Cortical Mechanisms of Visual Hypersensitivity in Women at Risk for Chronic Pelvic Pain.
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ABSTRACT:
SUBMITTER: Kmiecik MJ
PROVIDER: S-EPMC7836135 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is the most common urologic morbidity in men younger than 50 years and is characterized by a diverse range of pain and inflammatory symptoms, both in type and severity, that involve the region of the pelvis, perineum, scrotum, rectum, testes, penis, and lower back. In most patients, pain is accompanied by inflammation in the absence of an invading infectious agent. Since CP/CPPS etiology is still not well established, available therapeutic options for patients are far from satisfactory for either physicians or patients. During the past two decades, chronic inflammation has been deeply explored as the cause of CP/CPPS. In this review article, we summarize the current knowledge regarding immunological mechanisms underlying chronic pelvic pain and prostate inflammation in CP/CPPS. Cumulative evidence obtained from both human disease and animal models indicate that several factors may trigger chronic inflammation in the form of autoimmunity against prostate, fostering chronic prostate recruitment of Th1 cells, and different other leukocytes, including mast cells, which might be the main actors in the consequent development of chronic pelvic pain. Thus, the local inflammatory milieu and the secretion of inflammatory mediators may induce neural sensitization leading to chronic pelvic pain development. Although scientific advances are encouraging, additional studies are urgently needed to establish the relationship between prostatitis development, mast cell recruitment to the prostate, and the precise mechanisms by which they would induce pelvic pain.
| S-EPMC5535188 | biostudies-other
Project description:PurposeWe determined whether abnormal autonomic nervous system innervation of the bladder underlies IC (interstitial cystitis)/BPS (bladder pain syndrome) differently than other chronic pelvic pain.Materials and methodsIn this institutional review board approved protocol 39 healthy controls and 134 subjects were enrolled, including 36 with IC/BPS, 14 with myofascial pelvic pain and 42 with IC/BPS plus myofascial pelvic pain. Three subjects were excluded from study. Autonomic nervous system evaluations included deep breathing, the Valsalva maneuver, and the tilt table and sudomotor tests. The latter evaluates autonomic neuropathy. A modified validated composite autonomic laboratory score was applied.ResultsMedian age in the IC/BPS group was 47.5 years (range 21 to 78), greater than in healthy controls (34 years, range 20 to 75, p = 0.006), the myofascial pelvic pain group (33 years, range 22 to 56, p = 0.004) and the IC/BPS plus myofascial pelvic pain group (38 years, range 18 to 64, p = 0.03). Body mass index did not significantly differ but the myofascial pelvic pain and IC/BPS plus myofascial pelvic pain groups had a higher body mass index than healthy controls (p = 0.05 and 0.03, respectively). Cardiovascular and adrenergic indexes did not differ. The tilt table test showed more orthostatic intolerance in all chronic pelvic pain groups. Tilt table test diagnoses (orthostatic hypotension, postural tachycardia syndrome and reflex syncope) were rare. Baseline heart rate was higher in all chronic pelvic pain groups (p = 0.004). Compared to healthy controls all myofascial pelvic pain groups showed significantly more clear-cut autonomic neuropathy, defined as a sweat score of 3 or greater (vs IC/BPS plus myofascial pelvic pain p = 0.007 and vs myofascial pelvic pain p = 0.03).ConclusionsSome chronic pelvic pain types show autonomic neuropathy and some show vagal withdrawal. In all types orthostatic intolerance likely reflects central sensitization and perhaps catastrophizing. Some of these findings suggest novel therapeutic targets.
| S-EPMC4969223 | biostudies-literature
Project description:Exploring the relationship between nociplastic pain and the severity and impact of pelvic pain symptoms could lend insight into the heterogeneous symptom presentation and treatment response that complicates management of chronic pelvic pain. In this prospective cross-sectional study, we sought to evaluate relationships between degree of nociplastic pain, measured by the Fibromyalgia (FM) Survey Score, and multiple aspects of the chronic pelvic pain (CPP) experience, including severity, frequency, tenderness during pelvic myofascial exam, interference with daily life, and high-impact pain. The study included 303 women who presented to a tertiary referral clinic for chronic pelvic pain and endometriosis. Multiple measures of pelvic pain, including pain severity, frequency, interference, pelvic myofascial pain, and high-impact pain were examined in General Linear Models with FM Survey Score as the primary predictor of interest in models controlling for endometriosis, surgical history, use of opioids, body mass index, and patient age. Higher level of nociplastic pain was associated with greater pelvic pain severity, frequency, interference, and pelvic myofascial pain (all P < .05). For all models, degree of nociplastic pain was more strongly associated with pain outcomes than the presence of endometriosis, and use of opioids was the only stronger predictor of worse pain outcomes. The likelihood of high impact pain increased 7% for each additional point on the FM Survey Score. Degree of nociplastic pain was robustly associated with severity, frequency, and impact of pelvic pain, and was independent of the presence of endometriosis, history of surgical procedures for pelvic pain, age, and BMI. Trial registration: not applicable PERSPECTIVE: This article evaluates the impact of nociplastic pain on symptoms and functional status in chronic pelvic pain. These findings raise the possibility that a simple screening tool for nociplastic pain might provide clinically actionable information without the need for deep neurobiological phenotyping and may inform development of personalized management strategies.
| S-EPMC10511662 | biostudies-literature
Project description:ObjectiveTo examine the prevalence of migraine in women with chronic pelvic pain with and without endometriosis.DesignProspective study of headache, pelvic pain, and quality of life before laparoscopic surgery for pelvic pain. Endometriosis was diagnosed pathologically. Headaches were classified as migraine or non-migraine using International Headache Society criteria.SettingClinical research hospital.Patient(s)108 women in a clinical trial for chronic pelvic pain (NCT00001848).Intervention(s)Laparoscopy to diagnose endometriosis, assessment by neurologist to assess headaches.Main outcome measure(s)Prevalence of migraine and other headaches in women with chronic pelvic pain with or without endometriosis. Headache frequency, severity and relationship to pelvic pain and endometriosis.Result(s)Lifetime prevalence of definite or possible migraine was 67% of women with chronic pelvic pain. An additional 8% met criteria for possible migraine. Migraine was no more likely in women with endometriosis than those without. Women with the most severe headaches had a lower quality of life compared with those with pelvic pain alone.Conclusion(s)Migraine headache is common in women with chronic pelvic pain, regardless of endometriosis, and contributes to disability in those with both conditions. The strong association suggests a common pathophysiology.
| S-EPMC3415219 | biostudies-literature
Project description:PurposeInterstitial cystitis/bladder pain syndrome and myofascial pelvic pain are frequently comorbid chronic pelvic pain disorders. Differences in bladder function between interstitial cystitis/bladder pain syndrome and myofascial pelvic pain suggest that efferent autonomic function may differentiate these syndromes. Heart rate variability, defined as the difference in duration of successive heartbeats, serves as an index of autonomic function by measuring its ability to modify heart rate in response to neurophysiological changes. High frequency heart rate variability was used as a reflection of more rapid vagally mediated (parasympathetic) changes. Low frequency heart rate variability signified slower fluctuations related to the baroreflex and sympathetic outflow.Materials and methodsHeart rate variability was derived by autoregressive frequency analysis of the continuous electrocardiogram recording of heart rate with the subject supine for 10 minutes, tilted 70 degrees with the head up for 30 minutes and supine again for 10 minutes. This institutional review board approved study included 105 female subjects, including 32 who were healthy, and 26 with interstitial cystitis/bladder pain syndrome, 12 with myofascial pelvic pain and 35 with interstitial cystitis/bladder pain syndrome plus myofascial pelvic pain.ResultsIn all positions healthy controls had higher high frequency heart rate variability than women with interstitial cystitis/bladder pain syndrome and interstitial cystitis/bladder pain syndrome plus myofascial pelvic pain. Subjects with myofascial pelvic pain were similar to controls with greater high frequency heart rate variability at baseline (supine 1) and in upright positions than subjects with interstitial cystitis/bladder pain syndrome. Differences in low frequency heart rate variability were less evident while low-to-high frequency ratio differences appeared to be driven by the high frequency heart rate variability component.ConclusionsSubjects with interstitial cystitis/bladder pain syndrome had diminished vagal activity and a shift toward sympathetic nervous system dominance. Overall these data support the hypothesis that changes in autonomic function occur in interstitial cystitis/bladder pain syndrome but not in myofascial pelvic pain. These changes may result from interstitial cystitis/bladder pain syndrome or contribute to its pathophysiology through abnormal self-regulatory function.
| S-EPMC8753597 | biostudies-literature
Project description:ObjectivePelvic floor pain, abdominal wall pain, and central nervous system pain amplification can be contributing factors in chronic pelvic pain (CPP), however; limited research has investigated the association of pelvic floor, abdominal, and uterine tenderness with central nervous system pain amplification. We assessed whether pressure pain thresholds on the non-dominant thumbnail, a marker of central nervous system pain amplification, were associated with pelvic floor, abdominal, and uterine tenderness among women with endometriosis or CPP.Study designWe conducted a cross-sectional study among 88 females with endometriosis and/or CPP. Abdominal (6 locations), pelvic floor (6 locations) and uterine (1 location) tenderness were assessed via a standardized physical exam. Participants reported their pain levels (0-10 scale) with application of 2 kg of pressure at each area, with a pain rating of ≥4 on the 0-10 scale considered moderate to severe pain. Pain sensitivity was measured on the non-dominant thumbnail by applying discrete pressure stimuli using a previously validated protocol.ResultsOverall, 50% (44/88), 42% (37/88), and 58% (51/88) of participants reported high pelvic floor, abdominal, and uterine tenderness, respectively. Pressure intensities needed to elicit 'faint' and 'mild' pain were lower for participants with high vs. low pelvic floor tenderness (median intensity for 'faint' pain = 0.50 kgf/cm2(min-max:0.25-3.25) vs. 1.06(0.25-3.00), p-value = 0.006; median intensity for 'mild' pain = 2.00(0.63-4.88) vs. 2.63(0.75-6.00), p-value = 0.03). No association was observed between pressure pain sensitivity and abdominal or uterine tenderness (p > 0.11). Participants with endometriosis without pain were less likely to have high pelvic floor (22.2%), abdominal (11.1%), and uterine (25.9%) tenderness compared to participants with endometriosis with pain (63.0%, 50%, 65.2%, respectively) and participants with chronic pelvic pain (60%, 73.3%, 93.3%, respectively).ConclusionsThese results suggest that high pelvic floor tenderness among women with endometriosis/CPP may be a marker of heightened pain sensitivity suggestive of central nervous system pain amplification and may impact treatment response. Future research should examine whether this clinical phenotype predicts response to medical and behavioral treatments (e.g, anti-convulsants, behavioral therapy, Physical Therapy).
| S-EPMC8449805 | biostudies-literature
Project description:The study investigated the cellular and molecular mechanisms in the peripheral nervous system (PNS) underlying the symptoms of urologic chronic pelvic pain syndrome (UCPPS) in mice. This work also aimed to test the feasibility of reversing peripheral sensitization in vivo in alleviating UCPPS symptoms. Intravesical instillation of vascular endothelial growth factor A (VEGFA) was used to induce UCPPS-like symptoms in mice. Spontaneous voiding spot assays and manual Von Frey tests were used to evaluate the severity of lower urinary tract symptoms (LUTS) and visceral hypersensitivity in VEGFA-instilled mice. Bladder smooth muscle strip contractility recordings (BSMSC) were used to identify the potential changes in myogenic and neurogenic detrusor muscle contractility at the tissue-level. Quantitative real-time PCR (qPCR) and fluorescent immunohistochemistry were performed to compare the expression levels of VEGF receptors and nociceptors in lumbosacral dorsal root ganglia (DRG) between VEGFA-instilled mice and saline-instilled controls. To manipulate primary afferent activity, Gi-coupled Designer Receptors Exclusively Activated by Designer Drugs (Gi-DREADD) were expressed in lumbosacral DRG neurons of TRPV1-Cre-ZGreen mice via targeted adeno-associated viral vector (AAVs) injections. A small molecule agonist of Gi-DREADD, clozapine-N-oxide (CNO), was injected into the peritoneum (i. p.) in awake animals to silence TRPV1 expressing sensory neurons in vivo during physiological and behavioral recordings of bladder function. Intravesical instillation of VEGFA in the urinary bladders increased visceral mechanical sensitivity and enhanced RTX-sensitive detrusor contractility. Sex differences were identified in the baseline detrusor contractility responses and VEGF-induced visceral hypersensitivity. VEGFA instillations in the urinary bladder led to significant increases in the mRNA and protein expression of transient receptor potential cation channel subfamily A member 1 (TRPA1) in lumbosacral DRG, whereas the expression levels of transient receptor potential cation channel subfamily V member 1 (TRPV1) and VEGF receptors (VEGFR1 and VEGFR2) remained unchanged when compared to saline-instilled animals. Importantly, the VEGFA-induced visceral hypersensitivity was reversed by Gi-DREADD-mediated neuronal silencing in lumbosacral sensory neurons. Activation of bladder VEGF signaling causes sensory neural plasticity and visceral hypersensitivity in mice, confirming its role of an UCPPS biomarker as identified by the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) research studies. Pharmacogenetic inhibition of lumbosacral sensory neurons in vivo completely reversed VEGFA-induced pelvic hypersensitivity in mice, suggesting the strong therapeutic potential for decreasing primary afferent activity in the treatment of pain severity in UCPPS patients.
| S-EPMC8789164 | biostudies-literature
Project description:OBJECTIVE:To examine the feasibility of implementing a standardized, clinically relevant genitourinary examination for both men and women, and to identify physical examination findings characteristic of urologic chronic pelvic pain syndrome (UCPPS). MATERIALS AND METHODS:This study analyzed 2 samples: men and women with UCPPS who participated in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network Epidemiology and Phenotyping (EP) Study, and age-matched controls who were either positive for chronic fatigue syndrome or healthy (pain-free). We compared physical examination findings in both positive and healthy controls with UCPPS cases: findings from both the EP examinations and from an extended genitourinary examination. RESULTS:EP and extended examinations were performed on 143 participants: 62 UCPPS cases (30 women, 32 men), 42 positive controls (15 women, 27 men), and 39 healthy controls (22 women, 17 men). EP examinations showed that pelvic floor tenderness was more prevalent in cases (55.0%) than in positive (14.6%) or healthy controls (10.5%). Extended examinations revealed specific areas of tenderness in the pelvic floor musculature. Cases were also more likely than healthy controls to report tenderness in multiple areas, including suprapubic, symphysis pubis, and posterior superior iliac spine, and on bimanual examination. No comparative findings were specific to biological sex, and no evidence of pudendal neuropathy was observed on extended examination of cases or controls. CONCLUSION:The extended genitourinary examination is an easily administered addition to the assessment of men and women during evaluation for UCPPS. Physical findings may help to better categorize patients with UCPPS into clinically relevant subgroups for optimal treatment.
| S-EPMC6237096 | biostudies-literature
Project description:To determine the feasibility of a detailed pain sensitivity assessment using body-wide musculoskeletal tender points (TPs) in women with different types of chronic pelvic pain (CPP) and compare phenotypic differences.Seventy women with CPP and 35 pain-free women underwent musculoskeletal evaluation of TPs in the pelvic floor, abdomen, groin, inner thigh, and all 18 fibromyalgia TPs. Patients scored elicited pain on a numeric rating scale. TP pain scores were used for intergroup comparison and intragroup correlation.Women with CPP were grouped as having either bladder pain syndrome (BPS, n=24) or myofascial pelvic pain (MPP, n=11) singularly or both concomitantly (BPS+MPP, n=35). TP pain scores for all evaluations were higher in women with CPP compared with healthy women (P<0.001). Women with BPS+MPP had elevated TP pain for each evaluation compared with women with BPS alone. Pelvic floor and fibromyalgia TP scores correlated strongly in the MPP group, moderately in the BPS+MPP group, and weakly in the BPS alone group. Although some moderate and strong correlations between different body locations were present in all 3 groups, only the BPS+MPP group showed moderate to strong correlations between all body TPs.Detailed musculoskeletal evaluation of women with CPP is feasible and well tolerated. Careful phenotyping differentiated BPS, MPP, and BPS+MPP groups. Attending to the differences between these groups clinically may lead to more effective treatment strategies and improved outcomes for patients with CPP.
| S-EPMC4840091 | biostudies-literature
Project description:BackgroundChronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a disease with diverse clinical manifestations, such as pelvic pain or perineal pain. Although recent studies found several risk factors related to the pain severity of CP/CPPS patients, results were inconsistent. Here, we aimed to identify novel risk factors that are closely related to the severity of pain in patients with CP/CPPS.MethodsWe retrospectively collected the clinical records from patients with CP/CPPS from March 2019 to October 2019. The questionnaire was used to obtain related parameters, such as demographics, lifestyle, medical history, etc. To identify potential risk factors related to pain severity, we used the methods of univariate and multivariate logistic regression analyses. Further, to confirm the relationship between these confirmed risk factors and CP/CPPS, we randomly divided CP/CPPS patients into the training and the validation cohorts with a ratio of 7:3. According to the co-efficient result of each risk factor calculated by multivariate logistic regression analysis, a predicting model of pain severity was established. The receiver operating characteristic curve (ROC), discrimination plot, calibration plot, and decision curve analyses (DCA) were used to evaluate the clinical usage of the current model in both the training and validation cohorts.ResultsA total of 272 eligible patients were enrolled. The univariate and multivariate logistic regression analysis found that age [odds ratio (OR): 2.828, 95% confidence intervals (CI): 1.239-6.648, P = 0.004], holding back urine (OR: 2.413, 95% CI: 1.213-4.915, P = 0.005), anxiety or irritability (OR: 3.511, 95% CI: 2.034-6.186, P < 0.001), contraception (OR: 2.136, 95% CI:1.161-3.014, P = 0.029), and smoking status (OR: 1.453, 95% CI: 1.313-5.127, P = 0.013) were the risk factors of pain severity. We then established a nomogram model, to test whether these factors could be used to predict the pain severity of CP/CPPS patients in turn. Finally, ROC, DCA, and calibration analyses proved the significance and stability of this nomogram, further confirmed that these factors were closely related to the pain severity of CP/CPPS patients.ConclusionsWe identify age, holding back urine, anxiety or irritability, contraception, and smoking are risk factors closely related to the pain severity in patients with CP/CPPS. Our results provide novel inspirations for clinicians to design the personalized treatment plan for individual CP/CPPS patient who has suffered different encounters.
| S-EPMC7542966 | biostudies-literature