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Multimodal hypersensitivity derived from quantitative sensory testing predicts pelvic pain outcome: an observational cohort study.

ABSTRACT:

Abstract

Multimodal hypersensitivity (MMH)-greater sensitivity across multiple sensory modalities (eg, light, sound, temperature, pressure)-is associated with the development of chronic pain. However, previous MMH studies are restricted given their reliance on self-reported questionnaires, narrow use of multimodal sensory testing, or limited follow-up. We conducted multimodal sensory testing on an observational cohort of 200 reproductive-aged women, including those at elevated risk for chronic pelvic pain conditions and pain-free controls. Multimodal sensory testing included visual, auditory, and bodily pressure, pelvic pressure, thermal, and bladder pain testing. Self-reported pelvic pain was examined over 4 years. A principal component analysis of sensory testing measures resulted in 3 orthogonal factors that explained 43% of the variance: MMH, pressure pain stimulus response, and bladder hypersensitivity. The MMH and bladder hypersensitivity factors correlated with baseline self-reported menstrual pain, genitourinary symptoms, depression, anxiety, and health. Over time, MMH increasingly predicted pelvic pain and was the only component to predict outcome 4 years later, even when adjusted for baseline pelvic pain. Multimodal hypersensitivity was a better predictor of pelvic pain outcome than a questionnaire-based assessment of generalized sensory sensitivity. These results suggest that MMHs overarching neural mechanisms convey more substantial long-term risk for pelvic pain than variation in individual sensory modalities. Further research on the modifiability of MMH could inform future treatment developments in chronic pain.

SUBMITTER: Kmiecik MJ

PROVIDER: S-EPMC10440257 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Multimodal hypersensitivity derived from quantitative sensory testing predicts pelvic pain outcome: an observational cohort study.

Kmiecik Matthew J MJ Tu Frank F FF Clauw Daniel J DJ Hellman Kevin M KM

Pain 20230427 9

<h4>Abstract</h4>Multimodal hypersensitivity (MMH)-greater sensitivity across multiple sensory modalities (eg, light, sound, temperature, pressure)-is associated with the development of chronic pain. However, previous MMH studies are restricted given their reliance on self-reported questionnaires, narrow use of multimodal sensory testing, or limited follow-up. We conducted multimodal sensory testing on an observational cohort of 200 reproductive-aged women, including those at elevated risk for c ...[more]

PMID: 37226937

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Project description:BackgroundJuvenile Idiopathic Arthritis (JIA) is the most common cause of non-infectious joint inflammation in children. Synovial inflammation results in pain, swelling and stiffness. Animal and adult human studies indicate that localized joint-associated inflammation may produce generalized changes in pain sensitivity. The aim was to characterize pain sensitivity in children with JIA to mechanical and thermal stimulus modalities using quantitative sensory testing (QST) at an affected inflamed joint, and compare to children in clinical remission. Generalized hypersensitivity was evaluated by comparing QST measures at the thenar eminence between JIA and healthy control children.Methods60 children aged 7-17 years with JIA participated. QST assessed sensory detection threshold and pain threshold at two sites: (1) affected joint (clinically active or inactive), (2) contralateral thenar eminence. Joint site included finger, wrist, knee and ankle. Clinical status was measured using objective and subjective markers of disease severity. Questionnaires assessed pain intensity and frequency, functional disability, anxiety, pain catastrophization and fatigue. QST data collected from joints were compared within JIA patients: active vs. inactive inflammation; and data from the contralateral thenar eminence were compared between JIA and healthy control cohorts in Europe [EU, (n = 151)] and the US (n = 92). Statistical analyses were performed using Kruskal-Wallis with Dunn's post-hoc comparison, Mann-Whitney or Fisher's exact test, where appropriate.ResultsOverall, children with JIA reported low pain scores and low degrees of functional disability. Sensory detection thresholds and pain thresholds were similar in "active" compared to "inactive" joints. Despite this, children with JIA had generalized hypersensitivity at the thenar eminence when compared to healthy children for pressure (vs. EU p < 0.001), light touch (vs. EU p < 0.001), cold (vs EU, p < 0.01; vs US, p < 0.001) and heat pain (vs EU, p < 0.05; vs US p < 0.001).ConclusionsJIA is associated with increased sensitivity to painful mechanical and thermal stimuli, even in absence of pain reports, or markers of disease activity. Future research investigating mechanisms underlying pain hypersensitivity in JIA is warranted; this will in turn guide pharmacologic and non-pharmacologic interventions to prevent or reverse these processes.

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.

Project description:Objectives/hypothesisTo determine the sensory function of both sides of the face in patients with acute or chronic facial palsy.Study designProspective observational study.MethodsThe standardized quantitative sensory testing (QST) protocol of the German Research Network on Neuropathic Pain (DFNS), including thermal or mechanical stimuli (touch, pain, vibration, and pressure), was used to investigate somatosensory function in the faces of patients. A patient-reported outcome measures for the assessment of disturbed facial comfort or facial pain, the facial Clinimetric Evaluation Scale (FaCE) Facial Comfort Subscale, and the 36-Item Short Form Survey (SF-36) pain subdomain were used.ResultsA total of 29 patients (22 female, median age of 48 years; 7 acute palsy; 22 chronic palsy; House-Brackmann grade II-VI) were included. The median FaCE Facial Comfort Subscale score and the median SF-36 pain subdomain score were 50 and 100, respectively. Most patients had, at an individual level, a normal sensory function in all or most tests. On average, the frequencies for all parameters were not different between the paretic side and the contralateral side (all p > 0.05). Additionally, when z-scores were used to compare our patient sample with healthy controls from the DFNS reference database, there was no difference between the paretic side and the contralateral side (all p > 0.05). Furthermore, there were no differences between patients with acute facial palsy and those with chronic facial palsy (all p > 0.05). The FaCE Facial Comfort Subscale score and the SF-36 pain subdomain score did not correlate with the QST parameters (all p > 0.05).ConclusionPatients with acute or chronic unilateral peripheral facial palsy had normal sensory function on the paretic and contralateral sides compared with the reference values of healthy controls, and there was no significant difference between the sides. The numbness frequently felt in the affected hemiface is not related to a peripheral sensory disorder and is most likely a manifestation of an unsolved cortical somatosensory-motor mismatch.

Project description:BackgroundTo study for the first-time, pain perception, pain sensitivity, and self-reported pain in young adults with long disease duration of juvenile idiopathic arthritis (JIA) compared with controls.MethodsChildren from Central Norway diagnosed with JIA between 1997 and 2004 were included consecutively in a population-based prospective study. Children with onset 1997-2000 were part of the Nordic JIA cohort. Controls were age- and sex-matched. In 2015-2017, study visits with investigator-blinded quantitative sensory testing (QST) comprising cold and warm detection thresholds (CDT/WDT), cold and heat pain thresholds (CPT/HPT), pressure pain threshold (PPT), and a suprathreshold heat pain test were performed. We constructed separate multilevel models for each variable of detection and pain thresholds with interaction between groups and site adjusted for the effect of age and sex.ResultsAmong 96 young adults with JIA, 71% were female, median age was 22.7 years, disease duration was 16.1 years, and 47% had oligoarticular disease. Among 109 controls, 71% were female, and median age was 23.5 years. Participants with JIA had lower pressure pain thresholds (PPTs) (95% CI) compared to controls, upper limb 888 (846,930) versus 1029 (999,1059) kPa and lower limb 702 (670,734) versus 760 (726,794) kPa. Participants with inactive disease had the lowest PPTs and cold pain thresholds (CPTs), compared to those in remission off medication and those with active disease. Minor differences were found regarding CDT/WDT and CPT/HPT in JIA compared to controls. The median (IQR) temperature needed to evoke pain = 6 on a 0-10 numeric rating scale (NRS) in the suprathreshold heat pain tests were lower in JIA than in controls (46 °C (45-47 °C) versus 47 °C (46-48 °C)). We found no associations between self-reported pain and pain thresholds.ConclusionsOur results indicate for the first time that young adults with long disease duration of JIA may have altered pain perception and sensitivity compared to controls. A clinical implication may be the importance of early treatment to quickly achieve pain-free remission and avoid long-term pain sensitization.

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Multimodal hypersensitivity derived from quantitative sensory testing predicts pelvic pain outcome: an observational cohort study.

Abstract

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Multimodal hypersensitivity derived from quantitative sensory testing predicts pelvic pain outcome: an observational cohort study.

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