Identifying pain profiles in employees including work-related factors and pain perceptions: a cross-sectional study in Belgian companies.

OBJECTIVES: Studies usually investigate a limited number or a predefined combinations of risk factors for sickness absence in employees with pain. We examined frequently occurring combinations across a wide range of work-related factors and pain perceptions. DESIGN: Cross-sectional study. SETTING: Belgian companies that are under supervision of IDEWE, an external service for prevention and protection at work. PARTICIPANTS: In total, 249 employees experiencing pain for at least 6 weeks were included and filled out an online survey. OUTCOMES: Latent profile analysis was used to differentiate profiles of work-related factors (physical demands, workload, social support and autonomy) and pain perceptions (catastrophising, fear-avoidance beliefs and pain acceptance). Subsequently, profiles were compared on sociodemographics (age, gender, level of education, work arrangement, duration of complaints, multisite pain and sickness absence in the previous year) and predictors of sickness absence (behavioural intention and perceived behavioural control). RESULTS: Four profiles were identified. Profile 1 (38.2%) had favourable scores and profile 4 (14.9%) unfavourable scores across all indicators. Profile 2 (33.3%) had relatively high physical demands, moderate autonomy levels and favourable scores on the other indicators. Profile 3 (13.7%) showed relatively low physical demands, moderate autonomy levels, but unfavourable scores on the other indicators. Predictors of profiles were age (OR 0.93 and 95% CI (0.89 to 0.98)), level of education (OR 0.28 and 95% CI (0.1 to 0.79)) and duration of sickness absence in the previous year (OR 2.29 and 95% CI (0.89 to 5.88)). Significant differences were observed in behavioural intention (χ2=8.92, p=0.030) and perceived behavioural control (χ2=12.37, p=0.006) across the four profiles. CONCLUSION: This study highlights the significance of considering the interplay between work-related factors and pain perceptions in employees. Unfavourable scores on a single work factor might not translate into maladaptive pain perceptions or subsequent sickness absence, if mitigating factors are in place. Special attention must be devoted to employees dealing with unfavourable working conditions along with maladaptive pain perceptions. In this context, social support emerges as an important factor influencing sickness absence.

Posttraumatic headache: pain related evoked potentials (PREP) and conditioned pain modulation (CPM) to assess the pain modulatory function.

Posttraumatic headache (PTH) is common following traumatic brain injury and impacts quality of life. We investigated descending pain modulation as one possible mechanism for PTH and correlated it to clinical measures. Pain-related evoked potentials (PREP) were recorded in 26 PTH-patients and 20 controls after electrical stimulation at the right hand and forehead with concentric surface electrodes. Conditioned pain modulation (CPM) was assessed using painful cutaneous electric stimulation (PCES) on the right hand as test stimulus and immersion of the left hand into 10 °C-cold water bath as conditioning stimulus based on changes in pain intensity and in amplitudes of PCES-evoked potentials. All participants completed questionnaires assessing depression, anxiety, and pain catastrophising. PTH-patients reported significantly higher pain ratings during PREP-recording in both areas despite similar stimulus intensity at pain threshold. N1P1-amplitudes during PREP and CPM-assessment were lower in patients in both areas, but statistically significant only on the hand. Both, PREP-N1-latencies and CPM-effects (based on the N1P1-amplitudes and pain ratings) were similar in both groups. Patients showed significantly higher ratings for anxiety and depression, which did not correlate with the CPM-effect. Our results indicate generalized hyperalgesia for electrical stimuli in both hand and face in PTH. The lacking correlation between pain ratings and EEG parameters indicates different mechanisms of pain perception and nociception.

Unpacking the relationship between Big Five personality traits and experimental pain: A systematic review and meta-analysis.

Pain is essential for survival, but individual responses to painful stimuli vary, representing a complex interplay between sensory, cognitive, and affective factors. Individual differences in personality traits and in pain perception covary but it is unclear which traits play the most significant role in understanding the pain experience and whether this depends on pain modality. A systematic search identified 1534 records (CINAHL, MEDLINE, PsycInfo, PubMed and Web of Science), of which 22 were retained and included in a systematic review. Only studies from the pressure pain domain (n=6) could be compared in a formal meta-analysis to evaluate the relationship between Big Five traits and experimental pain. Pressure pain tolerance correlated positively with Extraversion and negatively with Neuroticism with a trivial effect size (<0.1). While these findings suggest personality might be only weakly related to pain in healthy individuals, we emphasize the need to consider standardization, biases, and adequate sample sizes in future research, as well as additional factors that might affect experimental pain sensitivity.

Reliability and minimal detectable change of dynamic temporal summation and conditioned pain modulation using a single experimental paradigm.

BACKGROUND: Quantitative sensory tests (QST) are frequently used to explore alterations in somatosensory systems. Static and dynamic QST like pain threshold and temporal summation (TS) and conditioned pain modulation (CPM) are commonly used to evaluate excitatory and inhibitory mechanisms involved in pain processing. The aim of the present study was to document the reliability and the minimal detectable change (MDC) of these dynamic QST measurements using a standardized experimental paradigm. MATERIAL AND METHODS: Forty-six (46) pain-free participants took part in 2 identical sessions to collect TS and CPM outcomes. Mechanical (pressure pain threshold [PPT]) and thermal (constant 2-minute heat pain stimulation [HPS]) nociceptive stimuli were applied as test stimuli, before and after a cold-water bath (conditioning stimulus). TS was interpreted as the change in pain perception scores during HPS. CPM were determined by calculating the difference in pain perception between pre- and post- water bath for both PPT and HPS. Relative and absolute reliability were analyzed with intra-class correlation coefficient (ICC2, k), standard error of the measurements (SEMeas) and MDC. RESULTS: Results revealed a good to excellent relative reliability for static QST (ICC ≥ 0.73). For TS, a poor to moderate relative reliability depending on the calculation methods (ICC = 0.25 ≤ ICC ≤ 0.59), and a poor relative reliability for CPM (ICC = 0.16 ≤ ICC ≤ 0.37), both when measured with mechanical stimulation (PPT) and thermal stimulation (HPS). Absolute reliability varied from 0.73 to 7.74 for static QST, 11 to 22 points for TS and corresponded to 11.42 points and 1.56 points for thermal and mechanical-induced CPM, respectively. MDC analyses revealed that a change of 1.58 to 21.46 point for static QST, 31 to 52 points for TS and 4 to 31 points for CPM is necessary to be interpreted as a real change. CONCLUSION: Our approach seems well-suited to clinical use. Although our method shows equivalent relative and absolute reliability compared to other protocols, we found that the reliability of endogenous pain modulation mechanisms is vulnerable, probably due to its dynamic nature.

Effect of exercise and manual therapy or kinesiotaping on sEMG and pain perception in chronic low back pain: a randomized trial.

The importance of incorporating lumbo-pelvic stability core and controlling motor exercises in patients with chronic low back pain (CLBP) reinforces the use of strategies to improve biopsychosocial beliefs by reducing biomedical postulations. However, clinical practice guidelines recommend multimodal approaches incorporating exercise and manual therapy (MT), and instead reject the application of kinesiotape (KT) in isolation. Therefore, the objectives of this study were to analyze the effects of 12 weeks of exercises combined with MT or KT on perceived low back pain using the visual analog scale (VAS) and muscle electric activity measured with electromyography (EMG) of the rectus abdominis and multifidus in CLBP (mild disability) and to explore the relationship between the rectus abdominis and multifidus ratios and pain perception after intervention. A blinded, 12-week randomized controlled trial (RCT) was carried out, involving three parallel groups of patients with CLBP. The study was registered at Clinicaltrial.gov and assigned the identification number NCT05544890 (19/09/22). The trial underwent an intention-to-treat analysis. The primary outcome revealed a multimodal treatment program supplemented by additional therapies such as MT and KT, resulting in significant reductions in perceived low back pain. The subjective assessment of individuals with CLBP indicated no discernible distinction between exclusive core stability exercises and control-motor training when combined with MT or KT. Notably, our findings demonstrated positive alterations in both the mean and peak EMG values of the right rectus abdominis in the exercise group, suggesting a beneficial impact on muscle activation. This study focused on assessing the activation levels of the trunk musculature, specifically the rectus abdominis (RA) and multifidus (MF), in individuals with CLBP exhibiting mild disability according to the Oswestry Disability Index. Importantly, improvements in the VAS values were observed independently of changes in muscle electrical activity.

Statistical learning shapes pain perception and prediction independently of external cues.

The placebo and nocebo effects highlight the importance of expectations in modulating pain perception, but in everyday life we don't need an external source of information to form expectations about pain. The brain can learn to predict pain in a more fundamental way, simply by experiencing fluctuating, non-random streams of noxious inputs, and extracting their temporal regularities. This process is called statistical learning. Here, we address a key open question: does statistical learning modulate pain perception? We asked 27 participants to both rate and predict pain intensity levels in sequences of fluctuating heat pain. Using a computational approach, we show that probabilistic expectations and confidence were used to weigh pain perception and prediction. As such, this study goes beyond well-established conditioning paradigms associating non-pain cues with pain outcomes, and shows that statistical learning itself shapes pain experience. This finding opens a new path of research into the brain mechanisms of pain regulation, with relevance to chronic pain where it may be dysfunctional.

Kynurenine Pathway Dysregulation and Pain Perception in Acute Pancreatitis: Has the Connection Unraveled?

AIM: Tryptophan (TRP), an essential amino acid, undergoes catabolism through various pathways. Notably, the kynurenine pathway (KP), constituting one of these pathways, exhibits a unidirectional impact on immune response and energy metabolism. Nonetheless, its influence on pain sensation is characterized by biphasic dynamics. This study aims to scrutinize the influence of the KP pathway on pain sensation, particularly within the context of pancreatic inflammation. METHODS: Our prospective case-control study involved individuals diagnosed with acute pancreatitis and a control group matched for gender and age. The patient cohort was subsequently subdivided into severe and non-severe subgroups. To assess metabolites within KP, two blood samples were collected from the patient cohort, one at the time of diagnosis and another during the recovery phase. Furthermore, for pain quantification, daily pain scores utilizing the Visual Analog Scale (VAS) were extracted from the patients' medical records. RESULTS: The study incorporated 30 patients along with an equivalent number of controls. A noticeable distinction was evident between the patient and control groups, characterized by an increase in kynurenine levels and a decrease in the tryptophan/kynurenine ratio. Throughout the process of disease recovery, a uniform decrease was observed in all KP metabolites, excluding 3-Hydroxykynurenine. Elevated levels of Kynurenic acid (KYNA) were correlated with increased pain scores. Critically, no apparent distinctions in KP metabolites were discerned concerning pain severity in patients with comorbidities characterized by neural involvement. CONCLUSION: Based on our results, the kynurenine pathway (KP) is activated in instances of acute pancreatitis. Elevated levels of KYNA were found to be associated with heightened pain scores. The operative stages within the KP responsible for pain modulation are impaired in cases characterized by neuropathy-induced pain sensation.

Data-driven dynamic profiles of tonic heat pain perception in pain-free volunteers are associated with differences in anandamide levels.

Our laboratory previously developed a method for assessing experimentally induced pain perception through a 2-min constant heat pain stimulation. However, the traditional analysis relying on group means struggles to interpret the considerable inter-individual variability due to the dynamic nature of the response. Recently, trajectory analysis techniques based on extended mixed models have emerged, providing insights into distinct response profiles. Notably, these methods have never been applied to pain paradigms before. Furthermore, various socio-demographic and neurobiological factors, including endocannabinoids, may account for these inter-individual differences. This study aims to apply the novel analysis to dynamic pain responses and investigate variations in response profiles concerning socio-demographic, psychological, and blood endocannabinoid concentrations. 346 pain-free participants were enrolled in a psychophysical test involving a continuous painful heat stimulation lasting for 2 min at a moderate intensity. Pain perception was continuously recorded using a computerized visual scale. Dynamic pain response analyses were conducted using the innovative extended mixed model approach. In contrast to the traditional group-mean analysis, the extended mixed model revealed three pain response trajectories. Trajectory 1 is characterized by a delay peak pain. Trajectory 2 is equivalent to the classic approach (peak pain follow by a constant and moderate increase of pain perception). Trajectory 3 is characterized by extreme responses (steep peak pain, decrease, and increase of pain perception), Furthermore, age and blood anandamide levels exhibited significant variations among these three trajectories. Using an innovative statistical approach, we found that a large proportion of our sample had a response significantly different from the average expected response. Endocannabinoid system seems to play a role in pain response profile.

Perioperative pain perception in patients undergoing dermatologic surgery with local anesthesia - A prospective observational study.

BACKGROUND: Dermatosurgical procedures are predominantly performed under local anesthesia, yet there are few studies on perioperative pain management for extensive or staged procedures under local anesthesia. The purpose of this study was to assess pain during dermatologic surgery, describe perioperative pain management, and identify factors that influence pain perception. PATIENTS AND METHODS: This prospective, monocentric study included inpatients undergoing dermatologic surgery under local anesthesia from April to December 2021. Preoperative demographic data, a pain questionnaire, and four psychometric questionnaires (PCS, LOT-R, SFQ, PHQ-9) were collected. Postoperative pain and analgesic use during the first 24 hours were recorded. RESULTS: A total of 120 patients (with a total of 191 interventions) were included in the study. Mean postoperative pain was reported to be very low (NRS < 2). Preoperative pain and expected postoperative pain were found to be predictive of postoperative pain. There was a strong correlation between catastrophizing and preoperative anxiety (r = 0.65) and a moderate correlation between depression and preoperative anxiety (r = 0.46). CONCLUSIONS: Dermatologic surgery under local anesthesia is generally considered painless. During preoperative counseling and assessment, attention should be paid to patients who fear surgery, report pain, or anticipate postoperative pain, as they have an increased risk of experiencing postoperative pain.

A comparative evaluation of the efficiency of warm local anesthetic solution delivered on precooled injection sites with the conventional local anesthetic technique in 7-9-year-old children: A randomized split-mouth cross-over trial.

BACKGROUND: Both precooling the site and injecting a warm anesthetic solution have proven to be efficient in reducing pain individually. However, there is insufficient data on evaluating the efficiency of precooling the site of injection along with the simultaneous administration of a warm local anesthetic solution on the same site in a single patient. AIM: The aim of this study was to evaluate and compare the efficacy, pain perception, hemodynamic changes, and adverse effects of a warm local anesthetic solution injected on precooled injection sites using 2% lignocaine with the conventional local anesthetic technique during inferior alveolar nerve block in 7-9-year-old children. METHODS: A split-mouth, double-blinded, randomized clinical trial was conducted on 70 children who received 2% lignocaine with either technique A or B during the first or second appointment of the treatment procedure. The pain perception, anesthetic efficacy, pulse rate, oxygen saturation levels, and adverse events were evaluated. RESULTS: Pain during injection and treatment after administration of the warm local anesthesia (LA) technique was less as compared to the conventional block technique. Anesthetic success was observed with a faster onset of action (212.57 ± 32.51 s) and shorter duration of LA (165.16 ± 33.09 min) in the warm local technique as compared to the conventional technique. No significant differences were found with regard to heart rate and oxygen saturation levels between the two techniques. Administrating warm LA solutions at precooled injection sites revealed fewer adverse events. CONCLUSION: Injecting warm LA solution on precooled injection sites causes less discomfort and anxiety in children, which makes it more suitable for the child as well as the pediatric dentist.

Inferior alveolar nerve block anesthesia in children: The effect of ibuprofen and phentolamine mesylate on pain perception.

CONTEXT: For successfully managing pediatric dental patients, local anesthesia is essential to eliminate pain during or after the operative period. An early recovery from soft-tissue anesthesia after an inferior alveolar nerve block (IANB) should benefit a young child patient by avoiding the risk of inadvertently biting the soft tissues. AIMS: Hence, the purpose of the study was to (1) evaluate and compare the efficacy of pre- and postoperative ibuprofen on pain perception in children who undergo IANB anesthesia with or without the use of PM and (2) evaluate the average time required for reversal of anesthesia symptoms using phentolamine mesylate. METHODS: The present study was a randomized, clinical trial performed among 60 children between 6 and 8 years of age using a convenient sampling method. The children were randomly assigned into four equal groups of 15 each using the computer-generated randomization sequence. IANB anesthesia was performed using 2% lignocaine with 1:100,000 epinephrine, and a mandibular primary molar pulpotomy was performed on each group. Group 1: the ibuprofen tablet was taken 1 h before the onset of the procedure. Group 2: ibuprofen tablet 30 min after the pulpotomy procedure. Group 3: the ibuprofen tablet was taken 1 h before the onset of the procedure, and the Phentolamine mesylate (PM) injection was administered. Group 4: immediately after the pulpotomy, the PM injection was administered, and an ibuprofen tablet was taken 30 min after the pulpotomy procedure. All children were assessed for the duration of soft-tissue anesthesia, their behavior scores and pain rating, as well as the incidence of postoperative self-inflicted injuries. STATISTICAL ANALYSIS USED: A one-way ANOVA was used to compare the average time needed for the reversal of anesthetic symptoms between groups. The effects of phentolamine, local anesthetics, and ibuprofen on the child's behavior and pain scores were compared using the Student's t-test. For the study, P < 0.05 was accepted as statistically significant. RESULTS: The time needed for the full reversal of anesthetic symptoms to manifest on the tongue and lip was substantially reduced by the injection of phentolamine (P < 0.001). The use of phentolamine for reversal or the intake of ibuprofen pre- or postoperatively did not exhibit any significant variation in the behavior, pain experience, or incidence of self-inflicted injuries in the child. CONCLUSION: It is evident that although phentolamine injections shorten the duration of anesthesia, the adjunctive use of pre- or postoperative ibuprofen did not significantly alter pain scores.

The independence and predictivity of resting pain-free slow alpha frequency as a biomarker of pain: A reply to Mazaheri et al.

In response to Mazaheri et al.'s critique, we revisited our study (Valentini et al., 2022) on the relationship between peak alpha frequency (PAF) and pain. Their commentary prompted us to reassess our data to address the independence between slow and slowing alpha brain oscillations, as well as the predictivity of slow alpha oscillations in pain perception. Bayesian correlation analyses revealed mixed support for independence. Investigating predictivity, we found inconsistent associations between pre-PAF and unpleasantness ratings. We critically reflected on methodological and theoretical issues on the path to PAF validation as a pain biomarker. We emphasized the need for diversified methodology and analytical approaches as well as robust findings across research groups.

Intracranial EEG signals disentangle multi-areal neural dynamics of vicarious pain perception.

Empathy enables understanding and sharing of others' feelings. Human neuroimaging studies have identified critical brain regions supporting empathy for pain, including the anterior insula (AI), anterior cingulate (ACC), amygdala, and inferior frontal gyrus (IFG). However, to date, the precise spatio-temporal profiles of empathic neural responses and inter-regional communications remain elusive. Here, using intracranial electroencephalography, we investigated electrophysiological signatures of vicarious pain perception. Others' pain perception induced early increases in high-gamma activity in IFG, beta power increases in ACC, but decreased beta power in AI and amygdala. Vicarious pain perception also altered the beta-band-coordinated coupling between ACC, AI, and amygdala, as well as increased modulation of IFG high-gamma amplitudes by beta phases of amygdala/AI/ACC. We identified a necessary combination of neural features for decoding vicarious pain perception. These spatio-temporally specific regional activities and inter-regional interactions within the empathy network suggest a neurodynamic model of human pain empathy.

Pain perception as hierarchical Bayesian inference: A test case for the theory of constructed emotion.

An intriguing perspective about human emotion, the theory of constructed emotion considers emotions as generative models according to the Bayesian brain hypothesis. This theory brings fresh insight to existing findings, but its complexity renders it challenging to test experimentally. We argue that laboratory studies of pain could support the theory because although some may not consider pain to be a genuine emotion, the theory must at minimum be able to explain pain perception and its dysfunction in pathology. We review emerging evidence that bear on this question. We cover behavioral and neural laboratory findings, computational models, placebo hyperalgesia, and chronic pain. We conclude that there is substantial evidence for a predictive processing account of painful experience, paving the way for a better understanding of neuronal and computational mechanisms of other emotions.

Donor site wound healing following free gingival graft surgery using platelet rich fibrin: A randomized controlled trial.

BACKGROUND: The primary purpose of this two-arm, parallel design, randomized controlled study is to compare healing of the palatal tissue donor site when platelet-rich fibrin (PRF) is used as a wound dressing compared to the use of a hemostatic agent. Secondary outcomes of patient pain perception and analgesic intake were also evaluated. METHODS: Seventy-four patients receiving free gingival grafts were randomized to receive either PRF (test) or hemostatic agent (control) as a palatal wound dressing by patients selecting a sealed envelope containing their group assignment (initially 37 envelopes for PRF group and 37 for hemostatic agent group). Patient pain assessment and analgesic consumption were documented using a 21-point numerical scale (NMRS-21) at 24, 48, and 72 hours post-surgery. At 1-, 2-, 3-, and 4-week follow-up appointments palatal early healing index (PEHI) scores including wound color, epithelialization, presence or absence of swelling, granulation tissue, and bleeding on gentle palpation were generated by direct intraoral examination by a blinded examiner unaware of the patients' treatment group. RESULTS: NMRS-21 pain scores showed a significant reduction in pain over time in both groups, with no significant difference between groups at any time point. No significant between-group difference was found in the amount of analgesics taken by patients at 24, 48, and 72 hours. There was significant improvement in PEHI scores over the 4-week time period in both groups, but there was no significant difference in PEHI score at each time point (1, 2, 3, 4 weeks) between groups.  CONCLUSIONS: Study findings suggest that there is no difference in early palatal wound healing, patient pain perception, or analgesic consumption between use of PRF or a hemostatic agent as donor-site wound dressings.

Dissecting shared pain representations to understand their behavioral and clinical relevance.

Accounts of shared representations posit that the experience of pain and pain empathy rely on similar neural mechanisms. Experimental research employing novel analytical and methodological approaches has made significant advances in both the identification and targeted manipulation of such shared experiences and their neural underpinnings. This revealed that painful experiences can be shared on different representational levels, from pain-specific to domain-general features, such as negative affect and its regulation. In view of direct links between such representations and social behaviors such as prosocial behavior, conditions characterized by aberrant pain processing may come along with heavy impairments in the social domain, depending on the affected representational level. This has wide potential implications in light of the high prevalence of pain-related clinical conditions, their management, and the overuse of pain medication. In this review and opinion paper, we aim to chart the path toward a better understanding of the link between shared affect and prosocial behavior.

An evaluation of the behavioural inhibition system and behavioural activation system (BIS-BAS) model of pain in athletes.

This study examined coping and pain responses using a behavioural inhibition (BIS) - behavioural activation (BAS) framework in 489 student athletes (M(age) = 20, SD = 4; 69% female). Two samples of athletes (226 pain-free athletes and 232 athletes with current pain) completed surveys assessing BIS- and BAS-related cognitions, emotions, and behaviours. Distinct groupings of BAS-related variables were identified in both samples, evidenced by significant positive correlations within BAS-related variables (positive affect, pain openness, approach thoughts and behaviours). Most BIS-related variables (depression, anxiety, harm beliefs, pain catastrophizing and avoidance behaviours) were also correlated in the sample of athletes with pain; however, this was not observed in pain-free athletes. In athletes with pain, BIS-related variables were significantly associated with pain variables, with this association stronger than that found for BAS-related variables. Regression analyses highlighted the pivotal role of pain catastrophizing as a predictor of pain unpleasantness and intensity. Findings shed light on the factors shaping athletes' coping, pain perception and decisions as to whether to pause or push through. Future investigations to explore these dynamics in more depth may aid in the development of targeted interventions that enhance athletes' ability to cope and to manage pain more effectively.

Chronic pain - A maladaptive compensation to unbalanced hierarchical predictive processing.

The ability to perceive pain presents an interesting evolutionary advantage to adapt to an ever-changing environment. However, in the case of chronic pain (CP), pain perception hinders the capacity of the system to adapt to changing sensory environments. Similar to other chronic perceptual disorders, CP is also proposed to be a maladaptive compensation to aberrant sensory predictive processing. The local-global oddball paradigm relies on learning hierarchical rules and processing environmental irregularities at a local and global level. Prediction errors (PE) between actual and predicted input typically trigger an update of the forward model to limit the probability of encountering future PEs. It has been hypothesised that CP hinders forward model updating, reflected in increased local deviance and decreased global deviance. In the present study, we used the local-global paradigm to examine how CP influences hierarchical learning relative to healthy controls. As hypothesised, we observed that deviance in the stimulus characteristics evoked heightened local deviance and decreased global deviance of the stimulus-driven PE. This is also accompanied by respective changes in theta phase locking that is correlated with the subjective pain perception. Changes in the global deviant in the stimulus-driven-PE could also be explained by dampened attention-related responses. Changing the context of the auditory stimulus did not however show a difference in the context-driven PE. These findings suggest that CP is accompanied by maladaptive forward model updating where the constant presence of pain perception disrupts local deviance in non-nociceptive domains. Furthermore, we hypothesise that the auditory-processing based biomarker identified here could be a marker of domain-general dysfunction that could be confirmed by future research.