Transcranial Direct Current Stimulation Reduces Pressure Pain Sensitivity in Patients with Non-Malignant Chronic Pain.

OBJECTIVES: Non-malignant chronic pain is a clinical challenge because pharmacological treatment often fails to relieve pain. Transcranial direct current stimulation (tDCS) is a treatment that could have the potential for pain relief and improvement in quality of life. However, there is a lack of clinical trials evaluating the effects of tDCS on the pain system. The aim of the present study was to evaluate the effect of 5 days of anodal tDCS treatment on the pain system in chronic non-malignant pain patients using quantitative sensory testing (QST) and quality of life questionnaires: (1) Brief Pain Inventory-short form (BPI-sf), (2) European Organization for Research and Treatment of Life Questionnaire (EORTC-C30), and (3) Hospital Anxiety Depression Scale (HADS). METHODS: Eleven non-malignant chronic pain patients (51±13.6 years old, 5M) participated in the study. Anodal tDCS was applied for five consecutive days, followed by sham stimulation after a washout period of at least two weeks. Pressure pain thresholds (PPT) and pain tolerance thresholds (PTT) were assessed in different body regions on days 1 and 5. RESULTS: Anodal tDCS appeared to maintain PTT at C5 (clavicle) on day 5, but sham stimulation decreased PTT (P=0.007). Additionally, anodal tDCS increased PTT compared to sham at day 5 at Th10 ventral dermatomes (P=0.014). Both anodal and sham tDCS decreased the BPI-sf total and interference scores, and the EORTC-C30 fatigue score, but no interaction effect was observed. DISCUSSION: This study adds to the evidence in the literature that tDCS may be a potential therapeutic tool for the management of non-malignant chronic pain.

High-frequency electrical stimulation increases cortical excitability and mechanical sensitivity in a chronic large animal model.

ABSTRACT: Translational models of the sensitized pain system are needed to progress the understanding of involved mechanisms. In this study, long-term potentiation was used to develop a mechanism-based large-animal pain model. Event-related potentials to electrical stimulation of the ulnar nerve were recorded by intracranial recordings in pigs, 3 weeks before, immediately before and after, and 3 weeks after peripheral high-frequency stimulation (HFS) applied to the ulnar nerve in the right forelimb (7 pigs) or in control animals (5 pigs). Event-related potential recordings and peripheral HFS were done during anesthesia. Two weeks before and after the HFS, behavioral responses reflecting mechanical and thermal sensitivity were collected using brush, noxious limb-mounted pressure algometer, and noxious laser stimuli. The HFS intervention limb was progressively sensitized to noxious mechanical stimulation in week 1 and 2 compared with baseline (P = 0.045) and the control group (P < 0.034) but not significantly to laser or brush stimulation. The first negative (N1) peak of the event-related potential was increased 30 minutes after HFS compared with before (P < 0.05). The N1 peak was also larger compared with control pigs 20 to 40 minutes after HFS (P < 0.031) but not significantly increased 3 weeks after. The relative increase in N1 30 minutes after HFS and the degree of mechanical hyperalgesia 2 weeks post-HFS was correlated (P < 0.033). These results show for the first time that the pig HFS model resembles the human HFS model closely where the profile of sensitization is comparable. Interestingly, the degree of sensitization was associated with the cortical signs of hyperexcitability at HFS induction.

Cross-sectional experimental assessment of pain modulation as part of multidimensional profiling of people with cervicogenic headache: protocol for a feasibility study.

BACKGROUND: An endogenous pain modulation profile, reflecting antinociceptive and pronociceptive mechanisms, may help to direct management by targeting the involved pain mechanism. For individuals with cervicogenic headache (CeH), the characteristics of such profiles were never investigated. However, the individual nature of experiencing pain demands profiling within a multidimensional framework including psychosocial lifestyle characteristics. The objective of the current protocol is to assess the pain modulation profile, which includes psychosocial lifestyle characteristics among people with CeH. METHODS AND ANALYSIS: A protocol is described to map pain modulation profiles in people with CeH. A cross-sectional non-randomised experimental design will be used to assess feasibility of mapping these profiles. The pain modulation profile is composed based on results on the Depression, Anxiety, Stress Scale, Pittsburgh Sleep Quality Index, Headache Impact Test and on responses to temporal summation of pain (pinprick), conditioned pain modulation and widespread hyperalgesia (mechanical pressure pain threshold and cuff algometry). Primary analyses will report results relating to outcomes on feasibility. Secondary analyses will involve an analysis of proportions (%) of the different psychosocial lifestyle profiles and pain profiles. ETHICS AND DISSEMINATION: Ethical approval was granted by the Ethics Committee Research UZ/KU Leuven (Registration number B3222024001434) on 30 May 2024. Results will be published in peer-reviewed journals, at scientific conferences and, through press releases. Protocol V.3. protocol date: 3 June 2024.

Facilitation of Early and Middle Latency SEP after tDCS of M1: No Evidence of Primary Somatosensory Homeostatic Plasticity.

Homeostatic plasticity is a mechanism that stabilizes cortical excitability within a physiological range. Most homeostatic plasticity protocols have primed and tested the homeostatic response of the primary motor cortex (M1). This study investigated if a homeostatic response could be recorded from the primary sensory cortex (S1) after inducing homeostatic plasticity in M1. In 31 healthy participants, homeostatic plasticity was induced over M1 with a priming and testing block of transcranial direct current stimulation (tDCS) in two different sessions (anodal and cathodal). S1 excitability was assessed by early (N20, P25) and middle-latency (N33-P45) somatosensory evoked potentials (SEP) extracted from 4 electrodes (CP5, CP3, P5, P3). Baseline and post-measures (post-priming, 0-min, 10-min, and 20-min after homeostatic induction) were taken. Anodal M1 homeostatic plasticity induction significantly facilitated the N20-P25, P45 peak, and N33-P45 early SEP components up to 20-min post-induction, without any indication of a homeostatic response (i.e., reduced SEP). Cathodal homeostatic induction did not induce any significant effect on early or middle latency SEPs. M1 homeostatic plasticity induction by anodal stimulation protocol to the primary motor cortex did not induce a homeostatic response in SEPs.

Evoked oscillatory cortical activity during acute pain: Probing brain in pain by transcranial magnetic stimulation combined with electroencephalogram.

Temporal dynamics of local cortical rhythms during acute pain remain largely unknown. The current study used a novel approach based on transcranial magnetic stimulation combined with electroencephalogram (TMS-EEG) to investigate evoked-oscillatory cortical activity during acute pain. Motor (M1) and dorsolateral prefrontal cortex (DLPFC) were probed by TMS, respectively, to record oscillatory power (event-related spectral perturbation and relative spectral power) and phase synchronization (inter-trial coherence) by 63 EEG channels during experimentally induced acute heat pain in 24 healthy participants. TMS-EEG was recorded before, during, and after noxious heat (acute pain condition) and non-noxious warm (Control condition), delivered in a randomized sequence. The main frequency bands (α, ß1, and ß2) of TMS-evoked potentials after M1 and DLPFC stimulation were recorded close to the TMS coil and remotely. Cold and heat pain thresholds were measured before TMS-EEG. Over M1, acute pain decreased α-band oscillatory power locally and α-band phase synchronization remotely in parietal-occipital clusters compared with non-noxious warm (all p < .05). The remote (parietal-occipital) decrease in α-band phase synchronization during acute pain correlated with the cold (p = .001) and heat pain thresholds (p = .023) and to local (M1) α-band oscillatory power decrease (p = .024). Over DLPFC, acute pain only decreased ß1-band power locally compared with non-noxious warm (p = .015). Thus, evoked-oscillatory cortical activity to M1 stimulation is reduced by acute pain in central and parietal-occipital regions and correlated with pain sensitivity, in contrast to DLPFC, which had only local effects. This finding expands the significance of α and ß band oscillations and may have relevance for pain therapies.

Effects of pain on cortical homeostatic plasticity in humans: a systematic review.

Homeostatic plasticity (HP) is a negative feedback mechanism that prevents excessive facilitation or depression of cortical excitability (CE). Cortical HP responses in humans have been investigated by using 2 blocks of noninvasive brain stimulation with a no-stimulation block in between. A healthy HP response is characterized by reduced CE after 2 excitatory stimulation blocks and increased CE when using inhibitory stimulation. Conversely, impaired HP responses have been demonstrated in experimental and chronic pain conditions. Therefore, this systematic review aimed to provide an overview of the effect of pain on cortical HP in humans. Scopus, Embase, and PubMed were searched from inception until November 20, 2023. The included studies (1) compared experimental or clinical pain conditions with healthy controls, (2) induced HP using 2 blocks of stimulation with a no-stimulation interval, and (3) evaluated CE measures such as motor-evoked potentials. Four studies were included, consisting of 5 experiments and 146 participants, of whom 63 were patients with chronic pain and 48 were subjected to an experimental pain model. This systematic review found support for an HP impairment in pain compared with that in pain-free states, reflected by a lack of CE reduction after excitatory-excitatory HP induction over the primary motor cortex. Inhibitory-inhibitory HP induction did not produce a consistent HP response across studies, independent of pain or pain-free states. Standardization of HP induction protocols and outcome calculations is needed to ensure reproducibility and study comparison. Future HP studies may consider investigating sensory domains including nociception, which would further our understanding of abnormal HP regulation in pain conditions.

Impact of Chronic Pain on Use-Dependent Plasticity: Corticomotor Excitability and Motor Representation in Musicians With and Without Pain.

Long-term musical training induces adaptive changes in the functional representation of the motor cortex. It is unknown if the maladaptive plasticity associated with chronic pain, frequently affecting trained musicians, may alter the use-dependent plasticity in the motor cortex. This study investigated the interaction between adaptive and maladaptive plasticity in the motor pathways, in particular how chronic pain influences long-term use-dependent plasticity. Using transcranial magnetic stimulation (TMS), corticospinal excitability was assessed by measuring the amplitude of the motor-evoked potential (MEP), area of the motor map, volume, and center of gravity of the first dorsal interosseous muscle in 19 pain-free musicians, 17 upper limb/neck pain chronic pain musicians, and 19 pain-free non-musicians as controls. Motor map volume and MEP amplitude were smaller for both pain-free and chronic pain musicians compared to pain-free controls (P < 0.011). No significant differences were found between musicians with and without chronic pain. These findings confirm that long-term musical training can lead to focalized and specialized functional organization of the primary motor cortex. Moreover, the adaptive use-dependent plasticity acquired through fine-motor skill acquisition is not significantly compromised by the maladaptive plasticity typically associated with chronic pain, highlighting the potential of long-term sensorimotor training to counteract the effects of chronic pain in the motor system.

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

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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. SIGNIFICANCE: 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.

Disrupted Cortical Homeostatic Plasticity Due to Prolonged Capsaicin-induced Pain.

Homeostatic plasticity (HP) regulates cortical excitability (CE) stability but is disrupted in persistent pain conditions. This study investigated how prolonged experimental pain affects HP and if pain relief modulates disrupted HP. Twenty-four healthy participants were randomised into a PainRelief or NoPainRelief group and attended four sessions; two sessions on consecutive days, separated by two weeks. Transcranial magnetic stimulation motor-evoked potentials reflecting CE and quantitative sensory testing (QST) measures were recorded. A capsaicin (pain condition) or placebo (control condition) patch was applied to the hand. HP was induced by cathodal-cathodal transcranial direct current stimulation (HP1) with CE assessment before and after. The PainRelief group had ice applied to the patch, while the NoPainRelief group waited for five minutes; subsequently another HP induction (HP2) and CE assessment were performed. After 24 h with the patch on, HP induction (HP3), QST, and CE recordings were repeated. Capsaicin reduced CE and the pain condition showed disrupted homeostatic responses at all time points (HP1: showed CE inhibition instead of facilitation; HP2 & HP3: lack of CE facilitation). Conversely, homeostatic responses were induced at all time points for the placebo condition. Capsaicin pain disrupts HP which is not restored by ice-induced pain relief. Future research may explore the prevention of HP disruption by targeting capsaicin-induced nociception but not pain perception.

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 in Parkinson disease: mechanistic substrates, main classification systems, and how to make sense out of them.

ABSTRACT: Parkinson disease (PD) affects up to 2% of the general population older than 65 years and is a major cause of functional loss. Chronic pain is a common nonmotor symptom that affects up to 80% of patients with (Pw) PD both in prodromal phases and during the subsequent stages of the disease, negatively affecting patient's quality of life and function. Pain in PwPD is rather heterogeneous and may occur because of different mechanisms. Targeting motor symptoms by dopamine replacement or with neuromodulatory approaches may only partially control PD-related pain. Pain in general has been classified in PwPD according to the motor signs, pain dimensions, or pain subtypes. Recently, a new classification framework focusing on chronic pain was introduced to group different types of PD pains according to mechanistic descriptors: nociceptive, neuropathic, or neither nociceptive nor neuropathic. This is also in line with the International Classification of Disease-11 , which acknowledges the possibility of chronic secondary musculoskeletal or nociceptive pain due to disease of the CNS. In this narrative review and opinion article, a group of basic and clinical scientists revise the mechanism of pain in PD and the challenges faced when classifying it as a stepping stone to discuss an integrative view of the current classification approaches and how clinical practice can be influenced by them. Knowledge gaps to be tackled by coming classification and therapeutic efforts are presented, as well as a potential framework to address them in a patient-oriented manner.

Effects of conditioned pain modulation on Capsaicin-induced spreading muscle hyperalgesia in humans.

OBJECTIVES: Muscle pain can be associated with hyperalgesia that may spread outside the area of primary injury due to both peripheral and central sensitization. However, the influence of endogenous pain inhibition is yet unknown. This study investigated how endogenous pain inhibition might influence spreading hyperalgesia in experimental muscle pain. METHODS: Conditioned pain modulation (CPM) was assessed in 30 male volunteers by cold pressor test at the non-dominant hand as conditioning and pressure pain thresholds (PPT) at the dominant 2nd toe as test stimuli. Subjects were classified as having inhibitory or facilitating CPM based on published reference values. Subsequently, muscle pain and hyperalgesia were induced by capsaicin injection into the non-dominant supraspinatus muscle. Before and 5, 10, 15, 20, 30, 40, 50 and 60 min later, PPTs were recorded at the supraspinatus, infraspinatus and deltoid muscle, ring finger and toe. RESULTS: Compared to baseline, PPTs decreased at the supraspinatus, infraspinatus and deltoid muscle (p≤0.03), and increased at the finger and toe (p<0.001). In facilitating CPM (n=10), hyperalgesia occurred at 5, 10, 15, 20 and 40 min (p≤0.026). In inhibitory CPM (n=20), hyperalgesia only occurred after 10 and 15 min (p≤0.03). At the infraspinatus muscle, groups differed after 5 and 40 min (p≤0.008). CONCLUSIONS: The results suggest that facilitating CPM is associated with more spreading hyperalgesia than inhibitory CPM. This implies that poor endogenous pain modulation may predispose to muscle pain and spreading hyperalgesia after injury, and suggest that strategies to enhance endogenous pain modulation may provide clinical benefits.

Pain-free default mode network connectivity contributes to tonic experimental pain intensity beyond the role of negative mood and other pain-related factors.

BACKGROUND: Alterations in the default mode network (DMN) connectivity across pain stages suggest a possible DMN involvement in the transition to persistent pain. AIM: This study examined whether pain-free DMN connectivity at lower alpha oscillations (8-10 Hz) accounts for a unique variation in experimental peak pain intensity beyond the contribution of factors known to influence pain intensity. METHODS: Pain-free DMN connectivity was measured with electroencephalography prior to 1 h of capsaicin-evoked pain using a topical capsaicin patch on the right forearm. Pain intensity was assessed on a (0-10) numerical rating scale and the association between peak pain intensity and baseline measurements was examined using hierarchical multiple regression in 52 healthy volunteers (26 women). The baseline measurements consisted of catastrophizing (helplessness, rumination, magnification), vigilance, depression, negative and positive affect, sex, age, sleep, fatigue, thermal and mechanical pain thresholds and DMN connectivity (medial prefrontal cortex [mPFC]-posterior cingulate cortex [PCC], mPFC-right angular gyrus [rAG], mPFC-left Angular gyrus [lAG], rAG-mPFC and rAG-PCC). RESULTS: Pain-free DMN connectivity increased the explained variance in peak pain intensity beyond the contribution of other factors (ΔR2 = 0.10, p = 0.003), with the final model explaining 66% of the variation (R2 = 0.66, ANOVA: p < 0.001). In this model, negative affect (ß = 0.51, p < 0.001), helplessness (ß = 0.49, p = 0.007), pain-free mPFC-lAG connectivity (ß = 0.36, p = 0.003) and depression (ß = -0.39, p = 0.009) correlated significantly with peak pain intensity. Interestingly, negative affect and depression, albeit both being negative mood indices, showed opposing relationships with peak pain intensity. CONCLUSIONS: This work suggests that pain-free mPFC-lAG connectivity (at lower alpha) may contribute to individual variations in pain-related vulnerability. SIGNIFICANCE: These findings could potentially lead the way for investigations in which DMN connectivity is used in identifying individuals more likely to develop chronic pain.

Facilitated Central Pain Mechanisms Across the Menstrual Cycle in Dysmenorrhea and Enlarged Pain Distribution in Women With Longer Pain History.

Dysmenorrhea (DYS), or recurrent menstrual pain, is a highly prevalent pain condition among otherwise healthy women. However, the progression of DYS over time and the influence of the menstrual cycle phases need to be better understood. While the location and distribution of pain have been used to assess pain mechanisms in other conditions, they are unexplored in DYS. Thirty otherwise healthy women with severe DYS and 30 healthy control women were recruited into 3 subgroups (n = 10) according to the length of their menstrual history (<5, 5-15, or>15 years since menarche). The intensity and distribution of menstrual pain were recorded. Pressure pain thresholds at abdominal, hip, and arm sites, pressure-induced pain distribution, temporal summation of pain, and pain intensity after pressure cessation over the gluteus medius were assessed at 3 menstrual cycle phases. Compared with the healthy control women, those with DYS showed lower pressure pain thresholds in every site and menstrual cycle phase (P < .05), enlarged pressure-induced pain areas during menstruations (P < .01), and increased temporal summation and pain intensity after pressure cessation in the overall menstrual cycle (P < .05). Additionally, these manifestations were enhanced during the menstrual and premenstrual phases compared to ovulation in women with DYS (P < .01). Women with long-term DYS demonstrated enlarged pressure-induced pain distribution, enlarged menstrual pain areas, and more days with severe menstrual pain compared to the short-term DYS subgroup (P < .01). Pressure-induced and menstrual pain distributions were strongly correlated (P < .001). These findings suggest that severe DYS is a progressive condition underscored by facilitated central pain mechanisms associated with pain recurrence and exacerbation. PERSPECTIVE: Enlarged pressure-induced pain areas occur in DYS, associated with the length of the condition and the distribution of menstrual pain. Generalized hyperalgesia is present throughout the entire menstrual cycle and intensifies during premenstrual and menstrual phases.

Level of pain catastrophising determines if patients with long-standing subacromial impingement benefit from more resistance exercise: predefined secondary analyses from a pragmatic randomised controlled trial (the SExSI Trial).

OBJECTIVE: The primary aim was to investigate the effectiveness of adding more resistance exercise to usual care on pain mechanisms (including temporal summation, conditioned pain modulation (CPM) and local pain sensitivity) and pain catastrophising in people with subacromial impingement at 16 weeks follow-up. Second, to investigate the modifying effect of pain mechanisms and pain catastrophising on the interventions' effectiveness in improving shoulder strength and disability METHODS: 200 consecutive patients were randomly allocated to usual exercise-based care or the same plus additional elastic band exercise to increase total exercise dose. Completed add-on exercise dose was captured using an elastic band sensor. Outcome measures recorded at baseline, 5 weeks, 10 weeks and 16 (primary end point) weeks included temporal summation of pain (TSP) and CPM assessed at the lower leg, pressure pain threshold at the deltoid muscle (PPT-deltoid), pain catastrophising and the Shoulder Pain and Disability Index. RESULTS: Additional elastic band exercise was not superior to usual exercise-based care in improving pain mechanisms (TSP, CPM and PPT-deltoid) or pain catastrophising after 16 weeks. Interaction analyses showed that pain catastrophising (median split) modified the effectiveness of additional exercises (effect size 14 points, 95% CI 2 to 25), with superior results in the additional exercise group compared with the usual care group in patients with less pain catastrophising. CONCLUSION: Additional resistance exercise added to usual care was not superior to usual care alone in improving pain mechanisms or pain catastrophising. Additional exercise was, however, superior in improving self-reported disability in patients with lower levels of pain catastrophising at baseline. TRIAL REGISTRATION NUMBER: NCT02747251.

Prolonged slumped sitting causes neck pain and increased axioscapular muscle activity during a computer task in healthy participants - A randomized crossover study.

INTRODUCTION: Sitting posture may contribute to spinal pain. Effects of postures on pain, sensitivity and muscle activity during computer tasks were investigated. METHODS: Twenty-five healthy participants, seated at a workstation without backrest, completed four, 15-min typing tasks: A)Upright with forearm-support; B)Upright without forearm-support; C)Slumped with forearm-support; D)Slumped without forearm-support. Participants rated pain every minute on a numerical rating scale (NRS). RMS-EMG was recorded from upper/lower trapezius (UT, LT), serratus anterior and anterior/middle deltoid. At baseline and after tasks, pressure pain thresholds (PPTs) were recorded bilaterally over the head, UT, and leg. RESULTS: All tasks caused clinically relevant increased NRS (≥2/10) compared to baseline (P < 0.001). NRS was higher in Task-D (P < 0.003) and lower in Task-B (P < 0.005) than others. PPTs did not change from baseline. Task-D caused higher UT and LT RMS-EMG (P < 0.02) than other tasks. CONCLUSION: A 15-min task caused pain irrespective of posture with some causing larger changes than others.

Pain-related cognitions and emotional distress are not associated with conditioned pain modulation: an explorative analysis of 1142 participants with acute, subacute, and chronic pain.

ABSTRACT: Reduced conditioned pain modulation (CPM) and psychological distress co-occur frequently in many pain conditions. This study explored whether common negative pain cognitions and emotional factors were related to lower CPM in individuals across the spectrum from acute to chronic pain. Previously collected data on the CPM effect, pain-related cognitions (fear of movement, pain catastrophizing), and emotional distress (depression, anxiety) through questionnaires from 1142 individuals with acute, subacute, or chronic pain were used. The presence of negative psychological factors was dichotomized according to cutoff values for questionnaires. Associations between the presence of each negative psychological factor and the amplitude of pain reduction in the CPM paradigm was explored with Generalized Linear Models adjusted for sex, age, body mass index, and pain duration. A secondary analysis explored the cumulative effect of psychological factors on CPM. When dichotomized according to cutoff scores, 20% of participants were classified with anxiety, 19% with depression, 36% with pain catastrophizing, and 48% with fear of movement. The presence of any negative psychological factor or the cumulative sum of negative psychological factors was associated with lower CPM (individual factor: ß between -0.15 and 0.11, P ≥ 0.08; total: ß between -0.27 and -0.12, P ≥ 0.06). Despite the common observation of psychological factors and reduced CPM in musculoskeletal pain, these data challenge the assumption of a linear relationship between these variables across individuals with acute, subacute, and chronic pain. Arguably, there was a nonsignificant tendency for associations in nonexpected directions, which should be studied in a more homogenous population.

A novel computational approach to pain perception modelling within a Bayesian framework using quantitative sensory testing.

Pain perception can be studied as an inferential process in which prior information influences the perception of nociceptive input. To date, there are no suitable psychophysical paradigms to measure this at an individual level. We developed a quantitative sensory testing paradigm allowing for quantification of the influence of prior expectations versus current nociceptive input during perception. Using a Pavlovian-learning task, we investigated the influence of prior expectations on the belief about the varying strength of association between a painful electrical cutaneous stimulus and a visual cue in healthy subjects (N = 70). The belief in cue-pain associations was examined with computational modelling using a Hierarchical Gaussian Filter (HGF). Prior weighting estimates in the HGF model were compared with the established measures of conditioned pain modulation (CPM) and temporal summation of pain (TSP) assessed by cuff algometry. Subsequent HGF-modelling and estimation of the influence of prior beliefs on perception showed that 70% of subjects had a higher reliance on nociceptive input during perception of acute pain stimuli, whereas 30% showed a stronger weighting of prior expectations over sensory evidence. There was no association between prior weighting estimates and CPM or TSP. The data demonstrates relevant individual differences in prior weighting and suggests an importance of top-down cognitive processes on pain perception. Our new psychophysical testing paradigm provides a method to identify individuals with traits suggesting greater reliance on prior expectations in pain perception, which may be a risk factor for developing chronic pain and may be differentially responsive to learning-based interventions.