Effectiveness of Animal-Assisted Activity on Pain Perception and Anxiety of Children Undergoing Intraoral Local Anesthetic Administration.

Purpose: To investigate the impact of animal-assisted activity (AAA) involving a dog (play therapy) on reducing the pain experienced by children during the administration of local anesthetic (LA). Methods: Children between the ages of eight and 12 years who required LA administration were randomized into an AAA group and a control group. Baseline data for the simplified Modified Child Dental Anxiety Scale-Faces version (MCDAS[f]) was recorded, followed by the implementation of either AAA with standard care or standard care alone. The conventional protocol was followed for the administration of LA. Procedural pain was evaluated using both the Faces Pain Scale-Revised (FPS-R) and the Faces, Legs, Activity, Cry, and Consolability Scale (FLACC). All variations in pulse were also recorded. After the procedure, a simplified MCDAS(f) was recorded once again. The data were tabulated and statistically analyzed. Results: The children in the AAA group reported lower pain scores, as measured by FPS-R, compared to the control group (P =0.009). Pain, as observed in the FLACC scores, was also low in the experimental group (P <0.001). A notable reduction in anxiety scores (P <0.001) was observed among children assigned to the AAA group. Conclusion: AAA involving a dog led to a reduction in the pain experienced by children undergoing LA administration, subsequently decreasing anxiety.

Comparative evaluation of the effect of impregnated retraction cord versus laser on gingival attachment level and pain perception following retraction for subgingival margins - A prospective, split-mouth, controlled, clinical study.

AIM: To evaluate and compare the effect of impregnated retraction cord vs Laser on gingival attachment level and pain perception following retraction for subgingival margins. SETTINGS AND DESIGN: Many methods for achieving and measuring the amount of gingival retraction in fixed prosthodontic work have been advocated. Though the gingival attachment level is crucial in Periodontology, the literature available regarding the effect of these retraction methods on the same is scarce. Hence, this clinical study was designed to compare the pain perception and amount of gingival recession when impregnated cord and laser were used for retraction. MATERIALS AND METHODS: In 40 subjects (age range of 20 to 40 years) with single missing maxillary incisor, the abutments were prepared with subgingival margins, to receive a full coverage metal-ceramic fixed dental prosthesis. The gingiva was retracted on one of the abutments with impregnated retraction cord and on the other with diode laser. Gingival attachment levels were compared at six sites per abutment using superimposition of digital scans, preoperative and four weeks after cementation of final prosthesis. STATISTICAL ANALYSIS USED: Statistical analysis of the data for gingival recession was done using t-test. Pain perception was analysed with Chi-square test. Pain perception by patients following retraction was compared with VAS scale. RESULTS: The average values of gingival recession on buccal side were 0.61 mm and 0.38 mm and on the palatal side were 0.58 mm and 0.35 mm for impregnated retraction cord and laser respectively. The P values of <0.01 indicated a highly significant difference between the two groups. Intragroup comparison did not show significant differences between various sites. Pain and discomfort produced by cord method was moderate in comparison with mild/no pain with diode laser and the difference was highly significant.Conclusion: Retraction cord produced more gingival recession than the diode laser, which was statistically highly significant on both buccal and palatal aspects of the teeth. Patients experience with diode laser technique was less painful in comparison with retraction cord method.

Exercise induced hypoalgesia during different intensities of a dynamic resistance exercise: A randomized controlled trial.

INTRODUCTION: Exercise produces an immediate lessening of pain sensitivity (Exercise-Induced Hypoalgesia (EIH)) in healthy individuals at local and distant sites, possibly through a shared mechanism with conditioned pain modulation (CPM). Dynamic resistance exercise is a recommended type of exercise to reduce pain, yet limited research has examined the effects of intensity on EIH during this type of exercise. Therefore, the primary purpose of this study is to compare changes in PPT at a local and distant site during a leg extension exercise at a high intensity, a low intensity, or a quiet rest condition. A secondary purpose is to examine if CPM changes after each intervention. The final purpose is to examine if baseline pain sensitivity measures are correlated with response to each intervention. METHODS: In a randomized controlled trial of 60 healthy participants, participants completed baseline pain sensitivity testing (heat pain threshold, temporal summation, a cold pressor test as measure of CPM) and were randomly assigned to complete a knee extension exercise at: 1) high intensity (75% of a 1 Repetition Maximum (RM), 2) low intensity (30% 1RM), or 3) Quiet Rest. PPT was measured between each set at a local (quadriceps) and distant (trapezius) site during the intervention. CPM was then repeated after the intervention. To test the first purpose of the study, a three-way ANOVA examined for time x site x intervention interaction effects. To examine for changes in CPM by group, a mixed-model ANOVA was performed. Finally, a Pearson Correlation examined the association between baseline pain sensitivity and response to each intervention. RESULTS: Time x site x intervention interaction effects were not significant (F(5.3, 150.97) = 0.87, p = 0.51, partial eta2 = 0.03). CPM did not significantly change after the interventions (time x intervention F(1,38) = 0.81, p = 0.37, partial eta2 = 0.02. EIH effects at the quadriceps displayed a significant, positive moderate association with baseline HPT applied over the trapezius (r = 0.61, p<0.01) and TS (r = 0.46, p = 0.04). DISCUSSION: In healthy participants, PPT and CPM did not significantly differ after a leg extension exercise performed at a high intensity, low intensity, or quiet rest condition. It is possible pre-intervention CPM testing with a noxious stimuli may have impaired inhibitory effects frequently observed during exercise but future research would need to examine this hypothesis.

Skin conductance algesimeter is unreliable during sudden perioperative temperature increases.

OBJECTIVES: Pain assessment in anesthetized and non-communicative patients remains a challenge. Clinical signs such as tachycardia, hypertension, sweat and tears, have a low specificity for pain and should therefore ideally be replaced by more specific monitoring techniques. Skin conductance variability has been demonstrated to establish a patients' sensitivity to pain, but may be influenced by temperature changes that leads to profuse sweating. The aim of this pilot study was to test skin conductance changes during sudden temperature changes due to hyperthermic intraperitoneal chemotherapy (HIPEC) perfusation. METHODS: We investigated skin conductance algesimeter (SCA) in ten consecutive patients undergoing cytoreductive surgery and HIPEC. Results from the SCA was compared to other standard physiological variables at seven time points during the surgical procedure, in particular during the period with hyperthermic intraabdominal perfusion leading to an increase in the patients core temperature. RESULTS: Nine out of ten patients had an increase in the SCA measurements during the HIPEC phase correlating the increase in temperature. CONCLUSION: SCA is unreliable to detect increased pain sensation during sudden perioperative temperature changes in adult patients.

Investigating mortality salience as a potential causal influence and moderator of responses to laboratory pain.

Background: Because pain can have profound ramifications for quality of life and daily functioning, understanding nuances in the interplay of psychosocial experiences with pain perception is vital for effective pain management. In separate lines of research, pain resilience and mortality salience have emerged as potentially important psychological correlates of reduced pain severity and increased tolerance of pain. However, to date, there has been a paucity of research examining potentially interactive effects of these factors on pain perception. To address this gap, the present experiment investigated mortality salience as a causal influence on tolerance of laboratory pain and a moderator of associations between pain resilience and pain tolerance within a Chinese sample. Methods: Participants were healthy young Chinese adults (86 women, 84 men) who first completed a brief initial cold pressor test (CPT) followed by measures of demographics and pain resilience. Subsequently, participants randomly assigned to a mortality salience (MS) condition completed two open-ended essay questions in which they wrote about their death as well as a death anxiety scale while those randomly assigned to a control condition completed analogous tasks about watching television. Finally, all participants engaged in a delay task and a second CPT designed to measure post-manipulation pain tolerance and subjective pain intensity levels. Results: MS condition cohorts showed greater pain tolerance than controls on the post-manipulation CPT, though pain intensity levels did not differ between groups. Moderator analyses indicated that the relationship between the behavior perseverance facet of pain resilience and pain tolerance was significantly stronger among MS condition participants than controls. Conclusions: This experiment is the first to document potential causal effects of MS on pain tolerance and Ms as a moderator of the association between self-reported behavior perseverance and behavioral pain tolerance. Findings provide foundations for extensions within clinical pain samples.

Personalized analysis of pain-weather associations: a pilot study.

Background and purpose:

It is a wellknown belief that weather can influence human health, including pain sensation. However, the current data are controversial, which might be due to the wide range of interindividual differences. The present study aimed to characterize the individual pain–weather associations during chronic pain by utilizing several data analytical methods.

The study included 3-3 patients with (P1, P3, and P4) or without (P2, P5, P6) diabetes mellitus and signs of trigeminal neuralgia or low back pain. Subjective pain scores (0–10) and 12 weather parameters (terrestrial, geomagnetic, and solar) were recorded for one month repeated three times daily. Nonparametric Spearman’s correlation (Sp), multiple regression (Mx), and principal component (PCA) analyses were performed to evaluate associations between pain and meteorological factors obtained at the day of recorded pain value, 2 days before and 2 days after the recorded pain, and the changes in these parameters (5 × 12 parameters). Complex scores were calculated based on the results of these analyses.

While the temperature had the highest effects on the pain levels in most of the participants, huge interindividual dif­ferences in the degree and the direction of the associations between pain and weather parameters could be obtained. The analytic methods also revealed subjectspecific results, and the synthesis of different statistical methods as total scores provided a personalized map for each patient, which showed disparate patterns across the study participants. Thus, Participants 2 and 5 had higher scores for Mx compared to Sp; furthermore, certain factors showed opposite direction in their associations with the pain level depending on the type of analysis (Sp vs Mx). In contrast, P3 had a lower score for Mx compared to Sp, which might suggest a low level of weather sensitivity on the association between the different weather parameters in this subject. Furthermore, participants P4 and P6 had a very high level of weather sensitivity, while P1 had an opposite pattern. Regarding the time point-related effects on the pain level, most patients were sensitive to parameters obtained at the same day or two days before, except the P1 subject, who had the highest sensitivity to weather parameters detected two days after.

The present study highlights the importance of integrating different data analysis approaches to elucidate the individual connections between pain and most of the weather parameters. In conclusion, complex personalized profiling should be considered for the characterization of pain–weather associations by applying different data analytical approaches, which may provide feedback to physicians and patients. 

Structural alterations and pain perception at the ankle joint in patients with haemophilia.

BACKGROUND: Patients with haemophilia (PwH) suffer from chronic pain due to joint alterations induced by recurring haemorrhage. OBJECTIVES: This study aimed to investigate the relationship between structural alterations and pain perception at the ankle joint in PwH. PATIENTS/METHODS: Ankle joints of 79 PwH and 57 healthy controls (Con) underwent ultrasound examination (US) and assessment of pain sensitivity via pressure pain thresholds (PPT). US discriminated between joint activity (synovitis) and joint damage (cartilage and/or bone degeneration) applying the HEAD-US protocol. Based on US-findings, five subgroups were built: PwH with activity/damage, PwH with activity/no damage, PwH with no activity/no damage, controls with activity/no damage and controls with no activity/no damage. RESULTS: Joint activity and joint damage were significantly increased in ankles of PwH compared to Con (p ≤.001). Subgroup analysis revealed that structural alterations negatively impact pain perception. This is particularly evident when comparing PwH with both activity/damage to PwH with no activity/no damage at the tibiotalar joint (p = .001). At the fibulotalar joint, no significant differences were observed between PwH subgroups. Further analysis showed that both joint activity and joint damage result in an increase in pain sensitivity (p ≤.001). CONCLUSION: The data suggest a relation between joint activity, joint damage and pain perception in PwH. Even minor changes due to synovitis appear to affect pain perception, with the effect not intensifying at higher levels of inflammation. In terms of joint damage, severe degeneration leads to a sensitised pain state most robustly, whereas initial changes do not seem to significantly affect pain perception.

Reduced reactivity to fear conditioning and pain tests in persons involved in violent video gaming is influenced by adverse childhood experiences.

Video gaming, including violent video gaming, has become very common and lockdown measures of the COVID-19 pandemic even increased the prevalence rates. In this study, we examined if violent video gaming is associated with more adverse childhood experiences (ACE) and if it impairs pain processing and fear conditioning. We tested three groups of participants (violent video gamers, nonviolent video gamers, and non-gamers) and examined fear conditioning as well as pain perception during functional magnetic resonance imaging (fMRI). Violent video gamers displayed significantly higher pain thresholds as well as pain tolerance for electric stimulation, pressure pain stimulation, and cold pressor pain measurements than nonviolent video gamers and non-gamers. This relationship was moderated by adverse childhood experiences, especially physical neglect. Brain images acquired during the fear conditioning fMRI task showed that violent video gamers display significantly less differential brain activation to stimuli signaling pain versus no pain in the anterior cingulate cortex, the juxtapositional lobule cortex, and the paracingulate gyrus compared to non-gamers. There was also a significant negative correlation between adverse childhood experiences and activation in the precuneus and the intracalcarine cortex for signals of pain versus safety. The results of this study imply that violent video gaming is related to reduced processing of pain and signals of pain in a fear learning task, dependent of adverse childhood experiences. These mechanisms need to be examined in more detail and these data could be helpful in preventing the onset and adverse consequences of violent video gaming.

The effect of 6GHz radiofrequency electromagnetic radiation on rat pain perception.

This paper presents data on pain perception in rats exposed to 6 GHz radiofrequency electromagnetic radiation (RF-EMR). Rats were divided into two groups: control (n = 10, 4 replicates per test) and RF-EMR exposed group (n = 10, 4 replicates per test). Nociceptive responses of the groups were measured using rodent analgesiometry. Rats were divided into control and RF-EMR exposed groups. Nociceptive responses were measured using rodent analgesiometry. RF-EMR exposed rats had a 15% delay in responding to hot plate thermal stimulation compared to unexposed rats. The delay in responding to radiant heat thermal stimulation was 21%. We determined that RF-EMR promoted the occurrence of pressure pain as statistical significance by + 42% (p < 0.001). We observed that RF-EMR exposure increased nociceptive pain by + 35% by promoting cold plate stimulation (p < 0.05). RF-EMR exposure did not affect thermal preference as statistical significance but did support the formation of pressure pain perception.

In this study, we present data on pain perception in rats exposed to 6GHz RF-EMR. RF-EMR exposed rats showed delayed responses to hot plate and radiant heat thermal stimulation. RF-EMR increased pressure and nociceptive pain as statistically significance. In particular, the effects of RF-EMR should be considered when assessing hyperalgesic and hypoalgesic symptoms in the clinic. The results of this study indicate the need to take precautions against the possible negative effects of RF-EMR on human health with the rise of 5G technology.

Single Session Effects of Prolonged Continuous Theta Burst Stimulation Targeting Two Brain Regions on Pain Perception in Patients with Painful Diabetic Neuropathy: A Preliminary Study.

BACKGROUND: Painful diabetic neuropathy (pDN) is the most common cause of neuropathic pain (NP) in the United States. Prolonged continuous theta burst stimulation (pcTBS), a form of repetitive transcranial magnetic stimulation (rTMS), is quick (1-4 minutes) and tolerable for most individuals, compared to high frequency rTMS and can modulate pain thresholds in healthy participants. However, its effects on patients with chronic pain are still unclear. The primary purpose of this preliminary study is to investigate the effects of single session pcTBS targeted at the primary motor cortex (M1) and dorsolateral prefrontal cortex (DLPFC) on a set of self-report measures of pain (SRMP) that assess the (a) sensory-discriminative; (b) affective-motivational; and (c) cognitive-evaluative aspects of pain experience. METHODS: For this prospective, single-blind study, forty-two participants with pDN were randomized to receive either pcTBS targeting the M1 or the DLPFC brain regions. SRMP were completed at baseline, post pcTBS and 24h-post pcTBS. A two-way mixed model repeated measures analysis of variance (2 brain regions by 3 time points) was conducted to evaluate the effects of pcTBS stimulation at M1 and DLPFC for each subscale of each SRMP. RESULTS: After a single session of pcTBS targeted at M1 or DLPFC in patients with pDN, statistically significant improvements from baseline to post pcTBS and baseline to 24 h-post pcTBS were observed for different SRMP subscales examining the (a) sensory-discriminative, (b) affective-motivational and (c) cognitive-evaluative components of the pain experience. At 24 h-post pcTBS, none of the participants reported any serious adverse events to the pcTBS treatment, thus demonstrating its feasibility. CONCLUSIONS: In pDN patients with NP, our study results demonstrated significant improvement in scores on self-report measures of pain (SRMP) after a single session of pcTBS targeting the M1 and DLPFC brain regions. Future studies should consider utilizing multiple sessions of pcTBS to evaluate its long-term effects on pain perception, safety and tolerability in patients with chronic pain. CLINICAL TRIAL REGISTRATION: This study was registered on the ClinicalTrials.gov website (NCT04988321).

Acute effects of negative heel shoes on perceived pain and knee biomechanical characteristics of runners with patellofemoral pain.

BACKGROUND: To determine the effects of negative heel shoes on perceived pain and knee biomechanical characteristics of runners with patellofemoral pain (PFP) during running. METHODS: Sixteen runners with PFP ran in negative (-11 mm drops) and positive (5 mm drops) heel shoes while visual analog scale (VAS) scores, retroreflective markers, and ground reaction force were acquired by applying a 10-cm VAS, infrared motion capture system, and a three-dimensional force plate. Knee moment, patellofemoral joint stress (PFJS), and other biomechanical parameters during the stance phase were calculated based on inverse dynamics and a biomechanical model of the patellofemoral joint. RESULTS: The foot inclination angle, peak PFJS during the stance phase, patellofemoral joint reaction force, knee extension moment, and quadriceps force at the time of peak PFJS of runners with PFP in negative heel shoes were lower than that in positive heel shoes, no significant difference was found in VAS scores, knee flexion angle, patellofemoral contact area, and quadriceps moment arm at the time of peak PFJS. CONCLUSIONS: Compared to positive heel shoes, running in negative heel shoes decreases peak PFJS in runners with PFP, which may decrease patellofemoral joint loading, thus reducing the possibility of further development of PFP. TRAIL REGISTRATION: Sports Science Experiment Ethics Committee of Beijing Sport University. 2023095H, April 18, 2023 (prospectively registered).

Can the neural representation of physical pain predict empathy for pain in others?

The question of whether physical pain and vicarious pain have some shared neural substrates is unresolved. Recent research has argued that physical and vicarious pain are represented by dissociable multivariate brain patterns by creating biomarkers for physical pain (Neurologic Pain Signature, NPS) and vicarious pain (Vicarious Pain Signature, VPS), respectively. In the current research, the NPS and two versions of the VPS were applied to three fMRI datasets (one new, two published) relating to vicarious pain which focused on between-subject differences in vicarious pain (Datasets 1 and 3) and within-subject manipulations of perspective taking (Dataset 2). Results show that (i) NPS can distinguish brain responses to images of pain vs no-pain and to a greater extent in vicarious pain responders who report experiencing pain when observing pain and (ii) neither version of the VPS mapped on to individual differences in vicarious pain and the two versions differed in their success in predicting vicarious pain overall. This study suggests that the NPS (created to detect physical pain) is, under some circumstances, sensitive to vicarious pain and there is significant variability in VPS measures (created to detect vicarious pain) to act as generalizable biomarkers of vicarious pain.

Integration of Prior Expectations and Suppression of Prediction Errors During Expectancy-Induced Pain Modulation: The Influence of Anxiety and Pleasantness.

Pain perception arises from the integration of prior expectations with sensory information. Although recent work has demonstrated that treatment expectancy effects (e.g., placebo hypoalgesia) can be explained by a Bayesian integration framework incorporating the precision level of expectations and sensory inputs, the key factor modulating this integration in stimulus expectancy-induced pain modulation remains unclear. In a stimulus expectancy paradigm combining emotion regulation in healthy male and female adults, we found that participants' voluntary reduction in anticipatory anxiety and pleasantness monotonically reduced the magnitude of pain modulation by negative and positive expectations, respectively, indicating a role of emotion. For both types of expectations, Bayesian model comparisons confirmed that an integration model using the respective emotion of expectations and sensory inputs explained stimulus expectancy effects on pain better than using their respective precision. For negative expectations, the role of anxiety is further supported by our fMRI findings that (1) functional coupling within anxiety-processing brain regions (amygdala and anterior cingulate) reflected the integration of expectations with sensory inputs and (2) anxiety appeared to impair the updating of expectations via suppressed prediction error signals in the anterior cingulate, thus perpetuating negative expectancy effects. Regarding positive expectations, their integration with sensory inputs relied on the functional coupling within brain structures processing positive emotion and inhibiting threat responding (medial orbitofrontal cortex and hippocampus). In summary, different from treatment expectancy, pain modulation by stimulus expectancy emanates from emotion-modulated integration of beliefs with sensory evidence and inadequate belief updating.

Effect of photobiomodulation therapy on pain perception during anesthetic puncture of dental local anesthesia: A systematic review.

BACKGROUND: Local anesthetic puncture is often related to the experience of pain. This study aimed to systematically analyze the literature on changes in pain perception during the anesthetic puncture of dental local anesthesia after Photobiomodulation Therapy (PBMT). MATERIAL AND METHODS: An electronic search was performed in eight primary databases (Embase, LILACS, BBO, LIVIVO, MedLine via PubMed, SciELO, Scopus, and Web of Science) and three additional ones (EASY, Google Scholar, and OATD) to partially capture the "gray literature". The PICO strategy was used to identify randomized clinical trials evaluating the analgesic effect of PBMT in the anesthetic puncture site of dental local anesthesia compared to placebo or control groups, without restrictions on publication language and year. Two reviewers extracted the data and assessed the individual risk of bias of the eligible studies using the Cochrane Collaboration Risk of Bias Tool version 2.0. RESULTS: The electronic search found 3,485 records, of which eight met the eligibility criteria and were included in the qualitative synthesis. The studies were published from 2011 to 2022. None of the included studies had a low risk of bias. PBMT groups showed no significant difference in pain scores compared to placebo and control groups of most studies. CONCLUSION: Based on a low to very low certainty of evidence, PBMT seems to have no effect on pain perception during anesthetic puncture in patients undergoing dental local anesthesia.

Pain catastrophizing in the elderly: An experimental pain study.

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

The effectiveness of customised 3D-printed insoles on perceived pain, comfort, and completion time among frequent Park Runners: Study protocol for a pragmatic randomised controlled trial (The ZOLES RCT).

BACKGROUND: Running, a popular recreational activity, often leads to the experience of pain and discomfort among participants impacting performance and participation longevity. The ZOLES trial evaluates customised 3D-printed insoles for reducing pain in frequent parkrunners aged 35 and over. An innovative process of foot-scanning and responses to questions relating to size, pain, discomfort, and previous medical conditions are combined leading to the production of personalised 3D-printed orthotics. METHODS: The ZOLES trial is a pragmatic, outcome assessor blinded, randomised, controlled, superiority trial involving 200 recreational runners, randomised to receive either customised 3D-printed insoles (ZOLES) or to a "do-as-usual" control group. The study follows a robust protocol, ensuring adherence to established guidelines for clinical trials, and is based at St Mary's University, Twickenham, London. The primary outcome is change in running-related pain over a 10-week period, assessed using an 11-point Numeric Rating Scale. Secondary outcomes include overall pain and discomfort, running-related comfort, 5k-completion time, time-loss due to injuries, running exposure, and adherence to the intervention. A balanced-block randomisation process is stratified by sex and parkrun location, and an intention-to-treat analyses will be employed on all outcomes in the primary trial report. The trial includes a 52-week post-market surveillance to assess long-term effects of the customised insoles. DISCUSSION: The ZOLES trial aims to provide insights into real-world applicability and effectiveness of customised 3D-printed insoles in reducing running-related pain and enhancing overall running experience. Despite the limitation of a subjective primary outcome measure without participant blinding, the methodological rigor, including external outcome assessment and data handling, we anticipate results that are academically credible and applicable in real-world settings The results of this trial may have important implications for runners, clinicians, and the sports footwear industry, as evidence for the use of individualised insoles to improve running experience and prevention of pain may become evident. TRIAL REGISTRATION: The trial was pre-registered at ClinicalTrials.gov with the trial identifier NCT06034210 on September 4, 2023, and publicly posted on September 13, 2023 (https://clinicaltrials.gov/study/NCT06034210). PROTOCOL VERSION: Version 1, September 27, 2023.

Effects of functional polymorphisms of opioid receptor mu 1 and catechol-O-methyltransferase on the neural processing of pain.

AIM: Pain is reconstructed by brain activities and its subjectivity comes from an interplay of multiple factors. The current study aims to understand the contribution of genetic factors to the neural processing of pain. Focusing on the single-nucleotide polymorphism (SNP) of opioid receptor mu 1 (OPRM1) A118G (rs1799971) and catechol-O-methyltransferase (COMT) val158met (rs4680), we investigated how the two pain genes affect pain processing. METHOD: We integrated a genetic approach with functional neuroimaging. We extracted genomic DNA information from saliva samples to genotype the SNP of OPRM1 and COMT. We used a percept-related model, in which two different levels of perceived pain intensities ("low pain: mildly painful" vs "high pain: severely painful") were employed as experimental stimuli. RESULTS: Low pain involves a broader network relative to high pain. The distinct effects of pain genes were observed depending on the perceived pain intensity. The effects of low pain were found in supramarginal gyrus, angular gyrus, and anterior cingulate cortex (ACC) for OPRM1 and in middle temporal gyrus for COMT. For high pain, OPRM1 affected the insula and cerebellum, while COMT affected the middle occipital gyrus and ACC. CONCLUSION: OPRM1 primarily affects sensory and cognitive components of pain processing, while COMT mainly influences emotional aspects of pain processing. The interaction of the two pain genes was associated with neural patterns coding for high pain and neural activation in the ACC in response to pain. The proteins encoded by the OPRM1 and COMT may contribute to the firing of pain-related neurons in the human ACC, a critical center for subjective pain experience.

The value of pupillary diameter in evaluating pain perception after awakening in patients undergoing general anesthesia during orthopedic surgery.

BACKGROUND: The pupillary response to tetanic electrical stimulation reflects the balance between nociceptive stimulation and analgesia. Although pupillary pain index (PPI) was utilized to predict postoperative pain, it depended on tetanic stimulation and was complex. We aim to describe the potential relationship between PD in the presence of surgical stimulation and pain levels after awakening. METHODS: According to the Verbal Rating Scale (VRS) score after extubation, the patients were divided into painless group (VRS = 0) and pain group (VRS ≥ 1). Pupillary diameter (PD) and pupillary light reflex velocity (PLRV) were compared between two groups when patients entered the operating room (T1), before incision (T2), 10 s after incision (T3), 30 s after incision (T4), 1 h after incision (T5), at the end of surgery (T6), shortly after extubation (T7), and when patients expressed pain clearly (T8). The magnitude of PD change (ΔPD) compared to the baseline value after anesthesia induction (T2) was calculated. The correlations between pupillary parameters and pain after awakening were calculated. RESULTS: Patients with VRS ≥ 1 had greater PD than painless patients at T3-7 (P = 0.04, 0.04, 0.003, <0.001, <0.001), and it was positively correlated with VRS score after awakening at T4-7 (r = 0.188, 0.217, 0.684, 0.721). The ability of T6ΔPD to predict VRS ≥ 1 was strong [threshold: 20.53%, area under the curve (AUC): 0.93, 95% confidence interval (CI): 0.89-0.97 ]. CONCLUSION: Our study indicates that PD is a useful index to direct the individualized analgesics used during operation, to better avoid the occurrence of pain during the postoperative emergence period. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR2000040908, registration date: 15/12/2020).

Gender differences in pain perception among burning mouth syndrome patients: a cross-sectional study of 242 men and 242 women.

Several orofacial painful conditions are influenced by gender-related factors, but no studies are available with regard to Burning Mouth Syndrome (BMS). The present study aimed at investigating gender differences among BMS patients and their influence on pain perception. 242 BMS males (BMSm) and 242 BMS females (BMSf) matched for age were consecutively enrolled. Sociodemographic and clinical characteristics were recorded and the numeric rating scale (NRS), the Total Pain Rating Index (T-PRI), the Hamilton rating scale for anxiety and depression (HAM-A, HAM-D), the Pittsburgh sleep quality index (PSQI) and the Epworth sleepiness scale (ESS) were administered. The BMSm presented statistically significant higher levels of education and rate of employment compared to the BMSf (p-values: 0.001**). Moreover, the BMSm were greater consumers of alcohol and had a higher BMI than the BMSf (p-values: < 0.001**, 0.034*). With respect to systemic comorbidities, cardiovascular diseases were statistically more prevalent among the BMSm, while hypothyroidism was more frequent in the BMSf (p-vales: < 0.001**). No differences were noted between the two groups in terms of oral symptoms and in the median scores of NRS, T-PRI, HAM-A, HAM-D, PSQI and ESS. Interestingly, the multivariate regression analysis revealed that, while anxiety, high BMI, poor sleep and high level of T-PRI were correlated to the intensity of pain (NRS) in both groups, low education was additional predictor of pain in BMSf. Further, depression, alcohol and intensity of pain were factors positively associated to the quality of pain (T-PRI) in the BMSm, whereas low education, non-married status and NRS were correlated to the T-PRI, in the BMSf. Surprisingly, smoking was inversely correlated to the intensity of pain and quality of pain respectively in BMSf and BMSm. Sociodemographic and risk factors were found to differently influence pain perception in BMSm and BMSf. Therefore, clinicians should take into account gender differences in the assessment of BMS patients to better tailor the overall pain management.

Neuroimaging-based evidence for sympathetic correlation between brain activity and peripheral vasomotion during pain anticipation.

Anticipation of pain engenders anxiety and fear, potentially shaping pain perception and governing bodily responses such as peripheral vasomotion through the sympathetic nervous system (SNS). Sympathetic innervation of vascular tone during pain perception has been quantified using a peripheral arterial stiffness index; however, its innervation role during pain anticipation remains unclear. This paper reports on a neuroimaging-based study designed to investigate the responsivity and attribution of the index at different levels of anticipatory anxiety and pain perception. The index was measured in a functional magnetic resonance imaging experiment that randomly combined three visual anticipation cues and painful stimuli of two intensities. The peripheral and cerebral responses to pain anticipation and perception were quantified to corroborate bodily responsivity, and their temporal correlation was also assessed to identify the response attribution of the index. Contrasting with the high responsivity across levels of pain sensation, a low responsivity of the index across levels of anticipatory anxiety revealed its specificity across pain experiences. Discrepancies between the effects of perception and anticipation were validated across regions and levels of brain activity, providing a brain basis for peripheral response specificity. The index was also characterized by a 1-s lag in both anticipation and perception of pain, implying top-down innervation of the periphery. Our findings suggest that the SNS responds to pain in an emotion-specific and sensation-unbiased manner, thus enabling an early assessment of individual pain perception using this index. This study integrates peripheral and cerebral hemodynamic responses toward a comprehensive understanding of bodily responses to pain.