- Email: [email protected]
The Impact of Neuropathic Pain in the Chronic Pelvic Pain Population
The Impact of Neuropathic Pain in the Chronic Pelvic Pain Population Arvin K. George,* Mostafa A. Sadek, Sandeep S. Saluja, Jennifer Y. Fariello, Kristene E. Whitmore† and Robert M. Moldwin‡ From the Arthur Smith Institute for Urology, Hofstra North Shore-Long Island Jewish School of Medicine, New Hyde Park, New York, and Pelvic and Sexual Health Institute (JYF, KEW), Philadelphia, Pennsylvania
Purpose: Patients with chronic pelvic pain disorders often present with neuropathic features. We examined a cohort of patients with a primary complaint of chronic pelvic pain for the presence of neuropathic pain symptoms. Materials and Methods: Patients with chronic pelvic pain disorders from 2 tertiary referral centers were prospectively evaluated. The validated S-LANSS (Self-Administered Leeds Assessment of Neuropathic Symptoms and Signs) survey was used to examine pain symptoms of neuropathic origin. Patients completed SF-12v2™ to assess mental/physical health domains. The 2-tailed t test and chi-square analysis were used to compare physical and mental component summaries in patients with vs without neuropathic symptoms. Results: A total of 142 patients mean age of 45 years were included in analysis. Of the patients 72.5% with chronic pelvic pain carried more than 1 primary diagnosis. The S-LANSS survey identified symptoms suggestive of neuropathic pain in 44 patients (31%). A greater proportion of patients with a neuropathic component had altered sensation in the affected area (86.4% vs 24.5%). Patients with neuropathic pain scored 4.28 and 5.45 points lower on the physical and mental component summaries (p ⫽ 0.053 and 0.008, respectively). Conclusions: A large proportion of patients with chronic pelvic pain present with neuropathic features and report decreased quality of life compared with the general population. Those with neuropathic symptoms have significantly lower quality of life than those without such symptoms. Clinicians can identify patients to use targeted therapies and use a multidisciplinary approach to care.
Abbreviations and Acronyms CPP ⫽ chronic pelvic pain HRQOL ⫽ health related quality of life MCS ⫽ mental component summary PCS ⫽ physical component summary Submitted for publication March 5, 2012. Study received institutional review board approval. * Correspondence: Arthur Smith Institute for Urology, Hofstra North Shore-Long Island Jewish School of Medicine, 450 Lakeville Rd., Suite M-41, New Hyde Park, New York 11040 (telephone: 516-734-8500; FAX: 516-734-8537; e-mail: [email protected]). † Financial interest and/or other relationship with American Urological Association, BSCT, Pfizer and Allergan. ‡ Financial interest and/or other relationship with Taris, Janssen and Pfizer.
Key Words: urinary bladder; cystitis, interstitial; pain; nerves; quality of life CHRONIC pelvic pain manifests as various pathological conditions, ranging from vulvodynia to chronic prostatitis. Its various clinical presentations likely represent a spectrum of disease rather than distinct clinical entities. The pathophysiology of individual diagnoses is also multifactorial and poorly understood. Challenges in diagnosis and management have prompted greater research on strategies to identify and treat these patients since current ther-
apeutic options are still aimed at symptomatic relief. The Special Interest Group on Neuropathic Pain of the International Association for the Study of Pain defines neuropathic pain as pain arising as a direct consequence of a lesion or disease that affects the sensory component of the nervous system. Growing evidence supports a neuropathic component to chronic pelvic pain syndromes. Neuromodulating agents, in-
0022-5347/12/1885-1783/0 THE JOURNAL OF UROLOGY® © 2012 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
http://dx.doi.org/10.1016/j.juro.2012.07.034 Vol. 188, 1783-1787, November 2012 RESEARCH, INC. Printed in U.S.A.
AND
www.jurology.com
1783
1784
IMPACT OF NEUROPATHIC PAIN IN CHRONIC PELVIC PAIN POPULATION
cluding tricyclic antidepressants and anticonvulsants, are often used to control symptoms. Nerve growth factor in seminal plasma and expressed prostatic secretions are potential biomarkers that correlate with pain severity and treatment response in men with chronic prostatitis/chronic pelvic pain syndrome.1,2 It was proposed that neuropathic pain is not binary but rather lies on a spectrum with pain that is more or less neuropathic in origin. This impression contributes to the diagnostic challenge facing clinicians. Correctly categorizing patients with a central source of visceral complaints would identify those who may benefit most from targeted therapeutic regimens. Chronic pelvic pain can be severe and disabling in affected patients but there has been little effort to objectively quantify its effect on quality of life. Quality of life data provide the added advantage of an objective evaluation before and after treatment by monitoring change in specific HRQOL domains. Patients with neuropathic pain as a result of failed back surgery, diabetic neuropathy and post-herpetic neuralgia reported substantially lower HRQOL than the general population and neuropathic pain severity emerged as a primary predictor of the negative health impact in a recent systematic review.3,4 If physicians could correctly identify patients with a neuropathic pain component, they could offer directed therapies to patients with a limited response to conventional treatments, while at the same time targeting those at greatest risk for decreased HRQOL.
METHODS A total of 142 consecutive patients with CPP disorders from 2 tertiary referral centers were prospectively evaluated. The primary diagnosis was recorded after comprehensive history and physical examination. Interstitial cystitis was defined according to the European Society for the Study of BPS.5 Patients with chronic (greater than 6 months) pelvic pain, pressure or discomfort perceived to be related to the bladder, which was accompanied by at least 1 other urinary symptom such as persistent urge to void or frequency, were included in the study. Pelvic floor dysfunction was defined as chronic pelvic pain associated with hypertonicity or tenderness to palpation of the pelvic floor musculature.6 Individuals diagnosed with provoked vestibulodynia, generalized vulvodynia and vulvar vestibulitis syndrome were combined into 1 group with vulvar disorders. Provoked vestibulodynia was defined as pain upon touch or physical contact of the vestibular area of the vulva. Generalized vulvodynia was characterized by chronic vulvar itching, burning and/or pain that cause physical, sexual and psychological distress. Vulvar vestibulitis syndrome was defined as severe pain during attempted vaginal entry, tenderness to pressure localized to the vulvar vestibule and redness of the vulvar vestibule. The validated S-LANSS was used to examine pain symptoms primarily of neuropathic origin.7,8 The S-LANSS
pain score was determined by patient completion of the 7-question survey, including 5 questions on the quality and character of pain symptoms, and 2 instructing participants to perform self-examinations to determine allodynia and altered sensation. An S-LANSS score of 12 or greater was determined to indicate pain primarily neuropathic in origin. The chi-square test and contingency tables were used to assess differences in symptoms between the groups. A bivariate regression model was applied to compare S-LANSS score and primary diagnosis. Quality of life scores were derived from administration of the SF-12v2 Health Survey to assess 8 domains, resulting in a summary of respondent health status from broad physical and mental health perspectives. The 2-tailed t test was used to analyze SF-12v2 PCS and MCS in patients with CPP with and without neuropathic features. Component summaries were also compared to historical data collected from the general population to determine differences in quality of life among patients with and without CPP.
RESULTS A total of 142 patients with a mean age of 45 years (range 14 to 82) were included in the study. Participants were predominantly female (132 of 142 or 93%) and only 10 (7%) were male. Of the patients 90 (63%) carried a diagnosis of interstitial cystitis, 117 (82%) were diagnosed with pelvic floor dysfunction and 83 (59%) were determined to have a vulvar disorder including provoked vestibulodynia, generalized vulvodynia or vulvar vestibulitis syndrome. Of the 142 patients 103 (72.5%) met the criteria for more than 1 primary diagnosis, confirming that multiple factors contributed to CPP disorders. On a scale of 1 to 10 the mean visual analog pain score was significantly greater in patients deemed to have neuropathic pain by S-LANSS (6.2 vs 4.5, p ⬍0.001). Scores S-LANSS. Of the patients 44 (31%) had a score of 12 or greater and, thus, were determined to have a neuropathic component to symptoms (see table). The mean total score of those with vs without a neuropathic component was 16.2 vs 3.9. Hypersensitivity and altered sensation were the most evident findings in the affected areas when comparing the 2 groups. Of those found to have neuropathic pain 86.4% (38 of 44) complained of the painful area being abnormally sensitive to touch vs 24.5% (24 of 98) of those without allodynia or neuropathic pain (p ⬍0.001). On self-examination 88.6% of patients (39 of 44) with a score of 12 or greater reported pins and needles, tingling and burning in the painful area compared to a nonpainful area and 95.5% (42 of 44) reported numbness or tenderness. Alternatively, 19.4% (19 of 98) and 39.8% (39 of 98) of those with a score of less than 12 reported such findings in the
IMPACT OF NEUROPATHIC PAIN IN CHRONIC PELVIC PAIN POPULATION
1785
S-LANSS scores in patients with CPP % S-LANSS Score (No. pts)*
Overall Pins/needles Color change with increased pain Sensitivity to touch Sudden/burst of pain Burning pain/hot to touch Pins/needles on rubbing self-examination Altered sensation with pressure
Less Than 12
12 or Greater
p Value
69 (98) 7.1 (7) 4.1 (4) 24.5 (24) 20.4 (20) 16.3 (16) 19.4 (19)
31 (44) 47.7 (21) 52.3 (23) 86.4 (38) 47.7 (21) 72.7 (32) 88.6 (39)
⬍0.0001 ⬍0.0001 ⬍0.0001 0.0013 ⬍0.0001 ⬍0.0001
39.8 (39)
95.5 (42)
⬍0.0001
* Mean score was 3.9 and 16.2 in those with score less than 12 and 12 or greater, respectively (p ⬍0.0001).
corresponding questions requiring patient self-examination (p ⬍0.001). Figure 1 shows the bivariate regression model. Patients with interstitial cystitis (OR 1.05), pelvic floor dysfunction (OR 1.42) and vulvar disorders (OR 1.42) had an increased likelihood of a neuropathic pain component. Patients carrying more than 1 diagnosis were twice as likely to have a neuropathic pain component (OR 1.98). There was a neuropathic component in 28 of 90 patients (31.1%) with interstitial cystitis, 37 of 117 (31.6%) with a pelvic floor disorder and 32 of 83 (38.6%) with vulvodynia, although 10 carried more than 1 diagnosis. SF-12v2. For the entire cohort mean MCS and PCS scores were 43.5 and 45.1, respectively, which was 11.4 points below the combined average for the American population (fig. 2). Patients with a significant neuropathic pain component scored 4.28 points lower on the PCS (p ⫽ 0.053) and 5.45 points lower on the MCS (p ⫽ 0.008) than patients with CPP without neuropathic pain. Only 2.8% of those without neuropathic pain and 11.1% with neuropathic pain rated overall health as poor (p ⫽ 0.048). Pa-
Figure 1. Bivariate regression model of pelvic pain diagnosis and presence of neuropathic pain.
Figure 2. CPP PCS and MCS with (blue bars) and without (red bars) neuropathic pain. Green bars represent average, normal American population.
tients with neuropathic pain stated that they were more often limited in activity types due to physical health compared to those without neuropathic pain (60.0% vs 46.3%, p ⫽ 0.172). The greatest differences in the groups were seen in the MCS. Of the patients 73.9% vs 40% limited social activities due to physical health or emotional problems (p ⫽ 0.008). Additionally, a larger proportion of patients with neuropathic pain relayed a depressed mood than their nonneuropathic counterparts, although this difference did not attain statistical significance (48.9% vs 36.1%, p ⫽ 0.197).
DISCUSSION Patients with CPP present a diagnostic and therapeutic challenge to the clinicians responsible for care. The multifactorial nature of the illness makes it difficult to achieve similar success rates with standardized regimens and, consequently, treatment must be individualized to the patient symptom profile. Although a neuropathic component in CPP syndromes is widely accepted, only recently has there been a growing body of evidence to support this notion. Neuromodulating agents, including tricyclic antidepressants and serotonin/norepinephrine reuptake inhibitors, are in the traditional armamentarium. However, patient selection for specific medications may often be nonspecific and a patient may be selected only if unresponsive to alternative options. It remains a priority to discover novel approaches to accurately distinguish those who may benefit from available treatments.
1786
IMPACT OF NEUROPATHIC PAIN IN CHRONIC PELVIC PAIN POPULATION
S-LANSS is a self-administered tool consisting of a 5-item questionnaire on pain symptoms and a 2-item self-examination portion to determine allodynia and altered sensation. Responses are binary and weighted differently according to the OR of an affirmative response predicting that pain is primarily neuropathic in origin. The score is calculated from a possible maximum of 24 with a score of 12 or greater suggestive of neuropathic pain. S-LANSS was validated and found to have 74% sensitivity and 76% specificity when subjects from a chronic pain practice completed the questionnaire unaided.6 As a screening tool for neuropathic pain in the general population, it has been 94% sensitive and 91% specific. It is recommended as an assessment tool by the Special Interest Group on Neuropathic Pain and the European Federation of Neurological Societies. A significant advantage of S-LANSS is its ease of administration since it can be completed during patient intake or comprehensive history within 2 minutes. Our study revealed the high prevalence of neuropathic symptoms in the CPP population with almost 1 of 3 patients reporting a score of 12 or greater on S-LANSS. This group of patients overwhelmingly presented with hypersensitivity and altered sensation compared with the group thought to have primarily nociceptive pain. Additionally, those with neuropathic pain did not have an increased incidence of an attributable anatomical abnormality, such as disk herniation. Results of a randomized, controlled trial by the Chronic Prostatitis Collaborative Research Network-2 demonstrated that pregabalin therapy for 6 weeks was not superior to placebo in the rate of a 6-point decrease in the National Institutes of Health Chronic Prostatitis Symptom Index.9 However, men assigned to pregabalin experienced decreased total scores and subscores.9 Pregabalin is approved for the chronic pain of post-herpetic neuralgia, diabetic neuropathy and fibromyalgia. A decrease in the total score suggests a possible benefit in this patient cohort that could be highlighted if patients were stratified into those with and without a predominantly neuropathic component.
The SF-12v2 Health Survey is a valid, reliable, self-reported measure of patient functional health.10 SF-12v2 uses 1 or 2 items covering 8 health domains and produces a psychometrically based PCS and MCS. SF-12v2 has been used as a measure of overall health and HRQOL in multiple studies for specific disease states. Patients with chronic neuropathic pain identified by S-LANSS have shown significant differences in all SF-36 domains even when controlling for pain severity, age and gender, indicating poorer health and greater disability.11 Limited data currently exist on HRQOL in CPP cases. To our knowledge this report represents the only study showing the difference between neuropathic and nonneuropathic symptoms in the CPP population. Overall, mean MCS and PCS scores were 43.5 and 45.1, respectively. Differences were clearly seen for MCS with patients with vs without neuropathy scoring 41 vs 47. The significant decreases in PCS in patients with a neuropathic component are similar to findings in those with chronic renal insufficiency not requiring dialysis, although MCS scores in each group were lower than in patients with end stage renal disease on hemodialysis.12 Additionally, MCS scores in patients with a neuropathic component were comparable to scores in patients with severe chronic obstructive pulmonary disease and congestive heart failure.13,14 The limitations of our study include the inherent bias associated with self-reported data. Patients presenting to the physician office complete surveys based on symptoms at the time of completion. Additionally, S-LANSS completion includes self-examination and interpretation of symptoms, which can induce a small degree of variability.
CONCLUSIONS A third of patients with CPP present with neuropathic features and report decreased quality of life compared with the general population. These results compel health care providers to actively discriminate among patients with neuropathic symptoms and stress the importance of a multidisciplinary approach to care addressing the impact of CPP on patient mental health.
REFERENCES 1. Miller LJ, Fischer KA, Goralnick SJ et al: Nerve growth factor and chronic prostatitis/chronic pelvic pain syndrome. Urology 2002; 59: 603. 2. Watanabe T, Inoue M, Sasaki K et al: Nerve growth factor level in the prostatic fluid of patients with chronic prostatitis/chronic pelvic pain
syndrome is correlated with symptom severity and response to treatment. BJU Int 2010; 108: 248. 3. Jensen MP, Chodroff MJ and Dworkin RH: The impact of neuropathic pain on health-related quality of life: review and implications. Neurology 2007; 28: 1178.
4. Doth AH, Hansson PT, Jensen MP et al: The burden of neuropathic pain: a systematic review and meta-analysis of health utilities. Pain 2010; 149: 338. 5. van de Merwe JP, Nordling J, Bouchelouche P et al: Diagnostic criteria, classification, and nomenclature for painful bladder syndrome/
IMPACT OF NEUROPATHIC PAIN IN CHRONIC PELVIC PAIN POPULATION
interstitial cystitis: an ESSIC proposal. Eur Urol 2008; 53: 60. 6. Srinivasan AK, Kaye JD and Moldwin RM: Myofascial dysfunction associated with chronic pelvic floor pain: management strategies. Curr Pain Headache Rep 2007; 11: 359. 7. Weingarten TN, Watson JC, Hooten WM et al: Validation of the S-LANSS in the community setting. Pain 2007; 132: 189. 8. Bennett MI, Smith BH, Torrance N et al: The S-LANSS score for identifying pain of predominantly neuropathic origin: validation for use in clinical and postal research. J Pain 2005; 6: 149.
1787
9. Pontari MA, Krieger JN and Litwin MS: Pregabalin for the treatment of men with chronic prostatitis/chronic pelvic pain syndrome. Arch Intern Med 2010; 170: 1586.
12. Gorodetskaya I, Zenios S, McCulloch CE et al: Health-related quality of life and estimates of utility in chronic kidney disease. Kidney Int 2005: 68: 2801.
10. Ware J Jr, Kosinski M and Keller SD: A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med Care 1996; 34: 220.
13. Carrasco Garrido P, de Miguel Diez J, Rejas Gutierrez J et al: Negative impact of chronic obstructive pulmonary disease on the health-related quality of life of patients. Results of the EPIDEPOC study. Health Qual Life Outcomes 2006; 4: 31.
11. Smith BH, Torrance N, Bennett MI et al: Health and quality of life associated with chronic pain of predominantly neuropathic origin in the community. Clin J Pain 2007; 23: 143.
14. Smolderen KG, Pelle AJ, Kupper N et al: Impact of peripheral arterial disease on health status: a comparison with chronic heart failure. J Vasc Surg 2009; 50: 1391.
Purpose: Patients with chronic pelvic pain disorders often present with neuropathic features. We examined a cohort of patients with a primary complaint of chronic pelvic pain for the presence of neuropathic pain symptoms. Materials and Methods: Patients with chronic pelvic pain disorders from 2 tertiary referral centers were prospectively evaluated. The validated S-LANSS (Self-Administered Leeds Assessment of Neuropathic Symptoms and Signs) survey was used to examine pain symptoms of neuropathic origin. Patients completed SF-12v2™ to assess mental/physical health domains. The 2-tailed t test and chi-square analysis were used to compare physical and mental component summaries in patients with vs without neuropathic symptoms. Results: A total of 142 patients mean age of 45 years were included in analysis. Of the patients 72.5% with chronic pelvic pain carried more than 1 primary diagnosis. The S-LANSS survey identified symptoms suggestive of neuropathic pain in 44 patients (31%). A greater proportion of patients with a neuropathic component had altered sensation in the affected area (86.4% vs 24.5%). Patients with neuropathic pain scored 4.28 and 5.45 points lower on the physical and mental component summaries (p ⫽ 0.053 and 0.008, respectively). Conclusions: A large proportion of patients with chronic pelvic pain present with neuropathic features and report decreased quality of life compared with the general population. Those with neuropathic symptoms have significantly lower quality of life than those without such symptoms. Clinicians can identify patients to use targeted therapies and use a multidisciplinary approach to care.
Abbreviations and Acronyms CPP ⫽ chronic pelvic pain HRQOL ⫽ health related quality of life MCS ⫽ mental component summary PCS ⫽ physical component summary Submitted for publication March 5, 2012. Study received institutional review board approval. * Correspondence: Arthur Smith Institute for Urology, Hofstra North Shore-Long Island Jewish School of Medicine, 450 Lakeville Rd., Suite M-41, New Hyde Park, New York 11040 (telephone: 516-734-8500; FAX: 516-734-8537; e-mail: [email protected]). † Financial interest and/or other relationship with American Urological Association, BSCT, Pfizer and Allergan. ‡ Financial interest and/or other relationship with Taris, Janssen and Pfizer.
Key Words: urinary bladder; cystitis, interstitial; pain; nerves; quality of life CHRONIC pelvic pain manifests as various pathological conditions, ranging from vulvodynia to chronic prostatitis. Its various clinical presentations likely represent a spectrum of disease rather than distinct clinical entities. The pathophysiology of individual diagnoses is also multifactorial and poorly understood. Challenges in diagnosis and management have prompted greater research on strategies to identify and treat these patients since current ther-
apeutic options are still aimed at symptomatic relief. The Special Interest Group on Neuropathic Pain of the International Association for the Study of Pain defines neuropathic pain as pain arising as a direct consequence of a lesion or disease that affects the sensory component of the nervous system. Growing evidence supports a neuropathic component to chronic pelvic pain syndromes. Neuromodulating agents, in-
0022-5347/12/1885-1783/0 THE JOURNAL OF UROLOGY® © 2012 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
http://dx.doi.org/10.1016/j.juro.2012.07.034 Vol. 188, 1783-1787, November 2012 RESEARCH, INC. Printed in U.S.A.
AND
www.jurology.com
1783
1784
IMPACT OF NEUROPATHIC PAIN IN CHRONIC PELVIC PAIN POPULATION
cluding tricyclic antidepressants and anticonvulsants, are often used to control symptoms. Nerve growth factor in seminal plasma and expressed prostatic secretions are potential biomarkers that correlate with pain severity and treatment response in men with chronic prostatitis/chronic pelvic pain syndrome.1,2 It was proposed that neuropathic pain is not binary but rather lies on a spectrum with pain that is more or less neuropathic in origin. This impression contributes to the diagnostic challenge facing clinicians. Correctly categorizing patients with a central source of visceral complaints would identify those who may benefit most from targeted therapeutic regimens. Chronic pelvic pain can be severe and disabling in affected patients but there has been little effort to objectively quantify its effect on quality of life. Quality of life data provide the added advantage of an objective evaluation before and after treatment by monitoring change in specific HRQOL domains. Patients with neuropathic pain as a result of failed back surgery, diabetic neuropathy and post-herpetic neuralgia reported substantially lower HRQOL than the general population and neuropathic pain severity emerged as a primary predictor of the negative health impact in a recent systematic review.3,4 If physicians could correctly identify patients with a neuropathic pain component, they could offer directed therapies to patients with a limited response to conventional treatments, while at the same time targeting those at greatest risk for decreased HRQOL.
METHODS A total of 142 consecutive patients with CPP disorders from 2 tertiary referral centers were prospectively evaluated. The primary diagnosis was recorded after comprehensive history and physical examination. Interstitial cystitis was defined according to the European Society for the Study of BPS.5 Patients with chronic (greater than 6 months) pelvic pain, pressure or discomfort perceived to be related to the bladder, which was accompanied by at least 1 other urinary symptom such as persistent urge to void or frequency, were included in the study. Pelvic floor dysfunction was defined as chronic pelvic pain associated with hypertonicity or tenderness to palpation of the pelvic floor musculature.6 Individuals diagnosed with provoked vestibulodynia, generalized vulvodynia and vulvar vestibulitis syndrome were combined into 1 group with vulvar disorders. Provoked vestibulodynia was defined as pain upon touch or physical contact of the vestibular area of the vulva. Generalized vulvodynia was characterized by chronic vulvar itching, burning and/or pain that cause physical, sexual and psychological distress. Vulvar vestibulitis syndrome was defined as severe pain during attempted vaginal entry, tenderness to pressure localized to the vulvar vestibule and redness of the vulvar vestibule. The validated S-LANSS was used to examine pain symptoms primarily of neuropathic origin.7,8 The S-LANSS
pain score was determined by patient completion of the 7-question survey, including 5 questions on the quality and character of pain symptoms, and 2 instructing participants to perform self-examinations to determine allodynia and altered sensation. An S-LANSS score of 12 or greater was determined to indicate pain primarily neuropathic in origin. The chi-square test and contingency tables were used to assess differences in symptoms between the groups. A bivariate regression model was applied to compare S-LANSS score and primary diagnosis. Quality of life scores were derived from administration of the SF-12v2 Health Survey to assess 8 domains, resulting in a summary of respondent health status from broad physical and mental health perspectives. The 2-tailed t test was used to analyze SF-12v2 PCS and MCS in patients with CPP with and without neuropathic features. Component summaries were also compared to historical data collected from the general population to determine differences in quality of life among patients with and without CPP.
RESULTS A total of 142 patients with a mean age of 45 years (range 14 to 82) were included in the study. Participants were predominantly female (132 of 142 or 93%) and only 10 (7%) were male. Of the patients 90 (63%) carried a diagnosis of interstitial cystitis, 117 (82%) were diagnosed with pelvic floor dysfunction and 83 (59%) were determined to have a vulvar disorder including provoked vestibulodynia, generalized vulvodynia or vulvar vestibulitis syndrome. Of the 142 patients 103 (72.5%) met the criteria for more than 1 primary diagnosis, confirming that multiple factors contributed to CPP disorders. On a scale of 1 to 10 the mean visual analog pain score was significantly greater in patients deemed to have neuropathic pain by S-LANSS (6.2 vs 4.5, p ⬍0.001). Scores S-LANSS. Of the patients 44 (31%) had a score of 12 or greater and, thus, were determined to have a neuropathic component to symptoms (see table). The mean total score of those with vs without a neuropathic component was 16.2 vs 3.9. Hypersensitivity and altered sensation were the most evident findings in the affected areas when comparing the 2 groups. Of those found to have neuropathic pain 86.4% (38 of 44) complained of the painful area being abnormally sensitive to touch vs 24.5% (24 of 98) of those without allodynia or neuropathic pain (p ⬍0.001). On self-examination 88.6% of patients (39 of 44) with a score of 12 or greater reported pins and needles, tingling and burning in the painful area compared to a nonpainful area and 95.5% (42 of 44) reported numbness or tenderness. Alternatively, 19.4% (19 of 98) and 39.8% (39 of 98) of those with a score of less than 12 reported such findings in the
IMPACT OF NEUROPATHIC PAIN IN CHRONIC PELVIC PAIN POPULATION
1785
S-LANSS scores in patients with CPP % S-LANSS Score (No. pts)*
Overall Pins/needles Color change with increased pain Sensitivity to touch Sudden/burst of pain Burning pain/hot to touch Pins/needles on rubbing self-examination Altered sensation with pressure
Less Than 12
12 or Greater
p Value
69 (98) 7.1 (7) 4.1 (4) 24.5 (24) 20.4 (20) 16.3 (16) 19.4 (19)
31 (44) 47.7 (21) 52.3 (23) 86.4 (38) 47.7 (21) 72.7 (32) 88.6 (39)
⬍0.0001 ⬍0.0001 ⬍0.0001 0.0013 ⬍0.0001 ⬍0.0001
39.8 (39)
95.5 (42)
⬍0.0001
* Mean score was 3.9 and 16.2 in those with score less than 12 and 12 or greater, respectively (p ⬍0.0001).
corresponding questions requiring patient self-examination (p ⬍0.001). Figure 1 shows the bivariate regression model. Patients with interstitial cystitis (OR 1.05), pelvic floor dysfunction (OR 1.42) and vulvar disorders (OR 1.42) had an increased likelihood of a neuropathic pain component. Patients carrying more than 1 diagnosis were twice as likely to have a neuropathic pain component (OR 1.98). There was a neuropathic component in 28 of 90 patients (31.1%) with interstitial cystitis, 37 of 117 (31.6%) with a pelvic floor disorder and 32 of 83 (38.6%) with vulvodynia, although 10 carried more than 1 diagnosis. SF-12v2. For the entire cohort mean MCS and PCS scores were 43.5 and 45.1, respectively, which was 11.4 points below the combined average for the American population (fig. 2). Patients with a significant neuropathic pain component scored 4.28 points lower on the PCS (p ⫽ 0.053) and 5.45 points lower on the MCS (p ⫽ 0.008) than patients with CPP without neuropathic pain. Only 2.8% of those without neuropathic pain and 11.1% with neuropathic pain rated overall health as poor (p ⫽ 0.048). Pa-
Figure 1. Bivariate regression model of pelvic pain diagnosis and presence of neuropathic pain.
Figure 2. CPP PCS and MCS with (blue bars) and without (red bars) neuropathic pain. Green bars represent average, normal American population.
tients with neuropathic pain stated that they were more often limited in activity types due to physical health compared to those without neuropathic pain (60.0% vs 46.3%, p ⫽ 0.172). The greatest differences in the groups were seen in the MCS. Of the patients 73.9% vs 40% limited social activities due to physical health or emotional problems (p ⫽ 0.008). Additionally, a larger proportion of patients with neuropathic pain relayed a depressed mood than their nonneuropathic counterparts, although this difference did not attain statistical significance (48.9% vs 36.1%, p ⫽ 0.197).
DISCUSSION Patients with CPP present a diagnostic and therapeutic challenge to the clinicians responsible for care. The multifactorial nature of the illness makes it difficult to achieve similar success rates with standardized regimens and, consequently, treatment must be individualized to the patient symptom profile. Although a neuropathic component in CPP syndromes is widely accepted, only recently has there been a growing body of evidence to support this notion. Neuromodulating agents, including tricyclic antidepressants and serotonin/norepinephrine reuptake inhibitors, are in the traditional armamentarium. However, patient selection for specific medications may often be nonspecific and a patient may be selected only if unresponsive to alternative options. It remains a priority to discover novel approaches to accurately distinguish those who may benefit from available treatments.
1786
IMPACT OF NEUROPATHIC PAIN IN CHRONIC PELVIC PAIN POPULATION
S-LANSS is a self-administered tool consisting of a 5-item questionnaire on pain symptoms and a 2-item self-examination portion to determine allodynia and altered sensation. Responses are binary and weighted differently according to the OR of an affirmative response predicting that pain is primarily neuropathic in origin. The score is calculated from a possible maximum of 24 with a score of 12 or greater suggestive of neuropathic pain. S-LANSS was validated and found to have 74% sensitivity and 76% specificity when subjects from a chronic pain practice completed the questionnaire unaided.6 As a screening tool for neuropathic pain in the general population, it has been 94% sensitive and 91% specific. It is recommended as an assessment tool by the Special Interest Group on Neuropathic Pain and the European Federation of Neurological Societies. A significant advantage of S-LANSS is its ease of administration since it can be completed during patient intake or comprehensive history within 2 minutes. Our study revealed the high prevalence of neuropathic symptoms in the CPP population with almost 1 of 3 patients reporting a score of 12 or greater on S-LANSS. This group of patients overwhelmingly presented with hypersensitivity and altered sensation compared with the group thought to have primarily nociceptive pain. Additionally, those with neuropathic pain did not have an increased incidence of an attributable anatomical abnormality, such as disk herniation. Results of a randomized, controlled trial by the Chronic Prostatitis Collaborative Research Network-2 demonstrated that pregabalin therapy for 6 weeks was not superior to placebo in the rate of a 6-point decrease in the National Institutes of Health Chronic Prostatitis Symptom Index.9 However, men assigned to pregabalin experienced decreased total scores and subscores.9 Pregabalin is approved for the chronic pain of post-herpetic neuralgia, diabetic neuropathy and fibromyalgia. A decrease in the total score suggests a possible benefit in this patient cohort that could be highlighted if patients were stratified into those with and without a predominantly neuropathic component.
The SF-12v2 Health Survey is a valid, reliable, self-reported measure of patient functional health.10 SF-12v2 uses 1 or 2 items covering 8 health domains and produces a psychometrically based PCS and MCS. SF-12v2 has been used as a measure of overall health and HRQOL in multiple studies for specific disease states. Patients with chronic neuropathic pain identified by S-LANSS have shown significant differences in all SF-36 domains even when controlling for pain severity, age and gender, indicating poorer health and greater disability.11 Limited data currently exist on HRQOL in CPP cases. To our knowledge this report represents the only study showing the difference between neuropathic and nonneuropathic symptoms in the CPP population. Overall, mean MCS and PCS scores were 43.5 and 45.1, respectively. Differences were clearly seen for MCS with patients with vs without neuropathy scoring 41 vs 47. The significant decreases in PCS in patients with a neuropathic component are similar to findings in those with chronic renal insufficiency not requiring dialysis, although MCS scores in each group were lower than in patients with end stage renal disease on hemodialysis.12 Additionally, MCS scores in patients with a neuropathic component were comparable to scores in patients with severe chronic obstructive pulmonary disease and congestive heart failure.13,14 The limitations of our study include the inherent bias associated with self-reported data. Patients presenting to the physician office complete surveys based on symptoms at the time of completion. Additionally, S-LANSS completion includes self-examination and interpretation of symptoms, which can induce a small degree of variability.
CONCLUSIONS A third of patients with CPP present with neuropathic features and report decreased quality of life compared with the general population. These results compel health care providers to actively discriminate among patients with neuropathic symptoms and stress the importance of a multidisciplinary approach to care addressing the impact of CPP on patient mental health.
REFERENCES 1. Miller LJ, Fischer KA, Goralnick SJ et al: Nerve growth factor and chronic prostatitis/chronic pelvic pain syndrome. Urology 2002; 59: 603. 2. Watanabe T, Inoue M, Sasaki K et al: Nerve growth factor level in the prostatic fluid of patients with chronic prostatitis/chronic pelvic pain
syndrome is correlated with symptom severity and response to treatment. BJU Int 2010; 108: 248. 3. Jensen MP, Chodroff MJ and Dworkin RH: The impact of neuropathic pain on health-related quality of life: review and implications. Neurology 2007; 28: 1178.
4. Doth AH, Hansson PT, Jensen MP et al: The burden of neuropathic pain: a systematic review and meta-analysis of health utilities. Pain 2010; 149: 338. 5. van de Merwe JP, Nordling J, Bouchelouche P et al: Diagnostic criteria, classification, and nomenclature for painful bladder syndrome/
IMPACT OF NEUROPATHIC PAIN IN CHRONIC PELVIC PAIN POPULATION
interstitial cystitis: an ESSIC proposal. Eur Urol 2008; 53: 60. 6. Srinivasan AK, Kaye JD and Moldwin RM: Myofascial dysfunction associated with chronic pelvic floor pain: management strategies. Curr Pain Headache Rep 2007; 11: 359. 7. Weingarten TN, Watson JC, Hooten WM et al: Validation of the S-LANSS in the community setting. Pain 2007; 132: 189. 8. Bennett MI, Smith BH, Torrance N et al: The S-LANSS score for identifying pain of predominantly neuropathic origin: validation for use in clinical and postal research. J Pain 2005; 6: 149.
1787
9. Pontari MA, Krieger JN and Litwin MS: Pregabalin for the treatment of men with chronic prostatitis/chronic pelvic pain syndrome. Arch Intern Med 2010; 170: 1586.
12. Gorodetskaya I, Zenios S, McCulloch CE et al: Health-related quality of life and estimates of utility in chronic kidney disease. Kidney Int 2005: 68: 2801.
10. Ware J Jr, Kosinski M and Keller SD: A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med Care 1996; 34: 220.
13. Carrasco Garrido P, de Miguel Diez J, Rejas Gutierrez J et al: Negative impact of chronic obstructive pulmonary disease on the health-related quality of life of patients. Results of the EPIDEPOC study. Health Qual Life Outcomes 2006; 4: 31.
11. Smith BH, Torrance N, Bennett MI et al: Health and quality of life associated with chronic pain of predominantly neuropathic origin in the community. Clin J Pain 2007; 23: 143.
14. Smolderen KG, Pelle AJ, Kupper N et al: Impact of peripheral arterial disease on health status: a comparison with chronic heart failure. J Vasc Surg 2009; 50: 1391.