Reversal of neuropathic pain is associated with corticostriatal functional reorganization after nerve repair in the spared nerve injury model.

ABSTRACT: Following surgical repair after peripheral nerve injury, neuropathic pain diminishes in most patients but can persist in a small proportion of cases, the mechanism of which remains poorly understood. Based on the spared nerve injury (SNI), we developed a rat nerve repair (NR) model, where a delayed reconstruction of the SNI-injured nerves resulted in alleviating chronic pain-like behavior only in a subpopulation of rats. Multiple behavioral measures were assayed over 11-week presurgery and postsurgery periods (tactile allodynia, pain prick responses, sucrose preference, motor coordination, and cold allodynia) in SNI (n = 10), sham (n = 8), and NR (n = 12) rats. All rats also underwent resting-state functional magnetic resonance imaging under anesthesia at multiple time points postsurgery, and at 10 weeks, histology and retrograde labeling were used to calculate peripheral reinnervation. Behavioral measures indicated that at approximately 5 weeks postsurgery, the NR group separated to pain persisting (NR persisting, n = 5) and recovering (NR recovering, n = 7) groups. Counts of afferent nerves and dorsal root ganglion cells were not different between NR groups. Therefore, NR group differences could not be explained by peripheral reorganization. By contrast, large brain functional connectivity differences were observed between NR groups, where corticolimbic reorganization paralleled with pain recovery (repeated-measures analysis of variance, false discovery rate, P < 0.05), and functional connectivity between accumbens and medial frontal cortex was related both to tactile allodynia (nociception) and to sucrose preference (anhedonia) in the NR group. Our study highlights the importance of brain circuitry in the reversal of neuropathic pain as a natural pain-relieving mechanism. Further studies regarding the therapeutic potentials of these processes are warranted.

Brain signature and functional impact of centralized pain: a multidisciplinary approach to the study of chronic pelvic pain (MAPP) network study.

Chronic pain is often measured with a severity score that overlooks its spatial distribution across the body. This widespread pain is believed to be a marker of centralization, a central nervous system process that decouples pain perception from nociceptive input. Here, we investigated whether centralization is manifested at the level of the brain using data from 1079 participants in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network (MAPP) study. Participants with a clinical diagnosis of urological chronic pelvic pain syndrome (UCPPS) were compared to pain-free controls and patients with fibromyalgia, the prototypical centralized pain disorder. Participants completed questionnaires capturing pain severity, function, and a body map of pain. A subset (UCPPS N = 110; fibromyalgia N = 23; healthy control N = 49) underwent functional and structural magnetic resonance imaging. Patients with UCPPS reported pain ranging from localized (pelvic) to widespread (throughout the body). Patients with widespread UCPPS displayed increased brain gray matter volume and functional connectivity involving sensorimotor and insular cortices (P < 0.05 corrected). These changes translated across disease diagnoses as identical outcomes were present in patients with fibromyalgia but not pain-free controls. Widespread pain was also associated with reduced physical and mental function independent of pain severity. Brain pathology in patients with centralized pain is related to pain distribution throughout the body. These patients may benefit from interventions targeting the central nervous system.

Resting-state functional connectivity predicts longitudinal pain symptom change in urologic chronic pelvic pain syndrome: a MAPP network study.

Chronic pain symptoms often change over time, even in individuals who have had symptoms for years. Studying biological factors that predict trends in symptom change in chronic pain may uncover novel pathophysiological mechanisms and potential therapeutic targets. In this study, we investigated whether brain functional connectivity measures obtained from resting-state functional magnetic resonance imaging at baseline can predict longitudinal symptom change (3, 6, and 12 months after scan) in urologic chronic pelvic pain syndrome. We studied 52 individuals with urologic chronic pelvic pain syndrome (34 women, 18 men) who had baseline neuroimaging followed by symptom tracking every 2 weeks for 1 year as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network study. We found that brain functional connectivity can make a significant prediction of short-term (3 month) pain reduction with 73.1% accuracy (69.2% sensitivity and 75.0% precision). In addition, we found that the brain regions with greatest contribution to the classification were preferentially aligned with the left frontoparietal network. Resting-state functional magnetic resonance imaging measures seemed to be less informative about 6- or 12-month symptom change. Our study provides the first evidence that future trends in symptom change in patients in a state of chronic pain may be linked to functional connectivity within specific brain networks.

Brain white matter changes associated with urological chronic pelvic pain syndrome: multisite neuroimaging from a MAPP case-control study.

Clinical phenotyping of urological chronic pelvic pain syndromes (UCPPSs) in men and women have focused on end organ abnormalities to identify putative clinical subtypes. Initial evidence of abnormal brain function and structure in male pelvic pain has necessitated large-scale, multisite investigations into potential UCPPS brain biomarkers. We present the first evidence of regional white matter (axonal) abnormalities in men and women with UCPPS, compared with positive (irritable bowel syndrome, IBS) and healthy controls. Epidemiological and neuroimaging data were collected from participants with UCPPS (n = 52), IBS (n = 39), and healthy sex- and age-matched controls (n = 61). White matter microstructure, measured as fractional anisotropy (FA), was examined by diffusion tensor imaging. Group differences in regional FA positively correlated with pain severity, including segments of the right corticospinal tract and right anterior thalamic radiation. Increased corticospinal FA was specific and sensitive to UCPPS, positively correlated with pain severity, and reflected sensory (not affective) features of pain. Reduced anterior thalamic radiation FA distinguished patients with IBS from those with UCPPS and controls, suggesting greater microstructural divergence from normal tract organization. Findings confirm that regional white matter abnormalities characterize UCPPS and can distinguish between visceral diagnoses, suggesting that regional axonal microstructure is either altered with ongoing pain or predisposes its development.

Identifying brain nociceptive information transmission in patients with chronic somatic pain.

INTRODUCTION: Recent advances regarding mechanisms of chronic pain emphasize the role of corticolimbic circuitry in predicting risk for chronic pain, independently from site of injury-related parameters. These results compel revisiting the role of peripheral nociceptive signaling in chronic pain. We address this issue by examining what brain circuitry transmit information regarding the intensity of chronic pain and how this information may be related to a common co-morbidity, depression. METHODS: Resting state functional MRI was used in a large group of chronic pain patients (n=40 chronic back pain, CBP, and n=44 osteoarthritis, OA patients), and in comparison to healthy subjects (n=88). We used a graph theoretical measure, degree count, to investigate voxel-wise information sharing/transmission in the brain. Degree count, a functional connectivity based measure, identifies the number of voxels functionally connected to every given voxel. Subdividing the chronic pain cohort into discovery, replication, and also for overall group we show that only degree counts of diencephalic voxels centered in the ventral lateral thalamus reflected intensity of chronic pain, independently of depression. RESULTS: Pain intensity was reliably associated with degree count of the thalamus, which was correlated negatively with components of the default mode network and positively with the periaqueductal grey (in contrast to healthy controls). Depression scores were not reliably associated with regional degree count. CONCLUSION: Collectively the results suggest that, across two types of chronic pain, nociceptive specific information is relayed through the spinothalamic pathway to the lateral thalamus, potentiated by pro-nociceptive descending modulation, and interrupting cortical cognitive processes.

Unique Microstructural Changes in the Brain Associated with Urological Chronic Pelvic Pain Syndrome (UCPPS) Revealed by Diffusion Tensor MRI, Super-Resolution Track Density Imaging, and Statistical Parameter Mapping: A MAPP Network Neuroimaging Study.

Studies have suggested chronic pain syndromes are associated with neural reorganization in specific regions associated with perception, processing, and integration of pain. Urological chronic pelvic pain syndrome (UCPPS) represents a collection of pain syndromes characterized by pelvic pain, namely Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) and Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS), that are both poorly understood in their pathophysiology, and treated ineffectively. We hypothesized patients with UCPPS may have microstructural differences in the brain compared with healthy control subjects (HCs), as well as patients with irritable bowel syndrome (IBS), a common gastrointestinal pain disorder. In the current study we performed population-based voxel-wise DTI and super-resolution track density imaging (TDI) in a large, two-center sample of phenotyped patients from the multicenter cohort with UCPPS (N = 45), IBS (N = 39), and HCs (N = 56) as part of the MAPP Research Network. Compared with HCs, UCPPS patients had lower fractional anisotropy (FA), lower generalized anisotropy (GA), lower track density, and higher mean diffusivity (MD) in brain regions commonly associated with perception and integration of pain information. Results also showed significant differences in specific anatomical regions in UCPPS patients when compared with IBS patients, consistent with microstructural alterations specific to UCPPS. While IBS patients showed clear sex related differences in FA, MD, GA, and track density consistent with previous reports, few such differences were observed in UCPPS patients. Heat maps illustrating the correlation between specific regions of interest and various pain and urinary symptom scores showed clustering of significant associations along the cortico-basal ganglia-thalamic-cortical loop associated with pain integration, modulation, and perception. Together, results suggest patients with UCPPS have extensive microstructural differences within the brain, many specific to syndrome UCPPS versus IBS, that appear to be localized to regions associated with perception and integration of sensory information and pain modulation, and seem to be a consequence of longstanding pain.

Altered resting state neuromotor connectivity in men with chronic prostatitis/chronic pelvic pain syndrome: A MAPP: Research Network Neuroimaging Study.

Brain network activity associated with altered motor control in individuals with chronic pain is not well understood. Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a debilitating condition in which previous studies have revealed altered resting pelvic floor muscle activity in men with CP/CPPS compared to healthy controls. We hypothesized that the brain networks controlling pelvic floor muscles would also show altered resting state function in men with CP/CPPS. Here we describe the results of the first test of this hypothesis focusing on the motor cortical regions, termed pelvic-motor, that can directly activate pelvic floor muscles. A group of men with CP/CPPS (N = 28), as well as group of age-matched healthy male controls (N = 27), had resting state functional magnetic resonance imaging scans as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network study. Brain maps of the functional connectivity of pelvic-motor were compared between groups. A significant group difference was observed in the functional connectivity between pelvic-motor and the right posterior insula. The effect size of this group difference was among the largest effect sizes in functional connectivity between all pairs of 165 anatomically-defined subregions of the brain. Interestingly, many of the atlas region pairs with large effect sizes also involved other subregions of the insular cortices. We conclude that functional connectivity between motor cortex and the posterior insula may be among the most important markers of altered brain function in men with CP/CPPS, and may represent changes in the integration of viscerosensory and motor processing.

The posterior medial cortex in urologic chronic pelvic pain syndrome: detachment from default mode network-a resting-state study from the MAPP Research Network.

Altered resting-state (RS) brain activity, as a measure of functional connectivity (FC), is commonly observed in chronic pain. Identifying a reliable signature pattern of altered RS activity for chronic pain could provide strong mechanistic insights and serve as a highly beneficial neuroimaging-based diagnostic tool. We collected and analyzed RS functional magnetic resonance imaging data from female patients with urologic chronic pelvic pain syndrome (N = 45) and matched healthy participants (N = 45) as part of an NIDDK-funded multicenter project (www.mappnetwork.org). Using dual regression and seed-based analyses, we observed significantly decreased FC of the default mode network to 2 regions in the posterior medial cortex (PMC): the posterior cingulate cortex (PCC) and the left precuneus (threshold-free cluster enhancement, family-wise error corrected P < 0.05). Further investigation revealed that patients demonstrated increased FC between the PCC and several brain regions implicated in pain, sensory, motor, and emotion regulation processes (eg, insular cortex, dorsolateral prefrontal cortex, thalamus, globus pallidus, putamen, amygdala, hippocampus). The left precuneus demonstrated decreased FC to several regions of pain processing, reward, and higher executive functioning within the prefrontal (orbitofrontal, anterior cingulate, ventromedial prefrontal) and parietal cortices (angular gyrus, superior and inferior parietal lobules). The altered PMC connectivity was associated with several phenotype measures, including pain and urologic symptom intensity, depression, anxiety, quality of relationships, and self-esteem levels in patients. Collectively, these findings indicate that in patients with urologic chronic pelvic pain syndrome, regions of the PMC are detached from the default mode network, whereas neurological processes of self-referential thought and introspection may be joined to pain and emotion regulatory processes.

Brain White Matter Abnormalities in Female Interstitial Cystitis/Bladder Pain Syndrome: A MAPP Network Neuroimaging Study.

PURPOSE: Several chronic pain conditions may be distinguished by condition specific brain anatomical and functional abnormalities on imaging, which are suggestive of underlying disease processes. We present what is to our knowledge the first characterization of interstitial cystitis/bladder pain syndrome associated white matter (axonal) abnormalities based on multicenter neuroimaging from the MAPP Research Network. MATERIALS AND METHODS: We assessed 34 women with interstitial cystitis/bladder pain syndrome and 32 healthy controls using questionnaires on pain, mood and daily function. White matter microstructure was evaluated by diffusion tensor imaging to model directional water flow along axons or fractional anisotropy. Regions correlating with clinical parameters were further examined for gender and syndrome dependence. RESULTS: Women with interstitial cystitis/bladder pain syndrome showed numerous white matter abnormalities that correlated with pain severity, urinary symptoms and impaired quality of life. Interstitial cystitis/bladder pain syndrome was characterized by decreased fractional anisotropy in aspects of the right anterior thalamic radiation, the left forceps major and the right longitudinal fasciculus. Increased fractional anisotropy was detected in the right superior and bilateral inferior longitudinal fasciculi. CONCLUSIONS: To our knowledge we report the first characterization of brain white matter abnormalities in women with interstitial cystitis/bladder pain syndrome. Regional decreases and increases in white matter integrity across multiple axonal tracts were associated with symptom severity. Given that white matter abnormalities closely correlated with hallmark symptoms of interstitial cystitis/bladder pain syndrome, including bladder pain and urinary symptoms, brain anatomical alterations suggest that there are neuropathological contributions to chronic urological pelvic pain.

Increased brain gray matter in the primary somatosensory cortex is associated with increased pain and mood disturbance in patients with interstitial cystitis/painful bladder syndrome.

PURPOSE: Interstitial cystitis is a highly prevalent pain condition estimated to affect 3% to 6% of women in the United States. Emerging data suggest there are central neurobiological components to the etiology of this disease. We report the first brain structural imaging findings from the MAPP network with data on more than 300 participants. MATERIALS AND METHODS: We used voxel based morphometry to determine whether human patients with chronic interstitial cystitis display changes in brain morphology compared to healthy controls. A total of 33 female patients with interstitial cystitis without comorbidities and 33 age and gender matched controls taken from the larger sample underwent structural magnetic resonance imaging at 5 MAPP sites across the United States. RESULTS: Compared to controls, females with interstitial cystitis displayed significant increased gray matter volume in several regions of the brain including the right primary somatosensory cortex, the superior parietal lobule bilaterally and the right supplementary motor area. Gray matter volume in the right primary somatosensory cortex was associated with greater pain, mood (anxiety) and urological symptoms. We explored these correlations in a linear regression model, and found independent effects of these 3 measures on primary somatosensory cortex gray matter volume, namely clinical pain (McGill pain sensory total), a measure of urgency and anxiety (HADS). CONCLUSIONS: These data support the notion that changes in somatosensory gray matter may have an important role in pain sensitivity as well as affective and sensory aspects of interstitial cystitis. Further studies are needed to confirm the generalizability of these findings to other pain conditions.

Preliminary structural MRI based brain classification of chronic pelvic pain: A MAPP network study.

Neuroimaging studies have shown that changes in brain morphology often accompany chronic pain conditions. However, brain biomarkers that are sensitive and specific to chronic pelvic pain (CPP) have not yet been adequately identified. Using data from the Trans-MAPP Research Network, we examined the changes in brain morphology associated with CPP. We used a multivariate pattern classification approach to detect these changes and to identify patterns that could be used to distinguish participants with CPP from age-matched healthy controls. In particular, we used a linear support vector machine (SVM) algorithm to differentiate gray matter images from the 2 groups. Regions of positive SVM weight included several regions within the primary somatosensory cortex, pre-supplementary motor area, hippocampus, and amygdala were identified as important drivers of the classification with 73% overall accuracy. Thus, we have identified a preliminary classifier based on brain structure that is able to predict the presence of CPP with a good degree of predictive power. Our regional findings suggest that in individuals with CPP, greater gray matter density may be found in the identified distributed brain regions, which are consistent with some previous investigations in visceral pain syndromes. Future studies are needed to improve upon our identified preliminary classifier with integration of additional variables and to assess whether the observed differences in brain structure are unique to CPP or generalizable to other chronic pain conditions.

Pain reduces sexual motivation in female but not male mice.

Chronic pain is often associated with sexual dysfunction, suggesting that pain can reduce libido. We find that inflammatory pain reduces sexual motivation, measured via mounting behavior and/or proximity in a paced mating paradigm, in female but not male laboratory mice. Pain was produced by injection of inflammogens zymosan A (0.5 mg/ml) or λ-carrageenan (2%) into genital or nongenital (hind paw, tail, cheek) regions. Sexual behavior was significantly reduced in female mice experiencing pain (in all combinations); male mice similarly treated displayed unimpeded sexual motivation. Pain-induced reductions in female sexual behavior were observed in the absence of sex differences in pain-related behavior, and could be rescued by the analgesic, pregabalin, and the libido-enhancing drugs, apomorphine and melanotan-II. These findings suggest that the well known context sensitivity of the human female libido can be explained by evolutionary rather than sociocultural factors, as female mice can be similarly affected.

Alterations in resting state oscillations and connectivity in sensory and motor networks in women with interstitial cystitis/painful bladder syndrome.

PURPOSE: The pathophysiology of interstitial cystitis/painful bladder syndrome remains incompletely understood but is thought to involve central disturbance in the processing of pain and viscerosensory signals. We identified differences in brain activity and connectivity between female patients with interstitial cystitis/painful bladder syndrome and healthy controls to advance clinical phenotyping and treatment efforts for interstitial cystitis/painful bladder syndrome. MATERIALS AND METHODS: We examined oscillation dynamics of intrinsic brain activity in a large sample of well phenotyped female patients with interstitial cystitis/painful bladder syndrome and female healthy controls. Data were collected during 10-minute resting functional magnetic resonance imaging as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network project. The blood oxygen level dependent signal was transformed to the frequency domain. Relative power was calculated for multiple frequency bands. RESULTS: Results demonstrated altered frequency distributions in viscerosensory (post insula), somatosensory (postcentral gyrus) and motor regions (anterior paracentral lobule, and medial and ventral supplementary motor areas) in patients with interstitial cystitis/painful bladder syndrome. Also, the anterior paracentral lobule, and medial and ventral supplementary motor areas showed increased functional connectivity to the midbrain (red nucleus) and cerebellum. This increased functional connectivity was greatest in patients who reported pain during bladder filling. CONCLUSIONS: Findings suggest that women with interstitial cystitis/painful bladder syndrome have a sensorimotor component to the pathological condition involving an alteration in intrinsic oscillations and connectivity in a cortico-cerebellar network previously associated with bladder function.

Predicting transition to chronic pain.

PURPOSE OF REVIEW: Most individuals who develop pain following an inciting event will return to a healthy state as the injury heals. However, a small percentage continue to suffer, that is, transition to chronic pain. Chronic pain may persist for years and is accompanied by cognitive abnormalities, as well as diminished quality of life. In animals, persistent pain is characterized by peripheral and spinal cord reorganization, and recent evidence in humans also indicates cortical reorganization. Yet, despite more than 30 years of research, there is little agreement on the neural mechanisms that mediate the transition from acute to chronic pain. RECENT FINDINGS: In a longitudinal brain-imaging study, individuals who developed an intense back pain episode were followed over a 1-year period, during which pain and brain parameters were collected repeatedly. A smaller number of healthy individuals and chronic back pain patients were also studied concomitantly, as positive and negative controls. At the time of entry into the study, strength of synchrony between the medial prefrontal cortex and nucleus accumbens (i.e. functional connectivity) was predictive (>80% accuracy) of individuals who subsequently transition to chronicity 1 year later. SUMMARY: Properties of the brain's emotional learning circuitry predict the transition to chronic pain. The involvement of this circuitry in pain remains mostly unexplored. Future human and animal model studies are necessary to unravel underlying mechanisms driving pain chronicity, with the potential of advancing novel therapeutics for preventing pain chronification.

Psychophysical properties of female genital sensation.

Provoked vestibulodynia (PVD) is characterized by the presence of vulvar touch and pain hypersensitivity. Pain with vaginal distension, which motivates treatment seeking and perpetuates distress, is frequently reported with PVD. However, the concordance between the perception of vulvar and vaginal sensation (ie, somatic and visceral genital sensations, respectively) remains unstudied in healthy women, as well as in clinical populations such as PVD. To evaluate the static and dynamic (time-varying) properties of somatic and visceral genital sensation, women with PVD (n=14) and age- and contraceptive-matched healthy controls (n=10) rated varying degrees of nonpainful and painful genital stimulation. Somatic (vulvar) mechanical sensitivity to nonpainul and painful degrees of force were compared to visceral (vaginal) sensitivity to nonpainful and painful distension volumes. Results indicated that healthy women showed substantial individual variation in and high discrimination of vulvar and vaginal sensation. In contrast, PVD was associated with vulvar allodynia and hyperalgesia, as well as vaginal allodynia. Modeling of dynamic perception revealed novel properties of abnormal PVD genital sensation, including temporal delays in vulvar touch perception and reduced perceptual thresholds for vaginal distension. The temporal properties and magnitude of PVD distension pain were indistinguishable from vaginal fullness in healthy controls. These results constitute the first empirical comparison of somatic and visceral genital sensation in healthy women. Findings provide novel insights into the sensory abnormalities that characterize PVD, including an experimental demonstration of visceral allodynia. This investigation challenges the prevailing diagnostic assessment of PVD and reconceptualizes PVD as a chronic somatic and visceral pain condition.

A dynamic network perspective of chronic pain.

We briefly summarize recent advances regarding brain functional representation of chronic pain, reorganization of resting state brain activity, and of brain anatomy with chronic pain. Based on these observations and recent theoretical advances regarding network architecture properties, we develop a general concept of the dynamic interplay between anatomy and function as the brain progresses into persistent pain, and outline the role of mesolimbic learning mechanisms that are likely involved in maintenance of chronic pain.

Repeated vulvovaginal fungal infections cause persistent pain in a mouse model of vulvodynia.

Provoked vestibulodynia, the most common form of vulvodynia (unexplained pain of the vulva), is a prevalent, idiopathic pain disorder associated with a history of recurrent candidiasis (yeast infections). It is characterized by vulvar allodynia (painful hypersensitivity to touch) and hyperinnervation. We tested whether repeated, localized exposure of the vulva to a common fungal pathogen can lead to the development of chronic pain. A subset of female mice subjected to recurrent Candida albicans infection developed mechanical allodynia localized to the vulva. The mice with allodynia also exhibited hyperinnervation with peptidergic nociceptor and sympathetic fibers (as indicated by increased protein gene product 9.5, calcitonin gene-related peptide, and vesicular monoamine transporter 2 immunoreactivity in the vaginal epithelium). Long-lasting behavioral allodynia in a subset of mice was also observed after a single, extended Candida infection, as well as after repeated vulvar (but not hind paw) inflammation induced with zymosan, a mixture of fungal antigens. The hypersensitivity and hyperinnervation were both present at least 3 weeks after the resolution of infection and inflammation. Our data show that infection can cause persistent pain long after its resolution and that recurrent yeast infection replicates important features of human provoked vulvodynia in the mouse.

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

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.

The relation between sexual behavior and religiosity subtypes: a test of the secularization hypothesis.

Previous literature on religion and sexual behavior has focused on narrow definitions of religiosity, including religious affiliation, religious participation, or forms of religiousness (e.g., intrinsic religiosity). Trends toward more permissive premarital sexual activity in the North American Christian-Judeo religion support the secularization hypothesis of religion, which posits an increasing gap between religious doctrine and behavior. However, the recent rise of fundamentalist and new age religious movements calls for a reexamination of the current link between religion and sexual behavior. The use of dual definitions of religiosity, including religious affiliation and dimensional subtypes, may further characterize this link. The present cross-sectional study evaluated patterns of sexual behavior in a young adult sample (N = 1302, M age = 18.77 years) in the context of the secularization hypothesis using religious affiliation and a liberal-conservative continuum of religious subtypes: paranormal belief, spirituality, intrinsic religiosity, and fundamentalism. Results indicated few affiliation differences in sexual behavior in men or women. Sexual behaviors were statistically predicted by spirituality, fundamentalism, and paranormal belief, and the endorsement of fundamentalism in particular was correlated with lower levels of female sexual behavior. The secularization hypothesis was supported by consistent levels of sexual activity across affiliations and is contradicted by the differential impact of religiosity subtypes on sexual behavior. Findings suggested that the use of religious subtypes to evaluate religious differences, rather than solely affiliation, may yield useful insights into the link between religion and sexual behavior.