Experimental Pain Studies Research Articles

Combining Hypnosis and Virtual Reality: A Qualitative Investigation of User Experience During an Experimental Pain Study.

Virtual reality (VR) and hypnosis (H) are useful pain management tools, but the potential benefit of their combination (VRH) has yet to be studied. This study examines the user experience of VRH, compared to H and VR alone, using interviews following an experimental study examining the effect of the three interventions on pain perception. Following a within-subjects repeated measures experimental design, 16 participants received the three interventions during which they received painful electrical stimuli. Following each intervention, explanatory interviews were conducted to allow participants to elaborate on their user experience. A thematic analysis was conducted on the data collected. Three themes emerged from the interviews: (1) satisfaction: participants mostly had positive feelings toward the three modalities, with the most beneficial effects on relaxation expressed for H. (2) Body perception and attention focus: immersion in the VR and VRH conditions was appreciated. Participants described their perceptions of pain perception during the 3 conditions. (3) Device acceptability: H was the most liked, followed by VRH, and then VR alone. Intention of use was reported following the same order. The data collected highlighted participants' opinions of these different interventions and suggested adjustments for future development of the VRH intervention in pain management.

Pressure algometry in the general adult population: Age and sex differences.

Experimental pain studies have revealed inter-individual variations in pain perception that are influenced by age, sex, and country of origin. This study aimed to explore the age and sex differences in pressure pain thresholds within the Iranian general population. To assess the pressure pain thresholds, a handheld pressure algometer was applied bilaterally to the middle fingers of both hands. The participants also completed the short form of the McGill Pain Questionnaire to provide a clinical pain rating. This cross-sectional study included 1610 adult subjects (54.96% female, mean age 40.13 ± 10.18 years). The findings indicated that females generally exhibited lower pain thresholds than males when assessing pain detection and tolerance parameters (P < .001). Females also demonstrated a significant lower pressure thresholds and clinical pain ratings compared with men (P < .001). Additionally, significant differences were observed between age groups in terms of pain detection and tolerance thresholds (P = .02 and P = .03, respectively). However, the interaction between sex and age was not significant. No significant differences in pain detection thresholds were observed between the right and left hand (P = .11). This study underscores the potential utility of algometry as a valuable tool for objectifying pain in the Iranian population.

Pain catastrophizing in the elderly: An experimental pain study.

Pain catastrophizing in the aging population has not been studied in great detail. Existing investigations have reported conflicting results on the effects of age on pain catastrophizing in relation to pain responses. This study investigated the relationship between pain catastrophizing, and its individual components (rumination, magnification, and helplessness), and the responses to standardized experimental pain stimuli in old and young, healthy adults. Sixty-six volunteers (32 old: 65-87, 18 females; 34 young: 20-35, 17 females) participated in the study. Pain catastrophizing including the components of rumination, magnification, and helplessness was assessed with the pain catastrophizing scale (PCS). Experimental pain was induced by applying predefined pressure stimulations to the trapezius muscle. Pain intensity and unpleasantness were assessed using numerical rating scales. Pain catastrophizing levels and pain responses were statistically compared between the two age groups. Elderly individuals reported significantly (p = 0.028) lower scores of pain catastrophizing (Med = 5; interquartile range [IQR] = 14) than younger individuals; this difference was driven by the significantly lower components of rumination (Med = 2; IQR = 4; p = 0.017) and helplessness (Med = 2; IQR = 7; p = 0.049). A larger proportion of young (57.8%) rated pain catastrophizing at high levels, with scores above the 75th percentile (Med = 20). Additionally, elderly reported the lowest pain intensity (Med = 5; p = 0.034) and pain unpleasantness (Med = 4.5; p = 0.011) responses to the experimental pressure stimuli. In the elderly group, pain unpleasantness was positively and significantly associated with pain catastrophizing (r s = 0.416, p = 0.021), rumination (r s = 0.42, p = 0.019), and helplessness (r s = 0.434, p = 0.015), respectively. No associations were found in the young group. Elderly reported lower PCSs than young adults. Rumination and helplessness were reduced in the elderly group. The elderly population showed positive correlations between catastrophizing levels and pain unpleasantness to standardized pressure pain stimuli. Results supported the view that elderly possess resilience over specific domains of pain catastrophizing that could counteract pain perception due to physiological decline.

Nocebo effects in visceral pain: concept and design of the experimental randomized-controlled pain study 'NoVis'.

The role of psychological factors in the pathophysiology and treatment of chronic visceral pain in disorders of gut-brain interactions (DGBI) is increasingly appreciated. Placebo research has underscored that expectations arising from the psychosocial treatment context and from prior experiences shape treatment responses. However, effects of negative expectations, i.e., nocebo effects, as they are likely crucial elements of DGBI patients' clinical reality, have thus far only rarely been investigated in the context of visceral pain, with untapped potential for improved prevention and treatment. The experimental randomized-controlled pain study "NoVis," carried out within the Collaborative Research Center (CRC) 289 ("Treatment Expectation"), aims to close gaps regarding the generation and persistence of nocebo effects in healthy volunteers. It is designed to elucidate effects of negative expectations in a multiple-threat paradigm with intensity-matched rectal distensions and cutaneous thermal stimuli, allowing to test nocebo effects in the visceral and somatic pain modalities. Negative expectations are experimentally induced by elements of doctor-patient communication (i.e., instruction) and/or by surreptitious amplification of symptom intensity (i.e., experience/learning) within a treatment context. Accordingly, the repeated measures between-subject design contains the between-group factors "treatment instruction" (negative vs. control) and "treatment experience" (negative vs. control), with volunteers randomized into four experimental groups undergoing several pain stimulation phases (repeated factor). This allows to compare the efficacy of instruction vs. experience, and more importantly, their combined effects on the magnitude of negative expectations and their impact on pain responses, which we expect will be greatest for the visceral modality. After a Baseline, short-term effects are assessed during a test phase accomplished on study day 1 (Test-1 Phase). To explore the persistence of effects, a second test phase is accomplished 1 week later (Test-2 Phase). Effects of negative expectations within and across pain modalities are assessed at the subjective and objective levels, with a focus on psychophysiological and neuroendocrine measures related to stress, fear, and anxiety. Since nocebo effects can play a considerable role in the generation, maintenance, or worsening of chronic visceral pain, and may even constitute risk factors for treatment failure, knowledge from experimental nocebo research has potential to improve treatment outcomes in DGBI and other clinical conditions associated with chronic visceral pain.

Objective Measurement of Subjective Pain Perception with Autonomic Body Reactions in Healthy Subjects and Chronic Back Pain Patients: An Experimental Heat Pain Study.

Multiple attempts to quantify pain objectively using single measures of physiological body responses have been performed in the past, but the variability across participants reduces the usefulness of such methods. Therefore, this study aims to evaluate whether combining multiple autonomic parameters is more appropriate to quantify the perceived pain intensity of healthy subjects (HSs) and chronic back pain patients (CBPPs) during experimental heat pain stimulation. HS and CBPP received different heat pain stimuli adjusted for individual pain tolerance via a CE-certified thermode. Different sensors measured physiological responses. Machine learning models were trained to evaluate performance in distinguishing pain levels and identify key sensors and features for the classification task. The results show that distinguishing between no and severe pain is significantly easier than discriminating lower pain levels. Electrodermal activity is the best marker for distinguishing between low and high pain levels. However, recursive feature elimination showed that an optimal subset of features for all modalities includes characteristics retrieved from several modalities. Moreover, the study's findings indicate that differences in physiological responses to pain in HS and CBPP remain small.

Evaluation of EEG as a reliable measure of pain: an experimental pain study

Evaluation of EEG as a reliable measure of pain: an experimental pain study

Evaluation of EEG as a reliable measure of pain: an experimental pain study

Evaluation of EEG as a reliable measure of pain: an experimental pain study

The contribution of autonomic mechanisms to pain in temporomandibular disorders: A narrative review.

Temporomandibular disorders (TMD) are diagnosed based on symptom presentation and, like other functional pain disorders, often lack definitive pathology. There is a strong association between elevated stress levels and the severity of TMD-related pain, which suggests that alterations in autonomic tone may contribute to this pain condition. This narrative review examines the association between altered autonomic function and pain in TMD. Relevant articles were identified by searching PubMed and through the reference list of those studies. TMD sufferers report an increased incidence of orthostatic hypotension. As in other chronic musculoskeletal pain conditions, TMD is associated with increased sympathetic tone, diminished baroreceptor reflex sensitivity and decreased parasympathetic tone. It remains to be determined whether ongoing pain drives these autonomic changes and/or is exacerbated by them. To examine whether increased sympathetic tone contributes to TMD-related pain through β2 adrenergic receptor activation, clinical trials with the beta blocker propranolol have been undertaken. Although evidence from small studies suggested propranolol reduced TMD-related pain, a larger clinical trial did not find a significant effect of propranolol treatment. This is consistent with human experimental pain studies that were unable to demonstrate an effect of β2 adrenergic receptor activation or inhibition on masticatory muscle pain. In preclinical models of temporomandibular joint arthritis, β2 adrenergic receptor activation appears to contribute to inflammation and nociception, whereas in masticatory muscle, α1 adrenergic receptor activation has been found to induce mechanical sensitisation. Some agents used to treat TMD, such as botulinum neurotoxin A, antidepressants and α2 adrenergic receptor agonists, may interact with the autonomic nervous system as part of their analgesic mechanism. Even if dysautonomia turns out to be a consequence rather than a causative factor of painful TMD, the study of its role has opened up a greater understanding of the pathogenesis of this condition.

To Calibrate or not to Calibrate? A Methodological Dilemma in Experimental Pain Research

To calibrate or not to calibrate? This question is raised by almost everyone designing an experimental pain study with supra-threshold stimulation. The dilemma is whether to individualize stimulus intensity to the pain threshold / supra-threshold pain level of each participant or whether to provide the noxious stimulus at a fixed intensity so that everyone receives the identical input. Each approach has unique pros and cons which need to be considered to i) accurately design an experiment, ii) enhance statistical inference in the given data and, iii) reduce bias and the influence of confounding factors in the individual study e.g., body composition, differences in energy absorption and previous experience. Individualization requires calibration, a procedure already irritating the nociceptive system but allowing to match the pain level across individuals. It leads to a higher variability of the stimulus intensity, thereby influencing the encoding of “noxiousness” by the central nervous system. Results might be less influenced by statistical phenomena such as ceiling/floor effects and the approach does not seem to rise ethical concerns. On the other hand, applying a fixed (standardized) intensity reduces the problem of intensity encoding leading to a large between-subjects variability in pain responses. Fixed stimulation intensities do not require pre-exposure. It can be proposed that one method is not preferable over another, however the choice depends on the study aim and the desired level of external validity. This paper discusses considerations for choosing the optimal approach for experimental pain studies and provides recommendations for different study designs. PerspectiveTo calibrate pain or not? This dilemma is related to almost every experimental pain research. The decision is a trade-off between statistical power and greater control of stimulus encoding. The article decomposes both approaches and presents the pros and cons of either approach supported by data and simulation experiment.

Opioid-sparing effect of cannabinoids for analgesia: an updated systematic review and meta-analysis of preclinical and clinical studies

Cannabinoid co-administration may enable reduced opioid doses for analgesia. This updated systematic review on the opioid-sparing effects of cannabinoids considered preclinical and clinical studies where the outcome was analgesia or opioid dose requirements. We searched Scopus, Cochrane Central Registry of Controlled Trials, Medline, and Embase (2016 onwards). Ninety-two studies met the search criteria including 15 ongoing trials. Meta-analysis of seven preclinical studies found the median effective dose (ED50) of morphine administered with delta-9-tetrahydrocannabinol was 3.5 times lower (95% CI 2.04, 6.03) than the ED50 of morphine alone. Six preclinical studies found no evidence of increased opioid abuse liability with cannabinoid administration. Of five healthy-volunteer experimental pain studies, two found increased pain, two found decreased pain and one found reduced pain bothersomeness with cannabinoid administration; three demonstrated that cannabinoid co-administration may increase opioid abuse liability. Three randomized controlled trials (RCTs) found no evidence of opioid-sparing effects of cannabinoids in acute pain. Meta-analysis of four RCTs in patients with cancer pain found no effect of cannabinoid administration on opioid dose (mean difference −3.8 mg, 95% CI −10.97, 3.37) or percentage change in pain scores (mean difference 1.84, 95% CI −2.05, 5.72); five studies found more adverse events with cannabinoids compared with placebo (risk ratio 1.13, 95% CI 1.03, 1.24). Of five controlled chronic non-cancer pain trials; one low-quality study with no control arm, and one single-dose study reported reduced pain scores with cannabinoids. Three RCTs found no treatment effect of dronabinol. Meta-analyses of observational studies found 39% reported opioid cessation (95% CI 0.15, 0.64, I2 95.5%, eight studies), and 85% reported reduction (95% CI 0.64, 0.99, I2 92.8%, seven studies). In summary, preclinical and observational studies demonstrate the potential opioid-sparing effects of cannabinoids in the context of analgesia, in contrast to higher-quality RCTs that did not provide evidence of opioid-sparing effects.

Recent advances in nanoplatforms for the treatment of neuropathic pain.

Narrative review. The objective was to summarize the literature on nanoplatforms in spinal cord injury (SCI) and describe their effect in facilitating experiments for SCI. Currently, the primary clinical treatment for neuropathic pain (NP) is drug therapy, but these traditional drugs have many disadvantages, such as high dose, rapid clearance from the circulatory system, off-target side effects, and cytotoxicity. Moreover, the treatment for NP is complicated by the existence of blood-brain barrier. In recent years, nanomedicine has been receiving increased attention; this novel modality could help deliver drugs to treat NP via nanoplatforms, making it a promising alternative therapy. The use of nanoplatforms can enhance pharmaceutic effectiveness by either avoiding rapid clearance from the blood or ensuring adequate concentration in the lesion. A literature review was conducted, with a focus on nanoplatforms that have been described in the experimental studies of neuropathic pain. We provide a brief description of the roles of liposomes, polymeric nanoparticles, metal nanoparticles, micelles, and dendrimers in the treatment of NP and discuss the prospective development of the nanoplatform system for NP. The emergence of various nanoplatform drug delivery systems can provide an advantageous resource tool for real-time diagnosis and effective treatment of SCI-related NP.

Cerebral processing of sharp mechanical pain measured with arterial spin labeling.

IntroductionArterial spin labeling (ASL) is a functional neuroimaging technique that has been frequently used to investigate acute pain states. A major advantage of ASL as opposed to blood‐oxygen‐level‐dependent functional neuroimaging is its applicability for low‐frequency designs. As such, ASL represents an interesting option for studies in which repeating an experimental event would reduce its ecological validity. Whereas most ASL pain studies so far have used thermal stimuli, to our knowledge, no ASL study so far has investigated pain responses to sharp mechanical pain.MethodsAs a proof of concept, we investigated whether ASL has the sensitivity to detect brain activation within core areas of the nociceptive network in healthy controls following a single stimulation block based on 96 s of mechanical painful stimulation using a blunt blade.ResultsWe found significant increases in perfusion across many regions of the nociceptive network such as primary and secondary somatosensory cortices, premotor cortex, posterior insula, inferior parietal cortex, parietal operculum, temporal gyrus, temporo‐occipital lobe, putamen, and the cerebellum. Contrary to our hypothesis, we did not find any significant increase within ACC, thalamus, or PFC. Moreover, we were able to detect a significant positive correlation between pain intensity ratings and pain‐induced perfusion increase in the posterior insula.ConclusionWe demonstrate that ASL is suited to investigate acute pain in a single event paradigm, although to detect activation within some regions of the nociceptive network, the sensitivity of our paradigm seemed to be limited. Regarding the posterior insula, our paradigm was sensitive enough to detect a correlation between pain intensity ratings and pain‐induced perfusion increase. Previous experimental pain studies have proposed that intensity coding in this region may be restricted to thermal stimulation. Our result demonstrates that the posterior insula encodes intensity information for mechanical stimuli as well.

Commentary to "Challenges and opportunities in translational pain research-An opinion paper of the working group on translational pain research of the European Pain Federation (EFIC)" by Mouraux et al.

Preclinical and clinical pain science have since long suffered from lack of joint ventures that, as securely as possible, have approached problems that are relevant for the understanding of clinical pain phenomenologies and treatment (Yezierski & Hansson, 2018), the core of translational pain medicine. The uncoupling of the two has led to loss of momentum and few novel efficacious treatment remedies where needed the most, i.e., in long term pain states. Here, the area of translational pain medicine is craving for a road map so that preclinical and clinical scientists can walk hand in hand into the future with a common agenda on how to approach the search for much needed improved treatment strategies.

Experimentally evoked pain in Alzheimer's disease.

Pain continues to be underrecognized and undertreated in Alzheimer's disease (AD) while existing guidance about pain assessment and management in dementia is not widespread. Brain regions involved in pain processing and modulation are damaged during AD, and the pain experience in AD is not well understood. Experimental pain studies using psychophysics can further our understanding of the pain experience in AD, which may lead to improved assessment and management of pain in people living with AD. A systematic review was conducted to explicate the current understanding of experimentally evoked pain in AD from primary research using psychophysical methods. Peer-reviewed publications were found via PubMed, CINAHL, and PsycINFO. A total of 18 primary research, peer-reviewed full articles that met inclusion criteria were included, representing 929 total participants. Experimentally evoked pain in people with AD demonstrates that despite cognitive impairment and a reduced ability to effectively communicate, individuals with AD experience pain similar to or more unpleasant than cognitively intact older adults. This may mean amplified pain unpleasantness in people with AD. Our current best practices need to be widely disseminated and put into clinical practice. Self-report of pain continues to be the gold standard, but it is ineffective for noncommunicative patients and those unable to understand pain scales or instructions because of memory/cognitive impairment. Instead, pain treatment should be ethically initiated based on patient reports and behaviors, caregiver/surrogate reports, review of the medical record for painful conditions, analgesic trials, and regular reassessments.

Acute experimentally-induced pain replicates the distribution but not the quality or behaviour of clinical appendicular musculoskeletal pain. A systematic review

Abstract Objectives Experimental pain is a commonly used method to draw conclusions about the motor response to clinical musculoskeletal pain. A systematic review was performed to determine if current models of acute experimental pain validly replicate the clinical experience of appendicular musculoskeletal pain with respect to the distribution and quality of pain and the pain response to provocation testing. Methods A structured search of Medline, Scopus and Embase databases was conducted from database inception to August 2020 using the following key terms: “experimental muscle pain” OR “experimental pain” OR “pain induced” OR “induced pain” OR “muscle hyperalgesia“ OR (“Pain model” AND “muscle”). Studies in English were included if investigators induced experimental musculoskeletal pain into a limb (including the sacroiliac joint) in humans, and if they measured and reported the distribution of pain, quality of pain or response to a provocation manoeuvre performed passively or actively. Studies were excluded if they involved prolonged or delayed experimental pain, if temporomandibular, orofacial, lumbar, thoracic or cervical spine pain were investigated, if a full text of the study was not available or if they were systematic reviews. Two investigators independently screened each title and abstract and each full text paper to determine inclusion in the review. Disagreements were resolved by consensus with a third investigator. Results Data from 57 experimental pain studies were included in this review. Forty-six of these studies reported pain distribution, 41 reported pain quality and six detailed the pain response to provocation testing. Hypertonic saline injection was the most common mechanism used to induce pain with 43 studies employing this method. The next most common methods were capsaicin injection (5 studies) and electrical stimulation, injection of acidic solution and ischaemia with three studies each. The distribution of experimental pain was similar to the area of pain reported in clinical appendicular musculoskeletal conditions. The quality of appendicular musculoskeletal pain was not replicated with the affective component of the McGill Pain Questionnaire consistently lower than that typically reported by musculoskeletal pain patients. The response to provocation testing was rarely investigated following experimental pain induction. Based on the limited available data, the increase in pain experienced in clinical populations during provocative maneuvers was not consistently replicated. Conclusions Current acute experimental pain models replicate the distribution but not the quality of chronic clinical appendicular musculoskeletal pain. Limited evidence also indicates that experimentally induced acute pain does not consistently increase with tests known to provoke pain in patients with appendicular musculoskeletal pain. The results of this review question the validity of conclusions drawn from acute experimental pain studies regarding changes in muscle behaviour in response to pain in the clinical setting.

The effect of alexithymia and depressive feelings on pain perception in somatoform pain disorder

ObjectiveTo investigate the relationship between alexithymia and depression and their influence on the subjective versus experimental pain perception in somatoform pain disorder. MethodsThree groups consisting of 40 patients with somatoform pain disorder, 40 patients with depression, and 40 healthy controls were matched. They completed questionnaires regarding alexithymia (TAS26) and depressive feelings (BDI-II). In addition, pain patients rated their subjective pain intensity (NRS). Quantitative sensory testings were conducted in all participants examining temperature (CPT, HPT) and mechanical (MPT, PPT) thresholds. ResultsAnalysis of variance showed that alexithymia was significantly increased in both patient groups compared to healthy controls, but with the highest amount in somatoform pain. Regression analyses confirmed that this finding was in part due to a high comorbidity of depressive feelings in both patient groups. We found a discrepancy between increased clinical pain ratings and elevated pressure pain thresholds, indicating a less intense mechanical pain perception in somatoform pain. Correlation analyses demonstrated a significant connection of subjective pain ratings and pressure pain thresholds with depressive feelings. ConclusionContrary to the results of other experimental pain studies on chronic muskuloskeletal pain syndromes, we could not confirm central sensitization in somatoform pain disorder. Our findings place the somatoform pain disorder more in the direction of affective disorder such as depression. These findings may improve a better understanding of the disease and also have direct therapeutic implications. The high occurrence of alexithymia and depressive feelings in somatoform pain should be considered in diagnostic and therapeutic regimens of these patients.

The Role of Chronic Stress in Normal Visceroception: Insights From an Experimental Visceral Pain Study in Healthy Volunteers.

Visceroception is a complex phenomenon comprising the sensation, interpretation, and integration of sensations along the gut-brain axis, including pain or defecatory urgency. Stress is considered a crucial risk factor for the development and maintenance of disorders of gut-brain signaling, which are characterized by altered visceroception. Although the broad role of stress and stress mediators in disturbed visceroception is widely acknowledged, the putative contribution of chronic stress to variations in normal visceroception remains incompletely understood. We aimed to elucidate the role of chronic stress in shaping different facets of visceroception. From a well-characterized, large sample of healthy men and women (N = 180, 50% female), volunteers presenting with low (n = 57) and elevated (n = 61) perceived chronic stress were identified based on the validated Trier Inventory for Chronic Stress (TICS). Visceral sensitivity together with perceived and recalled intensity and defecatory urgency induced by repeated rectal distensions was experimentally assessed, and compared between low and elevated stress groups. Subgroups were compared regarding state anxiety and salivary cortisol concentrations across experimental phases and with respect to psychological measures. Finally, in the full sample and in chronic stress subgroups, a recall bias in terms of a discrepancy between the perception of experimentally-induced symptoms and their recall was tested. Participants with elevated chronic stress presented with increased state anxiety and higher cortisol concentrations throughout the experimental phases compared to the group with low chronic stress. Group differences in visceral sensitivity were not evident. The elevated stress group perceived significantly higher urgency during the stimulation phase, and recalled substantially higher feelings of urgency induced by rectal distensions, while perceived and recalled intensity were comparable between groups. Volunteers with elevated stress exhibited a recall bias in terms of a higher recall relative to mean perception of urgency, whereas no such bias was observed for the intensity of experimental visceral stimulation. Our findings in healthy men and women provide first evidence that the troublesome symptom of urgency might be particularly modifiable by chronic stress and support the relevance of memory biases in visceroception. These results may help to disentangle the impact of chronic stress on altered visceroception in disturbances of gut-brain communication.

Humani modeli eksperimentalnog bola

Pain is an unpleasant sensory experience, associated with existing or potential tissue damage. It has also strong cognitive and emotional components. Stimuli that causes pain goes through process of nociception, which includes transduction, transmission, modulation and perception of said stimuli. Depending on the type of stimuli, we can classify human experimental pain models into mechanical, electrical, thermal and chemical. Information about pain mechanisms can be obtained from the following: 1) in vitro studies, 2) animal experiments, 3) human experimental pain studies and 4) clinical studies. Chosing the appropriate method for pain evaluation is a key step in the design of pain studies. Combining it with different electro-physiological and imaging methods, it can provide better objectivity and quantification of pain mechanisms. Focus in experimental pain studies is slowly shifting from static parameters of pain, such as pain threshold and maximum tolerance, to dynamic parameters, which can give us valuable insight in function of endogenous analgesic systems. This can be done using conditioned pain modulation. Using experimental pain on healthy voulenteers is key step in switching from animal models to clinical studies, foremost for validization of data from animals, making them important in translational research. Results from experimental pain studies can help us in understanding nociceptive mechanisms of acute and chronic pain, alongside development of new therapeutic modalities.

Conditioning pain modulation reduces pain only during the first stimulation of thetemporal summation of pain paradigm in healthy participants.

Pro-nociceptive and anti-nociceptive mechanisms are commonly assessed in clinical and experimental pain studies, buttheir potential interaction is not well understood. Investigate the effect of conditioning pain modulation (CPM) on temporal summation of pain (TSP). Twenty healthy participants underwent cuff algometry assessment on the lower legs to establish the pressure pain tolerance threshold (PTT). For the TSP assessment, ten stimuli at the level of the PTT were delivered by computerised cuff inflations (1-s stimulation, 1-s break) while participants rated pain intensity on a 10-cm electronic visual analogue scale (VAS). This TSP paradigm was thenrepeated with a simultaneous conditioning stimulus induced by a cuff on the contralateral leg, inflated to a constant pressure corresponding to 30% (mild), 70% (moderate) or 100% (severe) of the PTT. These were assessed in a randomised order, with a fifteen-minute break between tests. A final TSP test without conditioning was reassessed at the end (post-recording). An interaction between stimuli (1-10) and repetition (p<0.05) was found for VAS scores. VAS scores for the first stimulus were decreased during 30%, 70%, and 100% conditioning intensities, compared to baselineand post-recordings (p<0.05). There was a significant increase in TSP during conditioning (p<0.05). There were no significant differences between baseline and post-recordings for any stimuli (p>0.05). The current study indicates that mild to severe stimuli administered by cuff algometry does not modulate summation effect of temporal summation of pain, which could indicate that pain facilitatory mechanisms are more potent compared with pain inhibitory mechanisms. Current knowledge on the interaction effect of pro and anti-nociceptive paradigms are the lacking. The current study indicates that conditioning pain modulation does not modulate thesummation effect of temporal summation of pain, when evaluated by computerized pressure algometry. This finding was independent of the mild, moderate and severe painful conditioning intensities.

Genetic components of human pain sensitivity: a protocol for a genome-wide association study of experimental pain in healthy volunteers

IntroductionPain constitutes a major component of the global burden of diseases. Recent studies suggest a strong genetic contribution to pain susceptibility and severity. Whereas most of the available evidence relies...