were enrolled as part of a larger study[11‐16]. The tender points examination was instituted after the first 10 CP/CPPS subjects. Therefore, the present report is based on 62 CP/CPPS subjects and 98 controls. Patients and controls differed significantly on age (p < 0.001), education (p < 0.001), and employment status (p = 0.02), but not on race (p = 0.50) and marital status (p = 0.09) (Table 2). Among the CP/CPPS patients, 40.3% were Type IIIA, 18.1% Type IIIB, and 41.7% had undetermined type because EPS could not be obtained. Among controls, 38.8% had leukocyte counts > 500/mm³and 26.5% = 500/mm³, and EPS was not obtained for 34.7%. Subjects who the examiner was able to obtain EPS did not differ demographically from those in whom the examiner was unable to obtain EPS.

The proportion of subjects in the higher category of pain level for each tenderness site is shown in Table 3. Except for the control sites for tenderness, the pain group had consistently larger proportions of subjects with high scores than the control group. For example, 28.7% of the controls and 67.3% of the pain patients had high scores (as defined in Table 1) for IPTPS. Tenderness was found on prostate examination in 28 of 94 (29.8%) controls and 31 of 54 (57.4%) CP/CPPS patients.

To study the difference in proportions adjusting for clinicians, the dichotomized variables (low versus high level of pain) were analyzed using the Mantel-Haenzel method (Table 4). Pain patients were more likely than control subjects to be in the higher category of pain level for EPTPS, IPTPS, and prostate severity scores (odds ratios = 9.59, 6.25, and 4.98; p < 0.0001 for all), but not for the control site score (p = 0.98). There was a trend towards higher odds of pain patients being in the higher pain category for the MTPS tender points score (p = 0.069). When we examined dichotomized pain scores every point tested in the pelvis was more often painful in CPPS patients than controls except the suprapubic point. Relative ratios of painful points in CPPS patients to controls were highest in the mid perineum at 5.9. Most other ratios were 2–3. (Fig 1)

The second approach used the originally observed scores without dichotomization. In comparisons of the median scale scores of the patient and control groups for each examiner, there were statistically significant differences for all scales except the control sites (Table 5). For examiner 1, there were no statistically significant differences, although there were trends towards significant differences on the IPTPS and prostate scales, most likely because this clinician saw the smallest number of pain patients and controls.

Additionally, Spearman correlation was calculated for the tenderness points scores and the NIH CPSI for the pain patients. All tender point scales were statistically significant at 0.001 level, varying from estimated correlations of r = 0.29 (IPTPS and Control) to 0.73 (IPTPS with prostate score). The NIH CPSI Pain scale was correlated significantly with the FM and EPTPS, but not the IPTPS or prostate score suggesting that the CPSI pain score is more related to external than internal tenderness. However, plots of NIH CPSI versus each scale (graphs not shown here), showed that the associations are not necessarily linear, and therefore, they have limited value in describing the association between the variables.

EPS was obtained for 64 controls and 40 patients. Inflammation was defined as having leukocyte counts > 500/mm³ in the EPS sample. There was no association between inflammation in EPS and the dichotomous prostatic tenderness (p = 0.42) or FM, IPTPS, and EPTPS dichotomous variables (all p-values > 0.23).

Prostatic tenderness has been described in men with prostatitis and CP/CPPS and is considered to be a characteristic of both CP/CPPS Type IIIA and IIIB[4]. However, the findings of this study indicate that not all men with CP/CPPS have prostate tenderness, and about 30% of men without CP/CPPS have such tenderness. Tenderness in the internal and external pelvis as well as extra-pelvic regions in men with CP/CPPS has not been described. To our knowledge, this is the first study that has demonstrated that men with CP/CPPS have increased tenderness in FM tender points and in specific internal and external non-prostatic pelvic locations. For example, men with CP/CPPS were 9.59 and 4.98 times more likely than men without pelvic pain to have scores in the higher 90% of the EPTPS and prostate scales, respectively. This suggests that CP/CPPS Type III is a pan-pelvic pain syndrome and that tenderness is not limited to the prostate. For each point in the pelvis that we tested, the CPPS group had more tenderness than the control group. Furthermore, increased tenderness even extended outside of the pelvis to FM points suggesting a systemic component. The labeling of chronic pelvic pain in men as "prostatitis" may well mislead both patients and physicians into thinking that the syndrome has a more limited focus and etiology than it actually may have[20].

The finding of increased tenderness in MTPS tender points in men with CP/CPPS is in accord with findings of diffusely increased tenderness in women with interstitial cystitis, a syndrome possibly related to CP/CPPS[9]. We hypothesize that central and/or peripheral pain sensitization in the pelvis may account for the diffuse symptoms and tenderness found in pelvic pain syndromes[21‐25]. We have previously shown that there is sensitization to perineal heat sensation in some men with CP/CPPS[12, 26] and that men with CP/CPPS often have abnormalities of pelvic and abdominal muscular function and sensation [13]. The diffuse tenderness on pelvic examination in our present study may be a manifestation of mechanical sensitization to pressure with the development of allodynia and hyperesthesia mediated via the CNS. If prostatic inflammation was the source of prostatic pain and the non-prostate pelvic tenderness was secondary to muscle guarding, we would have expected to find a relationship of prostatic secretion inflammation to prostatic and muscle tenderness. Since we found no such associations, we hypothesize that prostatic and other pelvic tenderness may both be related to an another more dominant process such as central or peripheral neural sensitization and that inflammation in prostatic secretion may be incidental.

Limitations of this study should be acknowledged. The sample came from a university tertiary care population and the study findings may not generalize to other populations. The control group was a convenience sample of volunteers and could have selection bias. Controls were younger, and although we found no relationship of tenderness scores to age, other unknown differences may have contributed to the differences found between patients and controls in examination findings. Furthermore, we did not assess test-retest stability of the tender point examination scores, and there were interrater differences. The determination of tenderness is a standard part of clinical examination, although variation from examiner to examiner is well known clinically and experimentally[5, 6]. Although some of our examiners consistently found more tenderness, each examiner separately found more tenderness in CPPS patients in the areas examined.

We found that men with CP/CPPS have generalized internal and external pelvic tenderness. The pathophysiology of CP/CPPS involves the entire pelvis and not only the prostate. Our findings suggest that further research involving the assessment of intra-and extra-pelvic tender points may prove fruitful in increasing scientific understanding of, and developing more effective treatments for, male chronic pelvic pain syndromes.