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Pain May 2023Sleep loss heightens pain sensitivity, but the pathways underlying this association are not known. Given that experimental sleep disruption induces increases in cellular... (Randomized Controlled Trial)
Randomized Controlled Trial
Sleep loss heightens pain sensitivity, but the pathways underlying this association are not known. Given that experimental sleep disruption induces increases in cellular inflammation as well as selective loss of slow wave, N3 sleep, this study examined whether these mechanisms contribute to pain sensitivity following sleep loss in healthy adults. This assessor-blinded, cross-over sleep condition, single-site, randomized clinical trial enrolled 95 healthy adults (mean [SD] age, 27.8 [6.4]; female, 44 [53.7%]). The 2 sleep conditions were 2 nights of undisturbed sleep (US) and 2 nights of sleep disruption or forced awakening (FA, 8 pseudorandomly distributed awakenings and 200 minutes wake time during the 8-hour sleep opportunity), administered in a cross-over design after 2 weeks of washout and in a random order (FA-US; US-FA). Primary outcome was heat pain threshold (hPTH). Sleep architecture was assessed by polysomnography, and morning levels of cellular inflammation were evaluated by Toll-like receptor-4 stimulated monocyte intracellular proinflammatory cytokine production. As compared with US, FA was associated with decreases in the amount of slow wave or N3 sleep ( P < 0.001), increases in Toll-like receptor-4 stimulated production of interleukin-6 and tumor necrosis factor-α ( P = 0.03), and decreases in hPTH ( P = 0.02). A comprehensive causal mediation analysis found that FA had an indirect effect on hPTH by decreases in N3 sleep and subsequent increases in inflammation (estimate=-0.15; 95% confidence interval, -0.30 to -0.03; P < 0.05) with the proportion mediated 34.9%. Differential loss of slow wave, N3 sleep, and increases in cellular inflammation are important drivers of pain sensitivity after sleep disruption.Clinical Trials Registration: NCT01794689.
Topics: Adult; Humans; Female; Pain Threshold; Sleep Deprivation; Sleep; Pain; Sleep Initiation and Maintenance Disorders; Inflammation; Toll-Like Receptors
PubMed: 36314570
DOI: 10.1097/j.pain.0000000000002811 -
Journal of Medical Internet Research Jul 2022Virtual reality hypnosis (VRH) is a promising tool to reduce pain. However, the benefits of VRH on pain perception and on the physiological expression of pain require... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Virtual reality hypnosis (VRH) is a promising tool to reduce pain. However, the benefits of VRH on pain perception and on the physiological expression of pain require further investigation.
OBJECTIVE
In this study, we characterized the effects of VRH on the heat pain threshold among adult healthy volunteers while monitoring several physiological and autonomic functions.
METHODS
Sixty healthy volunteers were prospectively included to receive nociceptive stimulations. The first set of thermal stimuli consisted of 20 stimulations at 60°C (duration 500 milliseconds) to trigger contact heat evoked potentials (CHEPs). The second set of thermal stimuli consisted of ramps (1°C/second) to determine the heat pain threshold of the participants. Electrocardiogram, skin conductance responses, respiration rate, as well as the analgesia nociception index were also recorded throughout the experiment.
RESULTS
Data from 58 participants were analyzed. There was a small but significant increase in pain threshold in VRH (50.19°C, SD 1.98°C) compared to that in the control condition (mean 49.45°C, SD 1.87; P<.001, Wilcoxon matched-pairs signed-rank test; Cohen d=0.38). No significant effect of VRH on CHEPs and heart rate variability parameters was observed (all P>0.5; n=22 and n=52, respectively). During VRH, participants exhibited a clear reduction in their autonomic sympathetic tone, as shown by the lower number of nonspecific skin conductance peak responses (P<.001, two-way analysis of variance; n=39) and by an increase in the analgesia nociception index (P<.001, paired t-test; n=40).
CONCLUSIONS
The results obtained in this study support the idea that VRH administration is effective at increasing heat pain thresholds and impacts autonomic functions among healthy volunteers. As a nonpharmacological intervention, VRH has beneficial action on acute experimental heat pain. This beneficial action will need to be evaluated for the treatment of other types of pain, including chronic pain.
Topics: Adult; Biomarkers; Cross-Over Studies; Humans; Hypnosis; Pain; Pain Threshold; Prospective Studies; Virtual Reality
PubMed: 35904872
DOI: 10.2196/33255 -
European Journal of Pain (London,... May 2022Central neuropathic pain (CNP) is an excruciating condition, prevalent in up to a third of patients with multiple sclerosis (MS). Identifying CNP among MS patients is...
BACKGROUND
Central neuropathic pain (CNP) is an excruciating condition, prevalent in up to a third of patients with multiple sclerosis (MS). Identifying CNP among MS patients is particularly challenging considering the ample comorbid chronic pain conditions and sensory disturbances entailed by the disease. The aim was to identify sensory features unique to CNP beyond those of chronic pain and MS.
METHODS
Participants were 112 MS patients: 44 with a diagnosis of CNP, 28 with a diagnosis of chronic musculoskeletal pain (MSP), and 40 pain free. Participants underwent testing of thermal and mechanical thresholds, thermal grill illusion (TGI), pain adaptation (PA), and offset analgesia (OA), and chronic pain was characterized. A two-step cluster analysis was performed, and the association between the cluster membership and the clinical group membership (CNP, MSP, pain free) was evaluated.
RESULTS
The CNP and MSP groups were similar in most of the chronic pain variables (e.g., severity, location and quality) and MS-related variables (e.g., type, severity and medication intake). The three created clusters had unique sensory features: (1) 'Hyposensitivity' (increased thermal and touch thresholds) characterized the CNP group; (2) 'Poor inhibition and hyperalgesia' (worst PA and OA and decreased TGI threshold) characterized the MSP group; and (3) 'Efficient inhibition' (best PA and OA, smallest sensory loss) characterized the pain-free group.
CONCLUSIONS
The unique sensory features of CNP and MSP provide insight into their pathophysiology, and evaluating them may increase the ability to provide individually based interventions. Efficient inhibition may protect MS patients from chronic pain.
SIGNIFICANCE
Cluster analysis among patients with multiple sclerosis (MS) revealed that while central neuropathic pain is associated with thermal and mechanical hypoesthesia, musculoskeletal pain is involved with reduced pain inhibition and hyperalgesia; sensory profiles that provide insights into the mechanisms of these conditions and may promote an individually based pain management.
Topics: Chronic Pain; Cluster Analysis; Humans; Hyperalgesia; Illusions; Multiple Sclerosis; Musculoskeletal Pain; Neuralgia; Pain Measurement; Pain Threshold
PubMed: 35263811
DOI: 10.1002/ejp.1934 -
Pain Medicine (Malden, Mass.) Jan 2016The current study aimed to explore relationships among self-reported menstrual pain ratings, acute laboratory pain, pain catastrophizing, and anxiety sensitivity in a...
OBJECTIVES
The current study aimed to explore relationships among self-reported menstrual pain ratings, acute laboratory pain, pain catastrophizing, and anxiety sensitivity in a sample of girls without pain (No Pain group) and girls with a chronic pain condition (Chronic Pain group).
SETTING
A laboratory at an off-campus Medical School office building.
SUBJECTS
Eighty-four postmenarchal girls (43 No Pain, 41 Chronic Pain) ages 10-17 participated in the study.
METHODS
All participants completed self-report questionnaires assessing menstrual pain, pain catastrophizing, and anxiety sensitivity and completed a cold pressor task. Pain intensity during the task was rated on a 0 (no pain) to 10 (worst pain possible) numeric rating scale.
RESULTS
After controlling for age, average menstrual pain ratings (without medication) were significantly correlated with cold pressor pain intensity for the No Pain group only. In the Chronic Pain group, menstrual pain ratings were significantly correlated with pain catastrophizing and anxiety sensitivity. In a multiple linear regression analysis, after controlling for age, only pain catastrophizing emerged as a significant predictor of menstrual pain ratings in the Chronic Pain group.
CONCLUSION
Results demonstrate differences in relationships among menstrual pain, acute laboratory pain, and psychological variables in girls with no pain compared with girls with chronic pain. In addition, pain catastrophizing may be a particularly salient factor associated with menstrual pain in girls with chronic pain that warrants further investigation.
Topics: Adaptation, Psychological; Adolescent; Anxiety; Catastrophization; Chronic Pain; Dysmenorrhea; Female; Humans; Pain Measurement; Pain Threshold; Self Report; Surveys and Questionnaires
PubMed: 26218344
DOI: 10.1111/pme.12869 -
Physiological Research Dec 2017In recent years, epidemiological data has shown an increasing number of young people who deliberately self-injure. There have also been parallel increases in the number...
In recent years, epidemiological data has shown an increasing number of young people who deliberately self-injure. There have also been parallel increases in the number of people with tattoos and those who voluntarily undergo painful procedures associated with piercing, scarification, and tattooing. People with self-injury behaviors often say that they do not feel the pain. However, there is no information regarding pain perception in those that visit tattoo parlors and piercing studios compared to those who don't. The aim of this study was to compare nociceptive sensitivity in four groups of subjects (n=105, mean age 26 years, 48 women and 57 men) with different motivations to experience pain (i.e., with and without multiple body modifications) in two different situations; (1) in controlled, emotionally neutral conditions, and (2) at a "Hell Party" (HP), an event organized by a piercing and tattoo parlor, with a main event featuring a public demonstration of painful techniques (burn scars, hanging on hooks, etc.). Pain thresholds of the fingers of the hand were measured using a thermal stimulator and mechanical algometer. In HP participants, information about alcohol intake, self-harming behavior, and psychiatric history were used in the analysis as intervening variables. Individuals with body modifications as well as without body modifications had higher thermal pain thresholds at Hell Party, compared to thresholds measured at control neutral conditions. No such differences were found relative to mechanical pain thresholds. Increased pain threshold in all HP participants, irrespectively of body modification, cannot be simply explained by a decrease in the sensory component of pain; instead, we found that the environment significantly influenced the cognitive and affective component of pain.
Topics: Adolescent; Adult; Body Piercing; Female; Hot Temperature; Humans; Male; Pain Measurement; Pain Threshold; Tattooing; Young Adult
PubMed: 29355376
DOI: 10.33549/physiolres.933804 -
Psychophysiology Sep 2019Self-regulatory (SR) ability is an important resource for managing pain, but chronic pain patients experience chronic self-regulatory fatigue even when they are not in...
Self-regulatory (SR) ability is an important resource for managing pain, but chronic pain patients experience chronic self-regulatory fatigue even when they are not in pain. Pressure pain thresholds (PPT) and pain inhibition are two mechanisms that differentiate people with and without chronic pain. It was hypothesized that trait SR ability would be associated with higher PPT and better pain inhibition and that PPT and pain inhibition would be lower following high versus low SR fatigue. Three studies tested these hypotheses. Study 1 had 240 pain-free undergraduates complete measures of trait SR ability and PPT; 122 also provided data on pain inhibition. Study 2 had 38 of Study 1's participants return for two additional sessions in which they underwent PPT testing under conditions of high or low SR fatigue (within-person, counterbalanced). Study 3 repeated these procedures with pain inhibition as the outcome (n = 39). Results revealed that individual differences in SR ability were not associated with PPT or pain inhibition (all ps > 0.05). Within people, neither PPT (F(1, 36) = 1.57, p = 0.22) nor pain inhibition (F(1, 37) = 1.79, p = 0.19) were significantly different under conditions of low versus high SR fatigue. Results do not support the hypotheses that PPT or pain inhibition associate with individual differences in trait SR ability or transient changes in state SR fatigue in the absence of pain. Instead, the SR deficits in chronic pain patients may arise from the experience of chronic pain.
Topics: Adult; Aptitude; Executive Function; Fatigue; Female; Heart Rate; Humans; Individuality; Inhibition, Psychological; Male; Pain Perception; Pain Threshold; Self-Control; Students; Touch Perception; Universities; Young Adult
PubMed: 31049991
DOI: 10.1111/psyp.13388 -
Journal of Back and Musculoskeletal... 2024Central sensitization cannot be demonstrated directly in humans. Therefore, studies used different proxy markers (signs, symptoms and tools) to identify factors assumed... (Review)
Review
BACKGROUND
Central sensitization cannot be demonstrated directly in humans. Therefore, studies used different proxy markers (signs, symptoms and tools) to identify factors assumed to relate to central sensitization in humans, that is, Human Assumed Central Sensitization (HACS). The aims of this systematic review were to identify non-invasive objective markers of HACS and the instruments to assess these markers in patients with fibromyalgia (FM).
METHODS
A systematic review was conducted with the following inclusion criteria: (1) adults, (2) diagnosed with FM, and (3) markers and instruments for HACS had to be non-invasive. Data were subsequently extracted, and studies were assessed for risk of bias using the quality assessment tools developed by the National Institute of Health.
RESULTS
78 studies (n= 5234 participants) were included and the findings were categorized in markers identified to assess peripheral and central manifestations of HACS. The identified markers for peripheral manifestations of HACS, with at least moderate evidence, were pain after-sensation decline rates, mechanical pain thresholds, pressure pain threshold, sound 'pressure' pain threshold, cutaneous silent period, slowly repeated evoked pain sensitization and nociceptive flexion reflex threshold. The identified markers for central manifestations of HACS were efficacy of conditioned pain modulation with pressure pain conditioning and brain perfusion analysis. Instruments to assess these markers are: pin-prick stimulators, cuff-algometry, repetitive pressure stimulation using a pressure algometer, sound, electrodes and neuroimaging techniques.
CONCLUSIONS
This review provides an overview of non-invasive markers and instruments for the assessment of HACS in patients with FM. Implementing these findings into clinical settings may help to identify HACS in patients with FM.
Topics: Fibromyalgia; Humans; Central Nervous System Sensitization; Pain Threshold; Biomarkers; Pain Measurement
PubMed: 38073369
DOI: 10.3233/BMR-220430 -
Scandinavian Journal of Pain Apr 2022Conditioned pain modulation (CPM) is a psychophysical parameter that is used to reflect the efficacy of endogenous pain inhibition. CPM reliability is important for... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Conditioned pain modulation (CPM) is a psychophysical parameter that is used to reflect the efficacy of endogenous pain inhibition. CPM reliability is important for research and potential clinical applications. The aim of this systematic review and meta-analysis was to evaluate the reliability of CPM tests in healthy individuals and chronic pain patients.
METHODS
We searched three databases for peer-reviewed studies published from inception to October 2020: EMBASE, Web of Science and NCBI. Risk of bias and the quality of the included studies were assessed. A meta-analysis with a random effects model was conducted to estimate intraclass correlation coefficients (ICCs).
RESULTS
Meta-analysis was performed on 25 papers that examined healthy participants (=21) or chronic pain patients (=4). The highest CPM intra-session reliability was with pressure as test stimulus (TS) and ischemic pressure (IP) or cold pressor test (CPT) as conditioning stimulus (CS) in healthy individuals (ICC 0.64, 95% CI 0.45-0.77), and pressure as TS with CPT as CS in patients (ICC 0.77, 95% CI 0.70-0.82). The highest inter-session ICC was with IP as TS and IP or CPT as CS (ICC 0.51, 95% CI 0.42-0.59) in healthy subjects. The only data available in patients for inter-session reliability were with pressure as TS and CPT as CS (ICC 0.44, 95% CI 0.11-0.69). Quality ranged from very good to excellent using the QACMRR checklist. The majority of the studies (24 out of 25) scored inadequate in Kappa coefficient reporting item of the COSMIN-ROB checklist.
CONCLUSIONS
Pressure and CPT were the TS and CS most consistently associated with good to excellent intra-session reliability in healthy volunteers and chronic pain patients. The inter-session reliability was fair or less for all modalities, both in healthy volunteers and chronic pain patients.
Topics: Chronic Pain; Conditioning, Psychological; Humans; Pain Measurement; Pain Threshold; Reproducibility of Results
PubMed: 35142147
DOI: 10.1515/sjpain-2021-0149 -
European Journal of Pain (London,... Sep 2017Placebo effects on pain are reliably observed in the literature. A core mechanism of these effects is response expectancies. Response expectancies can be formed by... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Placebo effects on pain are reliably observed in the literature. A core mechanism of these effects is response expectancies. Response expectancies can be formed by instructions, prior experiences and observation of others. Whether mental imagery of a response can also induce placebo-like expectancy effects on pain has not yet been studied systematically.
METHODS
In Study 1, 80 healthy participants were randomly allocated to (i) response imagery or (ii) control imagery. In Study 2, 135 healthy participants were randomly allocated to (i) response imagery with a verbal suggestion regarding its effectiveness, (ii) response imagery only, or (iii) no intervention. In both studies, expected and experienced pain during cold pressor tests were measured pre- and post-intervention, along with psychological and physiological measures.
RESULTS
Participants rated pain as less intense after response imagery than after control imagery in Study 1 (p = 0.044, ηp2 = 0.054) and as less intense after response imagery (with or without verbal suggestion) than after no imagery in Study 2 (p < 0.001, ηp2 = 0.154). Adding a verbal suggestion did not affect pain (p = 0.068, ηp2 = 0.038). The effects of response imagery on experienced pain were mediated by expected pain.
CONCLUSIONS
Thus, in line with research on placebo effects, the current findings indicate that response imagery can induce analgesia, via its effects on response expectancies.
SIGNIFICANCE
The reported studies extend research on placebo effects by demonstrating that mental imagery of reduced pain can induce placebo-like expectancy effects on pain.
Topics: Adult; Analgesia; Cold Temperature; Female; Humans; Imagery, Psychotherapy; Male; Pain; Pain Threshold; Placebo Effect; Suggestion; Young Adult
PubMed: 28421648
DOI: 10.1002/ejp.1035 -
Cell Reports Methods Dec 2023Pain in rodents is often inferred from their withdrawal from noxious stimulation. Threshold stimulus intensity or response latency is used to quantify pain sensitivity....
Pain in rodents is often inferred from their withdrawal from noxious stimulation. Threshold stimulus intensity or response latency is used to quantify pain sensitivity. This usually involves applying stimuli by hand and measuring responses by eye, which limits reproducibility and throughput. We describe a device that standardizes and automates pain testing by providing computer-controlled aiming, stimulation, and response measurement. Optogenetic and thermal stimuli are applied using blue and infrared light, respectively. Precise mechanical stimulation is also demonstrated. Reflectance of red light is used to measure paw withdrawal with millisecond precision. We show that consistent stimulus delivery is crucial for resolving stimulus-dependent variations in withdrawal and for testing with sustained stimuli. Moreover, substage video reveals "spontaneous" behaviors for consideration alongside withdrawal metrics to better assess the pain experience. The entire process was automated using machine learning. RAMalgo (reproducible automated multimodal algometry) improves the standardization, comprehensiveness, and throughput of preclinical pain testing.
Topics: Mice; Animals; Pain Measurement; Reproducibility of Results; Pain; Pain Threshold; Behavior, Animal
PubMed: 37992707
DOI: 10.1016/j.crmeth.2023.100650