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.

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. 

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.

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.

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.

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.

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).

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.

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.

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.

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).

Low-Intensity Focused Ultrasound to the Human Dorsal Anterior Cingulate Attenuates Acute Pain Perception and Autonomic Responses.

The dorsal anterior cingulate cortex (dACC) is a critical brain area for pain and autonomic processing, making it a promising noninvasive therapeutic target. We leverage the high spatial resolution and deep focal lengths of low-intensity focused ultrasound (LIFU) to noninvasively modulate the dACC for effects on behavioral and cardiac autonomic responses using transient heat pain stimuli. A N = 16 healthy human volunteers (6 M/10 F) received transient contact heat pain during either LIFU to the dACC or Sham stimulation. Continuous electroencephalogram (EEG), electrocardiogram (ECG), and electrodermal response (EDR) were recorded. Outcome measures included pain ratings, heart rate variability, EDR response, blood pressure, and the amplitude of the contact heat-evoked potential (CHEP).LIFU reduced pain ratings by 1.09 ± 0.20 points relative to Sham. LIFU increased heart rate variability indexed by the standard deviation of normal sinus beats (SDNN), low-frequency (LF) power, and the low-frequency/high-frequency (LF/HF) ratio. There were no effects on the blood pressure or EDR. LIFU resulted in a 38.1% reduction in the P2 CHEP amplitude. Results demonstrate LIFU to the dACC reduces pain and alters autonomic responses to acute heat pain stimuli. This has implications for the causal understanding of human pain and autonomic processing in the dACC and potential future therapeutic options for pain relief and modulation of homeostatic signals.

Does brain entrainment using binaural auditory beats affect pain perception in acute and chronic pain?: a systematic review.

BACKGROUND: Pain is a major clinical problem across all ages with serious social and economic consequences and a great negative impact on quality of life. Brain entrainment using binaural beats is a non-pharmaceutical intervention that is claimed to have analgesic effects in acute and chronic pain. We aimed to systematically review the available randomized clinical trials on the efficacy of binaural auditory beats in reducing adults' pain perception in acute and chronic pain. A systematic search in electronic databases including Medline (via PubMed), Web of Science, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase was performed. The search was completed through Google Scholar and a manual search of the reference lists of all included studies. Randomized clinical trials with full text available in English that investigated the effect of binaural auditory beats on pain perception in acute and chronic pain in adults were included. The risk of bias was assessed by the revised Cochrane risk-of-bias (RoB 2) tool. Furthermore, The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach was used to assess the quality of the evidence. Sixteen studies (three on chronic pain and thirteen on acute pain perception) fulfilled the eligibility criteria. Because of substantial heterogeneity of the studies, a meta-analysis was inappropriate and this review focused on the narrative interpretation of the results. The risk of bias in most studies was high and the quality of evidence was low to very low. Although the effects of binaural beats on pain perception seem to be influenced by the etiology of pain or medical procedures, our review identifies alpha or a combination of tones in the range of delta to alpha as a potential non-pharmacological intervention in reducing acute pain. However, drawing a conclusion regarding the efficacy of binaural beats for chronic pain requires more high-quality studies. REGISTRATION: The protocol of this review was registered in PROSPERO (No. CRD42023425091).

Immune and metabolic challenges induce changes in pain sensation and related pathways in the hypothalamus.

The hypothalamic molecular processes participate in the regulation of the neuro-immune-endocrine system, including hormone, metabolite, chemokine circulation, and corresponding physiological and behavioral responses. RNA-sequencing profiles were analyzed to understand the effect of juvenile immune and metabolic distress 100 days after virally elicited maternal immune activation during gestation in pigs. Over 1,300 genes exhibited significant additive or interacting effects of gestational immune activation, juvenile distress, and sex. One-third of these genes presented multiple effects, emphasizing the complex interplay of these factors. Key functional categories enriched among affected genes included sensory perception of pain, steroidogenesis, prolactin, neuropeptide, and inflammatory signaling. These categories underscore the intricate relationship between gestational immune activation during gestation, distress, and the response of hypothalamic pathways to insults. These effects were sex-dependent for many genes, such as Prdm12, Oprd1, Isg20, Prl, Oxt, and Vip. The prevalence of differentially expressed genes annotated to proinflammatory and cell cycle processes suggests potential implications for synaptic plasticity and neuronal survival. The gene profiles affected by immune activation, distress, and sex pointed to the action of transcription factors SHOX2, STAT1, and REST. These findings underscore the importance of considering sex and postnatal challenges when studying causes of neurodevelopmental disorders and highlight the complexity of the "two-hit" hypothesis in understanding their etiology. Our study furthers the understanding of the intricate molecular responses in the hypothalamus to gestational immune activation and subsequent distress, shedding light on the sex-specific effects and the potential long-lasting consequences on pain perception, neuroendocrine regulation, and inflammatory processes.NEW & NOTEWORTHY The interaction of infection during gestation and insults later in life influences the molecular mechanisms in the hypothalamus that participate in pain sensation. The response of the hypothalamic transcriptome varies between sexes and can also affect synapses and immune signals. The findings from this study assist in the identification of agonists or antagonists that can guide pretranslational studies to ameliorate the effects of gestational insults interacting with postnatal challenges on physiological or behavioral disorders.

Effect of Remimazolam on Pain Perception and Opioid-Induced Hyperalgesia in Patients Undergoing Laparoscopic Urologic Surgery-A Prospective, Randomized, Controlled Study.

Background and Objectives: The effects of midazolam, a benzodiazepine, on pain perception are complex on both spinal and supraspinal levels. It is not yet known whether remimazolam clinically attenuates or worsens pain. The present study investigated the effect of intraoperative remimazolam on opioid-induced hyperalgesia (OIH) in patients undergoing general anesthesia. Materials and Methods: The patients were randomized into three groups: group RHR (6 mg/kg/h initial dose followed by 1 mg/kg/h remimazolam and 0.3 µg /kg/min remifentanil), group DHR (desflurane and 0.3 µg /kg/min remifentanil) or group DLR (desflurane and 0.05 µg/kg /min remifentanil). The primary outcome was a mechanical hyperalgesia threshold, while secondary outcomes included an area of hyperalgesia and clinically relevant pain outcomes. Results: Group RHR had a higher mechanical hyperalgesia threshold, a smaller hyperalgesia postoperative area at 24 h, a longer time to first rescue analgesia (p = 0.04), lower cumulative PCA volume containing morphine postoperatively consumed for 24 h (p < 0.01), and lower pain intensity for 12 h than group DHR (p < 0.001). However, there was no significant difference in OIH between groups RHR and DLR. Conclusions: Group RHR, which received remimazolam, attenuated OIH, including mechanically evoked pain and some clinically relevant pain outcomes caused by a high dose of remifentanil. Further research is essential to determine how clinically meaningful and important the small differences observed between the two groups are.

The prophylactic effect of photobiomodulation therapy on pain perception due to infiltration injection: a randomized clinical trial.

OBJECTIVES: Fear of pain in dentistry especially the injection involved in most of the processes has always been an important issue preventing the patients from consulting a dentist at the right time. This study aims to evaluate the effect of photobiomodulation therapy on reduction of pain in infiltration injection. MATERIALS AND METHODS: This trial is a crossover study including 30 patients. The patients are divided into two groups (laser therapy in the first period and placebo effect in the next period or vice versa with split-mouth design) using the covariate adaptive randomization method. All the patients received bilateral maxillary canine anesthesia in two periods performed with an ICT injection device (amount of anesthesia solution loaded: 1.8 mL) at a speed of 1 mL/min and a temperature of the solution of 37 °C. In each period, patients received either a prophylactic dose of 940-nm laser (500 mW, 10 J/cm2) or its placebo effect before the injection. The degree of pain perception after each sort of treatment is evaluated by both SEM (Sound, Eye, Motor, and Pain) and VAS (Visual Analogue Scale) scales. RESULTS: According to analysis, all the patients scored a VAS scale under 3 in the period they received intervention. Also considering the SEM scale, most of the patients scored 0 in the intervention period. No adverse effect was reported during or after the process. CONCLUSIONS: The study showed a significant effect of photobiomodulation on reducing pain perception during infiltration injection. CLINICAL RELEVANCE: This method can be useful in order to lower the pain for the patients consulting a dentist and therefore facilitate consulting at early stages of the dental issues. TRIAL REGISTRATION: The registration number (date) of the clinical trial in a Primary Registry in the WHO Registry Network is IR.ARAKMU.REC.1398.248(13/03/2020). The related URL is https://en.irct.ir/trial/45362 .

Pain perception and analgesic use after cesarean delivery among women with endometriosis.

BACKGROUND: Patients with endometriosis are known to have altered pain perceptions. Cesarean delivery (CD) is one of the most prevalent surgeries performed worldwide. Appropriate pain control following CD is clinically important to the recovery and relief of patients. This study assessed pain perception and analgesic use after CD among women with or without endometriosis. METHODS: This retrospective case control study included women diagnosed with endometriosis, based on clinical or surgical findings, who underwent CD from 2014 to 2022. Controls were matched to the study group by maternal age, BMI (kg/m2), parity, number of previous CDs and by CD indication, in a 2:1 ratio. Post-operative visual analogue scale (VAS) pain scores, on each post-operative day (POD) were compared between groups. Pain intensity was measured and compared using the VAS, range 0 (no pain) to 10 (worst pain). The standard pain relief analgesia protocol in our department includes fixed oral treatment with paracetamol and diclofenac, with the addition of morphine sulphate on POD 0. Analgesic dosages used and the percentage of patients not using the full standard analgesic protocol were compared between groups. RESULTS: As compared to controls (n = 142), the endometriosis group (n = 71) was characterized by higher rates of in-vitro fertilization (IVF) pregnancies and previous abdominal surgeries other than CD (p < .001 for both). Other maternal characteristics between groups did not differ. On POD 0, mean morphine dosage was significantly higher in the endometriosis group compared to the control group (24 mg vs. 22.8 mg, respectively; p = .044). More patients in the endometriosis group used the full standard analgesia protocol or more, as compared to controls. VAS scores were not significantly different between groups. CONCLUSIONS: Increased use of analgesics after CD was more common among women with endometriosis. These findings imply that pain relief protocols should be personalized for women with endometriosis.