The journal of pain : official journal of the American Pain Society
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Randomized Controlled Trial Multicenter Study
Viscerosomatic facilitation in a subset of IBS patients, an effect mediated by N-methyl-D-aspartate receptors.
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder in which the pathophysiological mechanisms of the pain and hypersensitivity are incompletely understood. IBS patients frequently complain of pain in body regions somatotopically distinct from the gut, suggesting involvement of central hyperalgesic mechanisms. We tested the role of tonic peripheral impulse input by using both repetitive thermal stimuli to the leg and repetitive stimuli to the rectum. Changes in thermal/visceral pain sensitivity after nociceptive thermal/visceral repetitive stimulation were determined. A subset of IBS patients showed enhanced rectal/thermal pain sensitivity after repetitive thermal/rectal stimulation, respectively. IBS patients then received 60 mg dextromethorphan and placebo (diphenhydramine) in a randomized, double-blind, crossover trial. The results showed that 1) a subset of IBS patients had increased visceral/cutaneous hypersensitivity following a series of repetitive nociceptive stimuli and that 2) this increased pain sensitivity was blocked by administration of dextromethorphan. This is the first human study indicating that repetitive stimulation enhances a bidirectional mechanism of secondary hyperalgesia due to viscerosomatic facilitation in IBS patients. These unique findings elucidate mechanisms of somatic hypersensitivity in IBS patients and support an etiologic basis for abnormal N-methyl-D-aspartate receptor mechanisms that may be the target of future therapies for IBS. ⋯ Repetitive stimulation enhances a bidirectional mechanism of secondary hyperalgesia due to viscerosomatic convergence in IBS patients. The findings elucidate unique mechanisms of somatic/visceral hypersensitivity in a subset of IBS patients and further support an etiologic basis for abnormal N-methyl-D-aspartate receptor mechanisms that may be future targets of therapies for IBS.
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The current study examined the Fear Avoidance (FA) model of chronic pain in pediatric chronic pain patients. Multiple structural equation models were tested in the current study with pairwise parameter comparisons made between younger children (8-12 years) and adolescents (13-17 years). Within a sample of 350 children and adolescents, we examined functional disability and depressive symptoms in separate models with the following predictor variables-pain, pain catastrophizing, fear of pain, and avoidance of activities-after controlling for duration of pain. For a subset of patients (n = 151), we also tested a brief prospective outcome model with baseline predictor variables and functional disability at 1-month follow-up. The FA models predicting functional disability concurrently and prospectively were an excellent fit to the data. The theorized FA model for depression was a poor fit. When the model was modified to include direct pathways from the cognitive processes of pain catastrophizing and fear of pain to depressive symptoms, the model fit was significantly improved. In the examination of developmental differences between younger children and adolescent patients, duration of pain contributed to the model for younger children, whereas pain-related fears were more influential for adolescent patients. ⋯ The FA model of chronic pain appears to be applicable for pediatric patients with some modification to account for developmental differences across childhood. We discuss the developmental, theoretical, and clinical implications of these results.
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Cortical pain processing is associated with large-scale changes in neuronal connectivity, resulting from neural plasticity phenomena of which brain-derived neurotrophic factor (BDNF) is a central driver. The common single nucleotide polymorphism Val66Met is associated with reduced BDNF activity. Using the trigeminal pain-related evoked potential (tPREP) to repeated electrical painful stimuli, we investigated whether the methionine substitution at codon 66 of the BDNF gene was associated with changes in cortical processing of noxious stimuli. Fifty healthy volunteers were genotyped: 30 were Val/Val and 20 were Met-carriers. tPREPs to 30 stimuli of the right supraorbital nerve using a concentric electrode were recorded. The N2 and P2 component latencies and the N2-P2 amplitude were measured over the 30 stimuli and separately, by dividing the measurements in 3 consecutive blocks of 10 stimuli. The average response to the 30 stimuli did not differ in latency or amplitude between the 2 genotypes. There was a decrease in the N2-P2 amplitude between first and third block in the Val/Val group but not in Met-carriers. BDNF Val66Met is associated with reduced decremental response to repeated electrical stimuli, possibly as a result of ineffective mechanisms of synaptic memory and brain plasticity associated with the polymorphism. ⋯ BDNF Val66Met polymorphism affects the tPREP N2-P2 amplitude decrement and influences cortical pain processing through neurotrophin-induced neural plasticity, or through a direct BDNF neurotransmitter-like effect. Our findings suggest that upcoming BDNF central agonists might in the future play a role in pain management.
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The cold pressor task (CPT) is an ethical experimental pain task widely used by pediatric pain researchers to examine a variety of important theoretical and clinical questions. The purpose of this systematic review was to describe contemporary use of the CPT in pediatric pain research to identify possible methodological and procedural inconsistencies and inform future research. All papers using the CPT to examine pain-related outcomes in children ≤18 years old published after 2005 were identified, 2005 being when published pediatric CPT studies were last reviewed and guidelines for pediatric use of the CPT were published. Information related to samples, CPT methodology, and pain outcomes was recorded. Thirty-six published papers, involving 2,242 children (aged 3-18 years) from both healthy and clinical samples, met review inclusion criteria. Several aspects of CPT methodology with significant potential to impact pain outcomes were found to be inconsistently implemented and reported, including water temperature, use of informed versus uninformed ceilings, and the presence of observers during the CPT. Self-report child pain intensity and pain tolerance were common outcomes. A number of refinements for use of the CPT in pediatric pain research are suggested. ⋯ The cold pressor task is a commonly used experimental method in pediatric pain research. This systematic review reveals important methodological inconsistencies in its use and suggestions for improvements to previously published guidelines.
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Vestibulodynia, the most common type of chronic vulvovaginal pain, impairs the psychological, physical health of nearly 10% of women at some point in their lifetime. The aim of this investigation was to establish reliable standardized methodologies for assessment of pain sensitivity in vulvar mucosa and pelvic musculature. We enrolled 34 women with vestibulodynia and 21 pain-free controls. The participants underwent a nuanced exam that consisted of palpation of precisely located vulvar mucosal and pelvic muscle sites. These measurements remained highly stable when participants were reexamined after 2 weeks, with high within-examiner correlation. Vestibulodynia patients reported greater sensitivity than pain-free controls at the majority of examination sites, particularly at mucosal sites on the lower vestibule. The pain threshold measures at the lower mucosal sites were also associated with the participants' self-reported pain levels during intercourse. These mucosal pain threshold measurements were used to discriminate between vestibulodynia cases and controls with high sensitivity and specificity. This data supports the feasibility of contemporaneous assessment of vulvar mucosa and underlying musculature in the pelvic region, offering the hope of a more precise case definition for vestibulodynia and related disorders. ⋯ This study describes performance characteristics of novel methodologies for assessing pelvic muscle and mucosal sensitivity. These pain sensitivity measures were reproducible and associated with subjective pain reports and vestibulodynia case status and represent an important step toward a more precise case definition for vestibulodynia and related disorders.