An afferent nerve-like electronic device with somatic mechanical perception and sensation management.

Tactile and pain perception are essential for biological skin to interact with the external environment. This complex interplay of sensations allows for the detection of potential threats and appropriate responses to stimuli. However, the challenge is to enable flexible electronics to respond to mechanical stimuli such as biological skin, and researchers have not clearly reported the successful integration of somatic mechanical perception and sensation management functions into neuro-like electronics. In this work, an afferent nerve-like device with a pressure sensor and a perception management module is proposed. The pressure sensor comprises two conductive fabric layers and an ionic hydrogel, forming a capacitor structure that emulates the swift transition from tactile to pain perception under mechanical stimulation. Drawing inspiration from the neuronal "gate control" mechanism, the sensation management module adjusts signals in response to rubbing, accelerating the discharge process and reducing the perception duration, thereby replicating the inhibitory effect of biological neurons on pain following tactile interference. This integrated device, encompassing somatic mechanical perception and sensation management, holds promise for applications in soft robotics, prosthetics, and human-machine interaction.

Substance P concentration is associated with the inflammatory response and pain perception in patients with chronic pain in peripheral artery disease.

<b>Introduction:</b> Previous studies indicate a significant role of the inflammatory response in the etiopathogenesis of peripheral artery disease (PAD) and chronic pain (CP).<b>Aim:</b> The aim of the study was to determine the relationship between the concentration of SP and the level/concentration of inflammatory mediators (pro-inflammatory cytokines, positive and negative acute phase protein, anti-inflammatory cytokines) and pain intensity in people suffering from chronic pain (CP) in the course of PAD.<b>Material and methods:</b> We examined 187 patients of the Department of Vascular Surgery. As many as 92 patients with PAD and CP (study group) were compared to 95 patients with PAD without CP (control group). The relationship between SP and the level/concentration of fibrinogen, C-reactive protein (CRP), antithrombin III (AT), serum albumin, interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-α) and pain intensity (Numeric Rating Scale; NRS) was analyzed. Statistical analysis was performed using the R program, assuming the level of statistical significance of α = 0.05.<b>Results:</b> Patients with CP had significantly higher levels of fibrinogen (P < 0.001), CRP (P < 0.001), SP (P < 0.001), IL-10 (P < 0.001), and lower serum albumin levels (P < 0.023). Higher SP concentration was associated with higher levels of IL-10, CRP, and pain intensity. In both groups, SP concentration correlated negatively with the level of fibrinogen (P < 0.001) as well as with albumin in the control group (P < 0.001).<b>Conclusions:</b> Thus, there is a relationship between the concentration of SP and fibrinogen, along with CRP, IL-10, and the intensity of pain in people suffering from CP in the course of PAD, and the level of albumin in the group without CP.

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.

Astrocytes in Pain Perception: A Systems Neuroscience Approach.

Astrocytes play an active role in the function of the brain integrating neuronal activity and regulating back neuronal dynamic. They have recently emerged as active contributors of brain's emergent properties such as perceptions. Here, we analyzed the role of astrocytes in pain perception from the lens of systems neuroscience, and we do this by analyzing how astrocytes encode nociceptive information within brain processing areas and how they are key regulators of the internal state that determines pain perception. Specifically, we discuss the dynamic interactions between astrocytes and neuromodulators, such as noradrenaline, highlighting their role in shaping the level of activation of the neuronal ensemble, thereby influencing the experience of pain. Also, we will discuss the possible implications of an "Astro-NeuroMatrix" in the integration of pain across sensory, affective, and cognitive dimensions of pain perception.

Effects of hippocampal damage on pain perception in a rat model of Alzheimer's disease induced by amyloid-ß and ibotenic acid injection into the hippocampus.

Patients with Alzheimer's disease (AD) present with a variety of symptoms, including core symptoms as well as behavioral and psychological symptoms. Somatosensory neural systems are generally believed to be relatively unaffected by AD until late in the course of the disease; however, somatosensory perception in patients with AD is not yet well understood. One factor that may complicate the assessment of somatosensory perception in humans centers on individual variations in pathological and psychological backgrounds. It is therefore necessary to evaluate somatosensory perception using animal models with uniform status. In the current study, we focused on the hippocampus, the primary site of AD. We first constructed a rat model of AD model using bilateral hippocampal injections of amyloid-ß peptide 1-40 and ibotenic acid; sham rats received saline injections. The Morris water maze test was used to evaluate memory impairment, and the formalin test (1 % or 4 % formalin) and upper lip von Frey test were performed to compare pain perception between AD model and sham rats. Finally, histological and immunohistochemical methods were used to evaluate tissue damage and neuronal activity, respectively, in the hippocampus. AD model rats showed bilateral hippocampal damage and had memory impairment in the Morris water maze test. Furthermore, AD model rats exhibited significantly less pain-related behavior in phase 2 (the last 50 min of the 60-minute observation) of the 4 % formalin test compared with the sham rats. However, no significant changes were observed in the von Frey test. Immunohistochemical observations of the trigeminal spinal subnucleus caudalis after 4 % formalin injection revealed significantly fewer c-Fos-immunoreactive cells in AD model rats than in sham rats, reflecting reduced neuronal activity. These results indicate that AD model rats with hippocampal damage have reduced responsiveness to persistent inflammatory chemical stimuli to the orofacial region.

Experimental nerve block study on painful withdrawal reflex responses in humans.

The nociceptive withdrawal reflex (NWR) is a protective limb withdrawal response triggered by painful stimuli, used to assess spinal nociceptive excitability. Conventionally, the NWR is understood as having two reflex responses: a short-latency Aß-mediated response, considered tactile, and a longer-latency Aδ-mediated response, considered nociceptive. However, nociceptors with conduction velocities similar to Aß tactile afferents have been identified in human skin. In this study, we investigated the effect of a preferential conduction block of Aß fibers on pain perception and NWR signaling evoked by intradermal electrical stimulation in healthy participants. We recorded a total of 198 NWR responses in the intact condition, and no dual reflex responses occurred within our latency bandwidth (50-150 ms). The current required to elicit the NWR was higher than the perceptual pain threshold, indicating that NWR did not occur before pain was felt. In the block condition, when the Aß-mediated tuning fork sensation was lost while Aδ-mediated nonpainful cooling was still detectable (albeit reduced), we observed that the reflex was abolished. Further, short-latency electrical pain intensity at pre-block thresholds was greatly reduced, with any residual pain sensation having a longer latency. Although electrical pain was unaffected at suprathreshold current, the reflex could not be evoked despite a two-fold increase in the pre-block current and a five-fold increase in the pre-block pulse duration. These observations lend support to the possible involvement of Aß-fiber inputs in pain and reflex signaling.

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.

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.

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.

Neural circuit basis of placebo pain relief.

Placebo effects are notable demonstrations of mind-body interactions1,2. During pain perception, in the absence of any treatment, an expectation of pain relief can reduce the experience of pain-a phenomenon known as placebo analgesia3-6. However, despite the strength of placebo effects and their impact on everyday human experience and the failure of clinical trials for new therapeutics7, the neural circuit basis of placebo effects has remained unclear. Here we show that analgesia from the expectation of pain relief is mediated by rostral anterior cingulate cortex (rACC) neurons that project to the pontine nucleus (rACC→Pn)-a precerebellar nucleus with no established function in pain. We created a behavioural assay that generates placebo-like anticipatory pain relief in mice. In vivo calcium imaging of neural activity and electrophysiological recordings in brain slices showed that expectations of pain relief boost the activity of rACC→Pn neurons and potentiate neurotransmission in this pathway. Transcriptomic studies of Pn neurons revealed an abundance of opioid receptors, further suggesting a role in pain modulation. Inhibition of the rACC→Pn pathway disrupted placebo analgesia and decreased pain thresholds, whereas activation elicited analgesia in the absence of placebo conditioning. Finally, Purkinje cells exhibited activity patterns resembling those of rACC→Pn neurons during pain-relief expectation, providing cellular-level evidence for a role of the cerebellum in cognitive pain modulation. These findings open the possibility of targeting this prefrontal cortico-ponto-cerebellar pathway with drugs or neurostimulation to treat pain.

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.

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.

Empathic pain: Exploring the multidimensional impacts of biological and social aspects in pain.

Empathic pain refers to an individual's perception, judgment, and emotional response to others' pain. This complex social cognitive ability is crucial for healthy interactions in human society. In recent years, with the development of multidisciplinary research in neuroscience, psychology and sociology, empathic pain has become a focal point of widespread attention in these fields. However, the neural mechanism underlying empathic pain remain a controversial and unresolved area. This review aims to comprehensively summarize the history, influencing factors, neural mechanisms and pharmacological interventions of empathic pain. We hope to provide a comprehensive scientific perspective on how humans perceive and respond to others' pain experiences and to provide guidance for future research directions and clinical applications. This article is part of the Special Issue on "Empathic Pain".

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.

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.