Experimental Pain Research Articles

Examining the role of mood in pain-limited treadmill walking duration in young healthy individuals.

The purpose of the study was to examine the effects of acute mood modulation on treadmill walking duration during experimental pain application. This was a repeated measure, within-subject study design. 30 healthy individuals (Males: Females 16:14; age 22.9 ± 2.5 years; height 170.9 ± 9.5 cm; body mass 68.4 ± 14.6 kg) attended a familiarization session and three experimental sessions, whereby they simultaneously viewed emotionally evoking stimulus from the International Affective Picture System (IAPS) and performed two treadmill walking tests (maximum 10 min duration) with a fixed nociceptive input applied to the thigh (pressure cuff). The primary outcome was treadmill walking duration during pain application to achieve a fixed pain score. During walking, mood (Self-Assessment Manikin: SAM 0-9) and pain (numerical rating scale: NRS 0-10) were measured. Mood valence scores were significantly different in all conditions (p < 0.001), negative (2.4 ± 0.3), neutral (4.9 ± 0.6) and positive (6.6 ± 0.3). There was a significant difference (p = 0.04) in the treadmill walking duration for different mood states. For the primary outcome, post hoc analysis found differences between the negative and positive mood conditions for the treadmill walking durations to reach pain scores of 3 (negative: 224 ± 49 s; positive: 259 ± 60s, effect size [ES]: 0.80), 4 (negative: 262 ± 59 s; positive: 326 ± 90s, ES: 0.92), 5 (negative: 313 ± 86 s; positive: 385 ± 113 s, ES: 0.90), 6 (negative: 367 ± 106 s; positive: 447 ± 113 s, ES: 1.04) and 7 (negative: 423 ± 114 s; positive: 521 ± 110 s, ES: 1.02). There was no significant difference in the treadmill walking duration between the neutral vs negative mood and neutral vs positive mood conditions. These results highlight the potential psychophysiological impacts on the pain experience in healthy individuals and encourages pursuit in strategies to minimize pain-limited exercise, a highly prevalent issue in the chronic pain population. Walking-based rehabilitation, designed to improve physical activity, has been shown to improve pain and disability. However active participation and adherence in walking-based rehabilitation has shown to be jeopardized by pain and pain-related cognitive and behavioural adaptations. This study examined the effect of a shift in mood on pain perception and treadmill walking tolerance. We found that with a worse mood, individuals were less tolerant of pain and walked on the treadmill for a shorter duration. These results suggest that factors which improve mood should be combined with walking-based training to improve tolerance.

Deficits in neuromuscular control of increasing force in patients with chronic lateral epicondylitis.

Objective: This study investigated the neuromuscular control of increasing and releasing force in patients with chronic lateral epicondylitis (CLE). Methods: Fifteen patients with CLE (10 males, 5 females, 46.5 ± 6.3years) and fifteen healthy participants (9 males, 6 females, 45.3 ± 2.5years) participated in this study. In addition to power grip and maximal voluntary contraction (MVC) of wrist extension, force fluctuation dynamics and characteristics of inter-spike intervals (ISI) of motor units (MUs) with various recruitment thresholds in the extensor carpi radialis brevis (ECRB) and extensor carpi radialis longus (ECRL) during a designated force-tracking task with a trapezoidal target (0%-75%-0% MVC) were assessed. Results: Besides a smaller MVC of wrist extension, the patients exhibited significantly greater task errors (p = 0.007) and force fluctuations (p = 0.001) during force increment than the healthy counterparts. Nevertheless, no force variables significantly differed between groups during force release (p > 0.05). During force increment, the amplitudes of the motor unit action potential of the ECRB and ECRL muscles of the patients were smaller than those of the heathy counterparts (p < 0.001). The patient group also exhibited a higher percentage of motor units (MU) with lower recruitment threshold (<5% MVC) in the ECRL/ECRB muscles and a lower percentage of MU with higher recruitment threshold (>40% MVC) in the ECRB muscle, compared to the healthy group. During force increment, the patient group exhibited a higher rate of decrease in inter-spike intervals (ISIs) of motor units with lower recruitment thresholds (<10% MVC) in the ECRB and ECRL muscles, compared to the control group (p < 0.005). Conclusion: The patients with CLE exhibited more pronounced impairment in increasing force than in releasing force. This impairment in increasing force is attributed to deficits in tendon structure and degenerative changes in the larger motor units of the wrist extensors. To compensate for the neuromuscular deficits, the rate of progressive increase in discharge rate of the remaining smaller motor units (MUs) is enhanced to generate force. Significance: The deficits in neuromuscular control observed in CLE with degenerative changes cannot be fully explained by the experimental pain model, which predicts pain-related inhibition on low-threshold motor units.

Photobiomodulation for Correction of Systemic Disorders of Experimental Pain Syndromes

The development of anti-pain technologies in the complex treatment of pain syndromes is one of the most urgent tasks of modern medicine. We undertook a placebo-controlled experimental study of the therapeutic potential of low-intensity laser radiation when applied to acupuncture points that are directly related to the autonomic nervous system. The adaptation effect of puncture photobiomodulation on the induction of stress-mediated autonomic reactions, oxidative metabolism and microcirculation in animals during the acute phase of pain stress was revealed. The data obtained are of interest for use in the complex rehabilitation of patients with pain syndromes.

The effect of risperidone on behavioral reactions and gene expression of pro- and anti-inflammatory cytokines in neuropathic pain model induced by chronic constriction injury of the sciatic nerve in rat.

Neuropathic pain results from lesions or diseases affecting the somatosensory system. The management of a patient with chronic neuropathic pain remains a challenge several studies report the analgesic effect of serotonin receptor antagonists in different models of experimental pain. The present study was designed to study the effect of systemic administration of risperidone, on behavioral scores of neuropathic pains in chronic constriction (CCI) model in rats. Inducing neuropathic pain with the CCI model which causes heat hyperalgesia, heat, and mechanical allodynia was performed on rats, and then, in two phases, risperidone effect was determined. In the acute phase, risperidone 1, 2, 4mg was administered for three groups half an hour before behavioral tests on the 7th, 14th, and 21st day after surgery, and in the chronic phase, risperidone 1, 2, and 4mg was administered for three different groups from the 1st to 14th days after surgery than on 14th-day behavioral scores were performed. For gene expression analysis, samples are taken from spinal cord tissues in lumbar segments. This study shows chronic administration of risperidone as an antipsychotic drug was effective on heat hyperalgesia and allodynia. However, only the max dosage (4mg) of risperidone showed meaningful improvement in increasing mechanical allodynia. However, acute administering of risperidone did not show any meaningful changes in behavioral tests on neuropathic pain induced by chronic constriction injury of the sciatic nerve in rats. In addition, gene expression results showed an increase in IL-4 and IL-10 gene expression in the risperidone group compared to the sham group. This study suggests the helpful preventive effects of risperidone in developing and increasing neuropathic pain, but it does not have any instant effect.

Saffron (Crocus sativus) and its constituents for pain management: A review of current evidence.

Pain can become a chronic and deliberating experience with a significant burden. In preclinical and clinical studies, Saffron (Crocus sativus L.) has shown analgesic activities. Considering the unsatisfactory results of current therapeutic management for chronic pain conditions, we aimed to review saffron's analgesic activity and underlying mechanisms. Saffron showed antinociceptive activities in formalin-, carrageenan-, and capsaicin-induced experimental pain models. Saffron analgesic activities affected several targets, including ion channels of nociceptors; the adrenergic system and central histaminic system; inhibition of inflammatory pathways, apoptotic pathways, and oxidative stress; regulation of NO pathway, and the endocannabinoid system. Clinical studies showed analgesia of Saffron in rheumatoid arthritis, after-pain following childbirth, dysmenorrhea, and fibromyalgia. Our literature review showed that saffron can be beneficial as an adjunct therapy to commonly used analgesics in practice, particularly in chronic pain conditions.

Acute pain drives different effects on local and global cortical excitability in motor and prefrontal areas: insights into interregional and interpersonal differences in pain processing.

Pain-related depression of corticomotor excitability has been explored using transcranial magnetic stimulation-elicited motor-evoked potentials. Transcranial magnetic stimulation-electroencephalography now enables non-motor area cortical excitability assessments, offering novel insights into cortical excitability changes during pain states. Here, pain-related cortical excitability changes were explored in the dorsolateral prefrontal cortex and primary motor cortex (M1). Cortical excitability was recorded in 24 healthy participants before (Baseline), during painful heat (Acute Pain), and non-noxious warm (Warm) stimulation at the right forearm in a randomized sequence, followed by a pain-free stimulation measurement. Local cortical excitability was assessed as the peak-to-peak amplitude of early transcranial magnetic stimulation evoked potential, whereas global-mean field power measured the global excitability. Relative to the Baseline, Acute Pain decreased the peak-to-peak amplitude in M1 and dorsolateral prefrontal cortex compared with Warm (both P < 0.05). A reduced global-mean field power was only found in M1 during Acute Pain compared with Warm (P = 0.003). Participants with the largest reduction in local cortical excitability under Acute Pain showed a negative correlation between dorsolateral prefrontal cortex and M1 local cortical excitability (P = 0.006). Acute experimental pain drove differential pain-related effects on local and global cortical excitability changes in motor and non-motor areas at a group level while also revealing different interindividual patterns of cortical excitability changes, which can be explored when designing personalized treatment plans.

Pain-Related Stigma and Its Associations With Clinical and Experimental Pain Severity in Youth With Chronic Musculoskeletal Pain Conditions.

Many children with chronic musculoskeletal pain conditions experience stigma which can have negative downstream consequences. This study compares ratings of clinical pain (current pain intensity and pain interference), experimental pain (temporal summation, cold water tolerance, and cold pain intensity), and pain-related stigma among three groups of youth with rheumatic conditions. The relations among ratings of pain-related stigma and pain variables were explored. Eighty-eight youth aged 8-17 years with a diagnosis of juvenile idiopathic arthritis (JIA = 32), juvenile fibromyalgia (JFM = 31), or non-specific chronic pain (NSCP = 25) completed measures of clinical pain ratings (average 7-day pain intensity, day of assessment pain (DoA), and pain interference), experimental pain (cold pain tolerance, cold pain intensity, and temporal summation of mechanical pain), and pain-related stigma. Data analysis compared pain-related stigma and pain ratings across the three groups and examined the relations among pain-related stigma and pain ratings. Youth with JFM reported higher ratings of clinical pain and pain-related stigma than their counterparts with NSCP or JIA. However, there were no differences in experimental pain. Pain-related stigma was associated with greater ratings of pain interference, particularly for those with JIA and NSCP. Pain-related stigma was also associated with greater average daily pain intensity but not DoA. Youth with medically unexplained pain report greater stigma and worse pain than their peers; thus, robust assessment of pain in this population is necessary. Future work should longitudinally explore the impact of pain-related stigma on pain outcomes and treatment responses.

Pain history and experimental pressure pain responses in adolescents: Results from a population-based birth cohort.

Sensitized pain mechanisms are often reported in musculoskeletal pain conditions, but population-based paediatric studies are lacking. We assessed whether adolescents with musculoskeletal pain history had evidence of increased responsiveness to experimental pressure stimuli. Data were from 1496 adolescents of the Generation XXI birth cohort. Pain history was collected using the Luebeck Pain Questionnaire (self-reported at 13, parent-reported at 7 and 10 years). Two case definitions for musculoskeletal pain were considered: (1) cross-sectional-musculoskeletal pain lasting more than 3 months at age 13 and (2) longitudinal-musculoskeletal pain at age 13 with musculoskeletal pain reports at ages 7 and/or 10. Lower limb cuff pressure algometry was used to assess pain detection and tolerance thresholds, conditioned pain modulation effects (CPM, changes in thresholds in the presence on painful conditioning) and temporal summation of pain effects (TSP, changes in pain intensity to 10 phasic painful cuff stimulations). Adolescents with musculoskeletal pain at age 13 plus a history of pain in previous evaluations (longitudinal definition) had lower pain tolerance thresholds compared to the remaining sample (40.2 v. 49.0 kPa, p = 0.02), but showed no differences in pain detection threshold, CPM effect and TSP effect. Pain sensitivity, CPM effects and TSP effects were not significantly different when the current pain only case definition (cross-sectional) was used. Adolescents with current musculoskeletal pain who had a history of pain since childhood had lower tolerance to cuff stimulation. This may suggest long-standing musculoskeletal pain since childhood may contribute to sensitisation, rather than the presence of current pain only. Repeated musculoskeletal pain up to age 13 years may contribute to higher pain sensitivity (particularly lowered pressure pain tolerance) in the general adolescent population. This does not seem to be the case when reported pain experiences are recent or when the outcomes are temporal pain summation or CPM. In this community-based paediatric sample, the vast majority showed no sign of altered pain processing, but a small fraction may reveal some pain sensitization at 13 years of age.

Changes in sex hormones and their interactions are related to pain perception between different menstrual subphases.

Background Whether sex hormones are related to pain perception across the menstrual cycle is unclear. We examined changes in experimental pain perception in healthy young females between the early-to mid-follicular subphase (emF) and the mid-luteal subphase (mL) and explored the role of sex hormones. Methods 66 participants were finally involved in the study. We tested pressure pain, cold pain, ischemic pain and needle pain meanwhile measured sex hormones levels in two menstrual subphases. Results Only the right ulna pressure test showed a significant reduction in pain threshold (PPTh3) during the mL. The absolute change of PPTh3 (PPTh3mL -PPTh3emF) was related to the absolute change of prolactin. The relative change of the range of pain tolerance for pressure pain of the right ulna (RPT3rc) was related to the relative change of progesterone (Prc) and estradiol(E2rc) levels, and the interaction effects showed that at Prc≤30, E2rc was positively correlated with RPT3rc. The same, the relative change of pressure pain tolerance of the pulp of the middle finger on the right hand (PPTo4rc) was related to E2rc and Prc, and the results of the interaction between E2rc and Prcsuggest that when E2rc is ≤0.8, Prc is positively correlated with PPTo4rc. Conclusions Two different formulas were applied in this study and showed inconsistent results. Most pain tests showed no difference between two subphases of menstrual cycle. Only the relative changes of the PPTo4 and RPT3 are related to the E2rc and Prc respectively between menstrual subphase in an interactive way in healthy young women.

Persistent Contralateral Pain Compromises Exercise Tolerance but Does not Alter Corticomotor Responses During Repeated, Submaximal Isometric Knee Extensions to Task Failure

Muscle pain is an important determinant of exercise tolerance, but its relationship with neurophysiological responses during a submaximal exercise trial is unclear. The purpose of this study was to determine the effect of persistent contralateral pain on neurophysiological function and perceptual responses during ipsilateral isometric knee extensions to task failure. Ten participants performed a single-leg repeated submaximal isometric knee extensions with (PAIN) or without (CTRL) constant pain induced by intermittent blood flow occlusion combined with evoked muscle contraction applied to the contralateral, resting leg. Transcranial magnetic stimulation (TMS) applied over the motor cortex was used to assess corticospinal excitability (quantified as motor evoked potentials), corticospinal inhibition (quantified as silent period duration), and short interval intracortical inhibition. Maximal voluntary contractions (MVCs), coupled with femoral nerve stimulation to the exercising leg, were performed every 12 submaximal contractions to assess neuromuscular function. Perceived leg pain and effort were also assessed throughout the exercise. The experimental pain shortened the time to task failure compared to CTRL (P = 0.019). Although time effects were present, no differences appeared between conditions for MVC force, voluntary activation, or potentiated twitch force across both tasks (all P > 0.05). Additionally, no differences between CTRL and PAIN were demonstrated for any TMS-derived measures assessing corticospinal responses. Exercising leg pain was higher in CTRL (P = 0.018), as was perceived exertion (P = 0.030). Overall, when using a persistent, submaximal experimental pain intervention, it appears that although muscle pain compromises exercise tolerance, this phenomenon occurs independently of potential alterations in corticomotor mechanisms.

Priming of the autonomic nervous system after an experimental human pain model.

Modulated autonomic responses to noxious stimulation have been reported in experimental and clinical pain. These effects are likely mediated by nociceptive sensitization, but may also, more simply reflect increased stimulus-associated arousal. To disentangle between sensitization- and arousal-mediated effects on autonomic responses to noxious input, we recorded sympathetic skin responses (SSRs) in response to 10 pinprick and heat stimuli before (PRE) and after (POST) an experimental heat pain model to induce secondary hyperalgesia (EXP) and a control model (CTRL) in 20 healthy females. Pinprick and heat stimuli were individually adapted for pain perception (4/10) across all assessments. Heart rate (HR), heart rate variability (HRV) and skin conductance (SCL) were assessed before, during, and after the experimental pain model. Both pinprick- and heat-induced SSRs habituated from PRE to POST in CTRL, but not EXP (p=0.033). Background SCL (during stimuli application) was heightened in EXP compared to CTRL condition during pinprick and heat stimuli (p=0.009). Our findings indicate that enhanced SSRs after an experimental pain model are neither fully related to subjective pain, as SSRs dissociated from perceptual responses, nor to nociceptive sensitization, as SSRs were enhanced after both modalities. Our findings can, however, be explained by priming of the autonomic nervous system during the experimental pain model, which makes the autonomic nervous system more susceptible to noxious input. Taken together, autonomic readouts have the potential to objectively assess not only nociceptive sensitization, but also priming of the autonomic nervous system, which may be involved in the generation of distinct clinical pain phenotypes.

Low-dose naltrexone for treatment of pain in patients with fibromyalgia: a randomized, double-blind, placebo-controlled, crossover study.

Fibromyalgia (FM) is a chronic fluctuating, nociplastic pain condition. Naltrexone is a µ-opioid-receptor antagonist; preliminary studies have indicated a pain-relieving effect of low-dose naltrexone (LDN) in patients with FM. The impetus for studying LDN is the assumption of analgesic efficacy and thus reduction of adverse effects seen from conventional pharmacotherapy. First, to examine if LDN is associated with analgesic efficacy compared with control in the treatment of patients with FM. Second, to ascertain the analgesic efficacy of LDN in an experimental pain model in patients with FM evaluating the competence of the descending inhibitory pathways compared with controls. Third, to examine the pharmacokinetics of LDN. The study used a randomized, double-blind, placebo-controlled, crossover design and had a 3-phase setup. The first phase included baseline assessment and a treatment period (days -3 to 21), the second phase a washout period (days 22-32), and the third phase a baseline assessment followed by a treatment period (days 33-56). Treatment was with either LDN 4.5 mg or an inactive placebo given orally once daily. The primary outcomes were Fibromyalgia Impact Questionnaire revised (FIQR) scores and summed pain intensity ratings (SPIR). Fifty-eight patients with FM were randomized. The median difference (IQR) for FIQR scores between LDN and placebo treatment was -1.65 (18.55; effect size = 0.15; P = 0.3). The median difference for SPIR scores was -0.33 (6.33; effect size = 0.13; P = 0.4). Outcome data did not indicate any clinically relevant analgesic efficacy of the LDN treatment in patients with FM.

Physiological response to pain in female adolescents with nonsuicidal self-injury as a function of severity

BackgroundPreliminary evidence indicates altered hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS) response to experimental pain in individuals with nonsuicidal self-injury (NSSI). This study investigated effects of NSSI severity and severity of psychopathology on the HPA axis and ANS response to pain. MethodsN = 164 adolescents with NSSI and n = 45 healthy controls received heat pain stimulation. Salivary cortisol, α-amylase and blood pressure were repeatedly assessed before and after painful stimulation. Heart rate (HR) and heart rate variability (HRV) were assessed continuously. NSSI severity and comorbid psychopathology were derived from diagnostic assessments. Main and interaction effects of time of measurement and NSSI severity, adjusted for severity of adverse childhood experiences, borderline personality disorder and depression, on HPA axis and ANS response to pain were examined using regression analyses. ResultsIncreasing NSSI severity predicted an increasing cortisol response (χ2(3) = 12.09, p = .007) to pain. After adjusting for comorbid psychopathology, greater NSSI severity predicted decreased α-amylase levels following pain (χ2(3) = 10.47, p = .015), and decreased HR (χ2(2) = 8.53, p = .014) and increased HRV(χ2(2) = 13.43, p = .001) response to pain. LimitationsFuture research should implement several NSSI severity indicators, potentially revealing complex associations with the physiological response to pain. Assessing physiological responses to pain in NSSI in a naturalistic setting presents a promising avenue for future research in NSI. ConclusionsFindings indicate an increased pain-related HPA axis response and an ANS response characterized by reduced sympathetic and increased parasympathetic activity associated with NSSI severity. Results support claims for dimensional approaches to NSSI and its related psychopathology alongside shared, underlying neurobiological correlates.

PainVision-based evaluation of brain potentials: a novel approach for quantitative pain assessment.

Introduction: The complex and multidimensional nature of pain poses a major challenge in clinical pain assessments. In this study, we aimed to evaluate a novel approach combining quantitative sensory testing (QST) with event-related potential measurements for assessment of experimental pain in healthy individuals. Methods: QST was performed with a commercial device (PainVision, PS-2100), and numeric rating scale (NRS) scores after exposure to different sensory stimuli were reported by the participants. Resting-state electroencephalography (EEG) was simultaneously performed to capture the cortical responses to peripheral stimulation. Results: Pain scores increased with the intensity of stimuli, with mean NRS scores of 2.7 ± 1.0 after mild stimuli and 5.6 ± 1.0 after moderate stimuli. A reproducible, significant P2-N2 complex was evoked by both mild and moderately painful stimuli, but not by non-painful stimuli. The latency of pain-related potentials was not significantly different between stimuli. The amplitudes of both P2 and N2 components significantly increased when intense nociception was applied, and the increments mainly originated from theta oscillations. Conclusion: The combination of QST with EEG was feasible for subjective and objective pain assessment. Distinct patterns of brain potentials were associated with the phenotype of the peripheral stimuli (e.g., noxious versus. innoxious, high versus. low pain intensity).

Intra- and interindividual reliability of muscle pain induced by an intramuscular injection of hypertonic saline injection into the quadriceps.

Intramuscular injections of hypertonic saline are commonly used to induce experimental muscle pain, but reliability data on this technique are lacking. This study investigated the intra- and interindividual reliability of pain measures from a hypertonic saline injection into the vastus lateralis. Fourteen healthy participants (6 female) attended three laboratory visits where they received an intramuscular injection of 1 mL hypertonic saline into the vastus lateralis. Changes in pain intensity were recorded on an electronic visual analogue scale, and pain quality was assessed after pain had resolved. Reliability was assessed with the coefficient of variation (CV), minimum detectable change (MDC) and intraclass correlation coefficient (ICC) with 95% CIs. Mean pain intensity displayed high levels of intraindividual variability (CV = 16.3 [10.5-22.0]%) and 'poor' to 'very good' relative reliability (ICC = 0.71 [0.45-0.88]) but had a MDC of 11 [8-16] au (out of 100). Peak pain intensity exhibited high levels of intraindividual variability (CV = 14.8 [8.8-20.8]%) with 'moderate' to 'excellent' levels of relative reliability (ICC = 0.81 [0.62-0.92]), whereas the MDC was 18 [14-26] au. Measures of pain quality exhibited good reliability. Interindividual variability in pain measures was high (CV > 37%). Intramuscular injections of 1 mL of hypertonic saline into the vastus lateralis display substantial levels of interindividual variability, but MDC is below the clinically important changes in pain. This model of experimental pain is suitable for studies involving repeated exposures. Many pain research studies have performed intramuscular injections of hypertonic saline to investigate responses to muscle pain. However, the reliability of this technique is not well established. We examined the pain response over three repeated sessions of a hypertonic saline injection. The pain induced by hypertonic saline has considerable interindividual variability but has largely acceptable intraindividual reliability. Therefore, the injections of hypertonic saline to induce muscle pain are a reliable model of experimental muscle pain.

Habituation to Pain in Patients with Chronic Pain: Clinical Implications and Future Directions

In this review, the latest insights into habituation to pain in chronic pain are summarized. Using a systematic search, results of studies on the evidence of habituation to (experimental) pain in migraine, chronic low back pain, fibromyalgia, and a variety of chronic pain indications are presented. In migraine, reduced habituation based on self-report and the EEG-based N1 and N2–P2 amplitude is reported, but the presence of contradictory results demands further replication in larger, well-designed studies. Habituation to pain in chronic low back pain seems not to differ from controls, with the exception of EEG measures. In fibromyalgia patients, there is some evidence for reduced habituation of the N2–P2 amplitude. Our analysis shows that the variability between outcomes of studies on habituation to pain is high. As the mechanisms underlying habituation to pain are still not fully understood and likely involve several pathways, it is now too early to conclude that habituation to pain is related to clinical outcomes and can be used as a diagnostic marker. The review ends with a discussion on future directions for research including the use of standard outcome measures to improve comparisons of habituation to pain in patients and controls, as well as a focus on individual differences.

Experimental Pain Picture System (EPPS): Development and Validation

Pain-related pictures are useful for studying how individuals respond to pain-related stimulation. Such pictures can occasionally be found in databases for affective pictures. However, a validated database specifically for pain-related pictures is not available yet. In 2 experiments (N = 185 and 103, respectively), we developed and validated the Experimental Pain Pictures System (EPPS). In both experiments, negative valence, arousal, and painfulness ratings were compared between neutral-, sad-, and pain-related pictures. The pain-related pictures represented both deep and superficial somatic pain. Across the 2 experiments, pain-related pictures were judged as more negative, arousing, and painful than neutral pictures and more painful than sad pictures. The final EPPS contains 50 pictures of different painful events considered moderately to highly painful by participants. The EPPS is a valuable tool for studying pain-related responses, as it gives researchers a choice among many validated pictures depicting different types of pain, increasing the comparability between studies. PerspectiveThis article presents the validation of the experimental pain pictures system, which consists of a set of pain-related pictures. The experimental pain pictures system is composed of pictures depicting different types of pain. Participants rated all the pictures as being negative, arousing, and painful.

The role of the male rat infralimbic cortex in distraction analgesia

Cognitive interventions, including distraction, have been successfully utilized in the manipulation of experimental pain and the treatment of clinical pain. Attentional diversions can reduce the experience of pain, a phenomenon known as distraction analgesia (DA). Prior research has suggested that variations in stimulus intensity may influence the magnitude of DA. However, the neural substrates of DA remain largely unknown. Converging evidence suggests that the infralimbic cortex (IL) in the brains of rats may contribute to the phenomenon of DA. The function of the rat IL in DA has never been directly investigated, therefore, this study sought to identify the role of the IL at two levels of noxious stimulus intensity among brain-intact and IL lesioned male rats within an established rat model of DA. A distractor object reduced formalin-induced nociceptive behavior in brain-intact rats, and this DA effect was detectable during low- (0.5% formalin) and high-intensity (1% formalin) stimulation. IL lesion resulted in a near-complete elimination of the DA effect and an overall reduction in formalin pain. These results provide the first known evidence that (i) the IL is involved in processing DA in rats, (ii) the IL contributes to formalin-induced nociceptive behavior irrespective of distraction, and (iii) a high-intensity stimulation was generally more susceptible to DA than low-intensity stimulation. These findings may further inform the mechanisms and future development of non-pharmacological strategies to reduce pain.

The Biology of Placebo and Nocebo Effects on Experimental and Chronic Pain: State of the Art.

(1) Background: In recent years, placebo and nocebo effects have been extensively documented in different medical conditions, including pain. The scientific literature has provided strong evidence of how the psychosocial context accompanying the treatment administration can influence the therapeutic outcome positively (placebo effects) or negatively (nocebo effects). (2) Methods: This state-of-the-art paper aims to provide an updated overview of placebo and nocebo effects on pain. (3) Results: The most common study designs, the psychological mechanisms, and neurobiological/genetic determinants of these phenomena are discussed, focusing on the differences between positive and negative context effects on pain in experimental settings on healthy volunteers and in clinical settings on chronic pain patients. Finally, the last section describes the implications for clinical and research practice to maximize the medical and scientific routine and correctly interpret the results of research studies on placebo and nocebo effects. (4) Conclusions: While studies on healthy participants seem consistent and provide a clear picture of how the brain reacts to the context, there are no unique results of the occurrence and magnitude of placebo and nocebo effects in chronic pain patients, mainly due to the heterogeneity of pain. This opens up the need for future studies on the topic.

Central sensitization in adolescents with hypermobility spectrum disorder or hypermobile Ehlers-Danlos syndrome—a feasibility study

BackgroundPain is a major symptom in adolescents with hypermobility spectrum disorder or hypermobile Ehlers-Danlos syndrome. Although the underlying mechanism causing generalized pain in children with hypermobility spectrum disorder or hypermobile Ehlers-Danlos syndrome is unclear, central sensitization has been suggested as a possible explanation. The aim of this study was to explore the feasibility of a study protocol for a future case–control study, investigating features of central sensitization in adolescents with hypermobility spectrum disorder or hypermobile Ehlers-Danlos syndrome.MethodsCentral sensitization features were measured in ten patients and nine healthy controls aged 13–17 years via experimental pain measurement quantifying primary and secondary hyperalgesia, endogenous pain modulation, and exercise-induced hyperalgesia. Descriptive statistics were used. Frequency, median, and range values were calculated.ResultsEleven out of 57 patients chose to participate. No control could be recruited through public schools. Therefore, a convenience sampling strategy was used for the recruitment of the control group. The process of assessing primary and secondary hyperalgesia, endogenous pain modulation, and exercise-induced hyperalgesia was well tolerated by all participants (patients and controls). When assessing endogenous pain modulation via conditioned pain modulation, two participants in the patient group and three in the control group did not achieve a pain experience ≥ 3 on the numerical rating scale when immersing their hands in cold water.ConclusionThis study investigated the feasibility, safety, and toleration of experimental pain measurements in adolescents with hypermobility spectrum disorder or hypermobile Ehlers-Danlos syndrome. Although the test protocol proved to be sufficiently feasible for use with the participant group, it will need to be adapted in the main study in order to obtain more reliable data. Recruitment, especially of participants for the control group, can be a major obstacle for future studies and requires careful planning.Trial registrationResearchweb.org, 270,501. Registered on 9 May 2019.