The journal of pain : official journal of the American Pain Society
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Current evidence supports the efficacy of placebo analgesia and illustrates that patients may be open to placebo use despite uncertainty regarding its mechanisms. Debate persists, however, concerning the ethics of placebo treatments. The purpose of the present web-based study was to expand upon the empirical literature on placebo analgesia ethics and acceptability. Participants (n = 100) provided their definition of a placebo and responded to 24 questions addressing placebo analgesia perceived knowledge, acceptability, effectiveness, and likelihood of placebo use among different health care providers. Results support previous research on the effects of placebo on negative mood and health care provider attributions, with findings illustrating that negative consequences of administration were largely mitigated by a beneficial treatment outcome. Results showed that participants conceptualized placebo as predominately inert and were mixed regarding interpretations of placebo effectiveness. Though acceptability ratings were dependent on the context of placebo administration, participants endorsing even moderate placebo acceptability were more open to placebo interventions and reported overall more positive treatment outcomes. Participants believed that placebos were used differentially among health care providers. Additional studies are needed to determine if placebo education can beneficially impact perceptions of placebo analgesia knowledge, acceptability, and treatment effectiveness. ⋯ This study presents an examination of analgesic placebo treatment perceived acceptability, efficacy, and knowledge among lay individuals. Our findings highlight the importance of assessing placebo conceptualizations and treatment perceptions in evaluating placebo ethics-a highly relevant finding that informs the clinical use of placebo components in managing pain.
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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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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 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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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.