Pain Threshold Tolerance Research Articles

Transcranial Direct Current Stimulation Reduces Pressure Pain Sensitivity in Patients With Noncancer Chronic Pain.

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

Randomized, placebo-controlled study on the effects of intravenous GSK3858279 (anti-CCL17) on a battery of evoked pain tests in healthy participants.

C-C Motif Chemokine Ligand 17 (CCL17) is a chemokine that binds and signals through the G-protein coupled CC-chemokine receptor 4 and has been implicated in the development of inflammatory and arthritic pain. GSK3858279 is a high-affinity, first-in-class, monoclonal antibody, binding specifically to CCL17 and inhibiting downstream signaling. In this phase I, randomized, single-center, double-blind, placebo-controlled, three-period, incomplete-block crossover study (NCT04114656), the analgesic effects and safety of intravenous GSK3858279 were assessed in a battery of evoked acute pain assessments on healthy, adult (aged ≥18 years), male participants. Participants were randomized 1:1 to receive either one placebo (0.9% w/v NaCl) dose followed by two GSK3858279 doses (PAA treatment sequence), or one GSK3858279 dose followed by two placebo doses (APP treatment sequence). The co-primary end points were ultraviolet B heat pain detection threshold (°C), cold pressor time to pain tolerance threshold (PTT, sec), and electrical PTT (mA, single stimulus). Twenty-one participants were enrolled (PAA = 11; APP = 10). Mean age (standard deviation) was 29.3 (7.9) years for PAA, 31.1 (7.7) years for APP. No significant differences were observed in the analgesic effect between GSK3858279 and placebo for any end point. Exposure to GSK3858279 was similar between Period 1 (APP sequence), and Periods 2 and 3 (PAA sequence), with some GSK3858279 carry-over. Changes in serum CCL17 levels were consistent with the expected GSK3858279 activity. All drug-related adverse events were mild in intensity and caused no discontinuations. The absence of an efficacy signal in this acute pain model does not preclude efficacy in chronic pain states.

Pressure algometry in the general adult population: Age and sex differences.

Experimental pain studies have revealed inter-individual variations in pain perception that are influenced by age, sex, and country of origin. This study aimed to explore the age and sex differences in pressure pain thresholds within the Iranian general population. To assess the pressure pain thresholds, a handheld pressure algometer was applied bilaterally to the middle fingers of both hands. The participants also completed the short form of the McGill Pain Questionnaire to provide a clinical pain rating. This cross-sectional study included 1610 adult subjects (54.96% female, mean age 40.13 ± 10.18 years). The findings indicated that females generally exhibited lower pain thresholds than males when assessing pain detection and tolerance parameters (P < .001). Females also demonstrated a significant lower pressure thresholds and clinical pain ratings compared with men (P < .001). Additionally, significant differences were observed between age groups in terms of pain detection and tolerance thresholds (P = .02 and P = .03, respectively). However, the interaction between sex and age was not significant. No significant differences in pain detection thresholds were observed between the right and left hand (P = .11). This study underscores the potential utility of algometry as a valuable tool for objectifying pain in the Iranian population.

Adenosine triphosphate mediates the pain tolerance effect of manual acupuncture at Zusanli (ST36) in mice.

To investigate the mechanisms behind the effects of acupuncture in Traditional Chinese Medicine, we delved into the adenosine triphosphate/peripheral purinergic P2X receptor 3 (ATP/P2X3) receptor signaling system as an indicator of the body's energy state, commonly referred to as "Qi". The tail-flick test was utilized to explore the impact of acupuncture on pain tolerance threshold (PTT) in mice, while also assessing adenosine (ADO) levels and adenylate energy charge (EC) at Zusanli (ST36). The study further investigated the dose-dependent effects of acupuncture on PTT and ADO levels at Zusanli (ST36). To shed light on the underlying mechanisms of acupuncture's effects, the study examined the impact of ATP, a P2X3 receptor antagonist, and adenosine disodium on PTT following acupuncture administration. Acupuncture at Zusanli (ST36) led to significant improvements in PTT in mice, with the most effective interventions being twirling for 2 min and needle retention for 28 min. These interventions also resulted in significant increases in ATP levels. The effects of acupuncture were further augmented by administration of different doses of ATP at Zusanli (ST36), and pretreatment with a P2X3 receptor antagonist decreased PTT. Adenylate EC peaked at 30 min after intraperitoneal injection of ATP, and pretreatment with various doses of i.p. ATP 30 min prior to acupuncture increased PTT in a dose-dependent manner. Additionally, pretreatment with an i.p. or intramuscular injection of adenosine disodium enhanced the effects of acupuncture. This research provides compelling evidence that ATP is involved in the regulation of PTT through acupuncture, revealing new avenues for achieving enhanced clinical outcomes.

Epidural methadone and morphine pharmacokinetics and clinical effects in healthy volunteers: A randomized, crossover-design trial.

Epidural opioids can provide effective analgesia for acute postoperative pain. Due to its unique physicochemical properties and long systemic elimination half-life, epidural methadone may provide lasting analgesia with minimal adverse effects; however, human studies are lacking. The aim of the study was to test the hypothesis that epidural methadone would exhibit greater segmental analgesia (analgesia at the dermatome of injection vs. distant dermatomes) than epidural morphine. In a prospective, randomized, double-blinded, crossover study, thirteen healthy volunteers received a 4-mg epidural bolus of methadone or morphine at L3-L4 and underwent repeated assessment of dermatomal heat pain tolerance and pressure pain threshold at lumbar (L3) and trigeminal (V2) dermatomes, pupil diameter, respiratory parameters and venous opioid concentration for 24 h. The primary outcome was selective (lumbar vs. trigeminal) segmental analgesia for heat pain, as a marker of a spinal analgesic mechanism. The degree of segmental analgesia to heat pain tolerance was not different between morphine and methadone (P =.09), although morphine (P =.0009) but not methadone (P =.81) produced significant analgesia to heat pain at the lumbar vs. trigeminal dermatome over 0-12 h. Morphine overall provided longer lasting analgesia to heat pain vs. methadone (24 vs. 2 h, respectively). Morphine elicited greater systemic effects, including miosis (P =.009) and opioid-related adverse effects (P =.002). These results suggest that, with equal epidural doses, both methadone and morphine produced analgesia and methadone did not produce greater segmental effects than morphine. Epidural methadone provided a more favourable adverse effect profile.

Enhancing treatment of lumbar disc herniation with Erxian decoction and auricular acupoint pressure: A randomized controlled trial.

The incidence of lumbar disc herniation (LDH) is on the rise annually, with an emerging trend of affecting younger age groups. This study aims to investigate the clinical effectiveness of combining Erxian decoction with auricular acupoint pressure therapy in treating LDH. Our objective is to furnish evidence supporting the incorporation of traditional Chinese medicine (TCM) rehabilitation techniques in clinical settings. This randomized controlled trial enrolled 102 patients diagnosed with LDH and allocated them into Control and Intervention groups. The Control group underwent a 2-week rehabilitation regimen, whereas the Intervention group received an augmented treatment comprising Erxian decoction along with auricular acupoint pressure therapy based on the Control group. Main outcome measures included 3 scales - visual analog scale (VAS), Japanese Orthopedic Association (JOA), and Oswestry Disability Index - as well as 3 inflammatory markers: C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Additionally, pressure pain threshold and pain tolerance threshold values were evaluated. Participants were assessed at baseline, on 14-day, and on 28-day posttreatment. After 2 weeks of treatment, both the Control and Intervention groups exhibited significant improvements in the VAS, JOA, ODI, CRP, IL-6, TNF-α, pressure pain threshold, and pain tolerance threshold (P < .05). These improvements persisted at the 28-day in the VAS, JOA, and ODI scores (P < .05). On 14-day, the Intervention group showed significantly better outcomes compared to the Control group in terms of the VAS, JOA, ODI, CRP, TNF-α, and pressure pain threshold (P < .05). Compared to conventional rehabilitation therapy, the combination of Erxian decoction and auricular acupoint pressure therapy demonstrates clear benefits in alleviating symptoms in patients with LDH. This approach offers fresh perspectives and substantiates evidence for future treatment strategies in managing LDH.

Modulation of multisensory nociceptive neurons in monkey cortical area 7b and behavioral correlates.

Wide-range thermoreceptive neurons (WRT-EN) in monkey cortical area 7b that encoded innocuous and nocuous cutaneous thermal and threatening visuosensory stimulation with high fidelity were studied to identify their multisensory integrative response properties. Emphasis was given to characterizing the spatial and temporal effects of threatening visuosensory input on the thermal stimulus-response properties of these multisensory nociceptive neurons. Threatening visuosensory stimulation was most efficacious in modulating thermal evoked responses when presented as a downward ("looming"), spatially congruent, approaching and closely proximal target in relation to the somatosensory receptive field. Both temporal alignment and misalignment of spatially aligned threatening visual and thermal stimulation significantly increased mean discharge frequencies above those evoked by thermal stimulation alone, particularly at near noxious (43°C) and mildly noxious (45°C) temperatures. The enhanced multisensory discharge frequencies were equivalent to the discharge frequency evoked by overtly noxious thermal stimulation alone at 47°C (monkey pain tolerance threshold). A significant increase in behavioral mean escape frequency with shorter escape latency was evoked by multisensory stimulation at near noxious temperature (43°C), which was equivalent to that evoked by noxious stimulation alone (47°C). The remarkable concordance of elevating both neural discharge and escape frequency from a nonnociceptive and prepain level by near noxious thermal stimulation to a nociceptive and pain level by multisensory visual and near noxious thermal stimulation and integration is an elegantly designed defensive neural mechanism that in effect lowers both nociceptive response and pain thresholds to preemptively engage nocifensive behavior and, consequently, avert impending and actual injurious noxious thermal stimulation.NEW & NOTEWORTHY Multisensory nociceptive neurons in cortical area 7b are engaged in integration of threatening visuosensory and a wide range of innocuous and nocuous somatosensory (thermoreceptive) inputs. The enhancement of neuronal activity and escape behavior in monkey by multisensory integration is consistent and supportive of human psychophysical studies. The spatial features of visuosensory stimulation in peripersonal space in relation to somatic stimulation in personal space are critical to multisensory integration, nociception, nocifensive behavior, and pain.

Assessing the effectiveness of high frequency repetitive transcranial magnetic stimulation for post-mastectomy pain in breast cancer patients: A randomized controlled trial.

Post-mastectomy pain Syndrome (PMPS), characterized by chronic neuropathic pain stemming from intercostobrachial nerve lesions, presents a formidable clinical challenge. With the incidence of breast cancer surging, effective interventions for PMPS are urgently needed. To address this, we conducted this double-blind, placebo-controlled, randomized clinical trial to study the efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) therapy over the motor cortex on pain, quality of life and thermal sensitivity in PMPS patients. We delivered 15 rTMS sessions over three weeks in a cohort of 34 PMPS patients. These patients were allocated randomly to either rTMS therapy or sham therapy groups. Pain assessments, utilizing the Visual Analogue Scale (VAS) and Short Form McGill Pain Questionnaire (SF-MPQ), alongside quality-of-life evaluations through the Functional Assessment of Cancer Therapy-Breast (FACT-B), were recorded before and after the 15 sessions. Additionally, we assessed thermal sensitivity using Quantitative Sensory Testing (QST). Our findings demonstrate the superior efficacy of rTMS therapy (over sham therapy) in reducing VAS and SF-MPQ scores (p < 0.0001), improving physical (p = 0.037), emotional (p = 0.033), and functional well-being (p = 0.020) components of quality of life, as quantified by FACT-B. Our investigation also unveiled marked enhancements in thermal sensitivity within the rTMS therapy group, with statistically significant improvements in cold detection threshold (p = 0.0001), warm detection threshold (p = 0.0033), cold pain threshold (p = 0.0078), and hot pain tolerance threshold (p = 0.0078). The study underscores the profound positive impact of rTMS therapy on pain, quality of life, and thermal sensitivity in patients havingPMPS, opening new avenues for pain management strategies.

Intraoperative pain prediction of percutaneous kyphoplasty under local anesthesia by preoperative experimental pain assessment.

Percutaneous kyphoplasty (PKP) is the preferred treatment for osteoporotic vertebral compression fractures (OVCF) Currently, the preoperative anesthesia methods for PKP are mainly local anesthesia and tracheal intubation general anesthesia. To assess whether patient sensitivity to pain measured preoperatively could predict the patients' pain response during PKP treatment under local anesthesia, to facilitate the development of an optimal preoperative anesthesia plan for patients. Fifty-five female patients diagnosed with osteoporotic single vertebral fracture who were treated with PKP under local anesthesia were selected. The patients' pain sensitivities, including pain threshold and pain tolerance threshold, were evaluated with a pain test device on the day before the operation in the ward. Heart rate (HR), mean arterial pressure (MAP), and blood oxygen saturation (SpO2) were recorded before anesthesia, post-anesthesia, after needle puncture, and after balloon dilatation. At the same time, blood was drawn at the above time points to determine the level of norepinephrine (NA) as an indicator of intraoperative pain stress response. The numerical rating scale (NRS) during surgery was recorded at the end of the surgery. The preoperative pain tolerance threshold of 55surgical patients was correlated with the intraoperative NRS score (r=-0.768, P< 0.001), as well as with the preoperative and intraoperative changes in HR (r=-0.791, P< 0.001), MAP (r=-0.819, P< 0.001), and NA (r=-0.553, P< 0.001). Thus, the lower the preoperative pain tolerance threshold, the more severe the patient's response to pain during PKP treatment under local anesthesia, and the greater the hemodynamic changes. Consequently, the intraoperative experience becomes worse. However, there was no correlation between preoperative pain threshold and NRS scores (r=-0.069, P= 0.616) nor between the preoperative and intraoperative changes in HR (r= 0.103, P= 0.453), MAP (r= 0.086, P= 0.535), and NA (r=-0.058, P= 0.674). The results indicated that preoperative pain assessment could predict the level of pain response in OVCF patients during PKP surgery under local anesthesia.

Linear and curvilinear association of pain tolerance and social anxiety symptoms among youth with different subgroups of childhood trauma

BackgroundSocial anxiety is a common symptom that occurs after exposure to childhood trauma (CT), and pain tolerance is a protective factor against social anxiety in generic populations with CT. However, few studies have investigated whether and how this association varies across different CT subgroups. Thus, this study aimed to investigate (1) the effects of pain tolerance on social anxiety symptoms among youth with different subgroups of CT; (2) the nonlinear relationship between pain tolerance and social anxiety symptoms among different CT categories. MethodsIn this study, 15,682 college or university students with experiences of CT were identified in a large sample and divided into five CT subgroups. Linear and quadratic regression models were conducted to explore the association between pain tolerance and social anxiety symptoms among youth with different CT subgroups. ResultsThe results of model revealed a linear relationship between pain tolerance and social anxiety symptoms among youth with most CT subgroups. Notably, an inverted U-shaped curve was found between pain tolerance and social anxiety symptoms in youth with emotional abuse. Social anxiety symptoms increased gradually with pain tolerance scores between 0 and 16, and then sharply decreased when scores reached above 16. LimitationsLimited by self-report measurements, the results of this study focused only on perceived pain tolerance and ignored behavioral pain tolerance. ConclusionThese findings highlight the importance of assessing pain tolerance thresholds in youth with emotional abuse and improving pain tolerance to prevent social anxiety symptoms in youth with different subgroups of CT.

Application of sensory nerve quantitative tests to analyze the subtypes of motor disorders in Parkinson's disease.

This study investigated the sensory nerve function in people with different subtypes of Parkinson's disease (PD), which included the tremor-dominant (TD) group (n = 30), postural instability and gait disorder (PIGD) group (n = 33), and healthy-controls (HC) group (n = 33). Sural nerve's current perception threshold (CPT) and pain tolerance threshold (PTT) in both feet were measured at different frequencies. Results were evaluated using the mini-mental state examination (MMSE), Hoehn Yahr scale (H-Y) , and 3-meter timed-up-and-go-test (TUGT). The MMSE scores of the TD and HC groups were higher than those of the PIGD group (TD < HC). The 3-meter TUGT scores of the PIGD group were higher than theTD and HC groups (TD > HC). The PIGD patients experienced a significantly shorter disease duration and higher H-Y score than the TD patients ( P < 0.05). The values of 2 KHz CPT of left-side (CPTL), 2KHz CPT of right-side (CPTR), and 5 Hz CPTR in the PIGD group were significantly higher compared to the TD and HC groups ( P < 0.05, Bonferroni correction). Additionally, the values of 250 Hz CPTL, 5 Hz CPTL, 250 Hz CPTR, 2 kHz PTT of left-side (PTTL), 250 Hz PTTL, and 5 Hz PTTL in the PIGD group were significantly elevated relative to the TD group ( P < 0.05, Bonferroni correction). Distinctive current threshold perception and PTT of the sural nerve can be observed in patients with varying PD subtypes, and sensory nerve conduction threshold electrical diagnostic testing can detect these discrepancies in sensory nerve function.

Predictive Modeling of The Chronic Pain-Induced Depression in Old Adults Based on Music Intervention

Chronic pain is a prevalent concern for older individuals, often leading to a decline in mental well-being, especially through conditions like depression. This study explores the potential effectiveness of Music Intervention (MI) as a non-pharmacological approach to alleviate depressive symptoms in those experiencing chronic pain. Existing methodologies lack predictive accuracy, prompting the introduction of the Predicting Chronic Pain-based Music Intervention (PCP-MI) model. Utilizing machine learning, the PCP-MI model customizes music treatments based on individual characteristics and preferences, showcasing promising results across various metrics related to pain, anxiety, heart and respiratory rates, pain tolerance, emotional well-being, quality of life, and depression severity. The PCP-MI method demonstrated a mean performance across multiple metrics, encompassing pain intensity (17.75%), anxiety level (27.79%), heart rate (78.30 bpm), respiratory rate (15.90 bpm), pain tolerance threshold (59.37 seconds), emotional well-being (75.56%), quality of life (74.81%), and depression severity (65.27%). This research suggests a promising avenue for enhancing the psychological well-being of a vulnerable group, representing a significant advancement in comprehensive pain treatment approaches.

Effects of an afforestation activity on thermal and mechanical pain mechanisms: A clinical trial

Sensory stimulation has shown the capacity to modulate pain mechanisms. Yet, the optimal methods of sensory stimulation remain uncertain. Afforestation activities stand out as a potential stimulation method, as they allow individuals to interact with multisensory stimuli produced in green environments. Exposure to natural multisensory stimuli has been shown to induce neurobiological activations in pain-related brain areas in healthy populations. However, the possible impact of the natural multisensory stimuli on the pain mechanisms themselves is yet to be explored. This study aimed to investigate the potential effects of sensory stimulation experienced during participation in an afforestation program on thermal and mechanical pain mechanisms. A single-group, pretest-posttest clinical trial was used. Forty-seven healthy adults performed an afforestation activity for 90 minutes. Measurements included cold pain detection and tolerance thresholds via the Cold Pressor Test, wind-up and mechanical pain sensitivity through a pinprick stimulator, and pressure pain detection and tolerance thresholds utilizing pressure algometry. For both thermal and mechanical pain thresholds, pain intensity was assessed using the 101-point Numeric Rating Scale. The results showed significant reductions in the cold pain intensity at the moment of detection (p = .046), mechanical pain sensitivity (p ≤ .014), and increases in the thresholds of pressure pain detection (p = .005) and tolerance (p ≤ .046). Therefore, the interaction with natural multisensory stimuli could be a possible therapeutic strategy to positively modulate mechanical pain sensitivity and pressure pain thresholds.

The Predictive Value of Cold Pack Test for Pain After Third Molar Surgery

Early identification of patients who are prone to postoperative pain may provide individualization of postoperative analgesia strategies. The aim of the study was to investigate whether the cold pack test is associated with postoperative pain levels after mandibular third molar surgery. This prospective cohort study included healthy male patients admitted to Department of Oral and Maxillofacial Surgery of a tertiary health-care center between June 2022 and December 2022 and scheduled for lower third molar extraction. Those who had used any analgesic within the past 10days or had a history of intolerance/allergy to analgesics were excluded. The primary predictor variable was pain tolerance, measured using the endurance test score. Subjects were grouped into two categories, low tolerance test score (withdrew the hand from the cold pack in <240seconds) and high tolerance test score (maintained the hand on the cold pack for 240seconds). The primary outcome variable was pain measured by the patients from 0 to 10 with the visual analog scale, and the secondary outcome variables were the amount of ibuprofen and paracetamol consumed in the postoperative period. Pain measurements and ibuprofen consumption were recorded at 0-2, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, and 96hours (0-2 interval of the first 2hours immediately after surgery). Age, classification and position of mandibular third molar were utilized as covariates. The relationship between pain tolerance and postoperative pain was analyzed using the Mann-Whitney U test and the Fisher exact test. Statistical analysis was performed using the SPSS version 28.0 software. A total of 30 male patients with a mean age of 22.5±4.8years were included in our study. In the group with low pain tolerance, the pain scores at the first 2hours, 32, and 48hours after the operation (4.55±3.59, 2.91±2.59, 2.91±2.43, respectively) were found to be significantly higher than the group with high pain tolerance (2.00±2.67, 0.95±1.68, 0.95±1.39, respectively) (P<.05). In the first 2hours after the operation, the amount of ibuprofen consumed was also significantly higher in the group with low pain tolerance compared to the other group, and 81.8% of this group felt the need to consume ibuprofen (P<.05). The cold pack test, a more practical version of quantitative sensory testing, is useful in identifying male patients at risk of developing greater pain after third molar surgery. It can be helpful to provide effective analgesia in male patients with different pain tolerance thresholds.

Bullying Involvement and Physical Pain Between Ages 10 and 13 Years: Reported History and Quantitative Sensory Testing in a Population-Based Cohort

We aimed to quantify the prospective association between bullying and physical pain in a population-based cohort of adolescents. We assessed 4,049 participants of the 10 and 13 years waves of the Generation XXI birth cohort study in Portugal. Pain history was collected using the Luebeck pain screening questionnaire. A subsample of 1,727 adolescents underwent computerized cuff pressure algometry to estimate pain detection/tolerance thresholds, temporal pain summation and conditioned pain modulation. Participants completed the Bully Scale Survey and were classified as “victim only”, “both victim and aggressor”, “aggressor only”, or “not involved”. Associations were quantified using Poisson or linear regression, adjusted for sex and adverse childhood experiences. When compared to adolescents “not involved”, participants classified as “victim only” or “both victim and aggressor” at age 10 had higher risk of pain with psychosocial triggers, pain that led to skipping leisure activities, multisite pain, pain of higher intensity, and pain of longer duration, with relative risks between 1.21 (95% confidence interval: .99, 1.49) and 2.17 (1.57, 3.01). “Victims only” at age 10 had lower average pain detection and tolerance thresholds at 13 years (linear regression coefficients: −1.81 [−3.29, −.33] and −2.73 [−5.17, −.29] kPa, respectively), as well as higher pain intensity ratings (.37 [.07, .68] and .39 [.06, .72] mm), when compared with adolescents not involved. No differences were seen for the remaining bullying profiles or sensory measures. Our findings suggest that bullying may have long-term influence on the risk of chronic musculoskeletal pain and may interfere with responses to painful stimuli. PerspectiveWe found prospective evidence that bullying victimization in youth: 1) is more likely to lead to negative reported pain experiences than the reverse, 2) may have long-term influence on adverse pain experiences, and 3) may contribute to pain phenotypes partly by interfering with somatosensory responses to painful stimuli.

Effects of virtual reality on psychophysical measures of pain: superiority to imagination and nonimmersive conditions.

Virtual reality (VR) has been shown to be effective in pain management. However, to date, little is known about the mechanisms by which immersive experiences influence pain processing. The aim of this study was to investigate the direct effects of an immersive VR environment on the perception of experimental pain in individuals with chronic pain and pain-free controls. The immersion in a VR landscape was compared with mental imagery and a nonimmersive control condition. Using a randomized within-crossover design, pressure pain detection and tolerance thresholds, spatial and temporal summation (SSP, TSP), and conditioned pain modulation (CPM) were measured in 28 individuals with chronic pain and 31 pain-free controls using phasic cuff pressure on the legs. Direct comparison between the groups showed that although individuals with pain had significantly lower pain thresholds, reduced CPM effects, and increased TSP, the VR condition had the same pain-inhibitory effect on pain thresholds as in pain-free controls. Conditioned pain modulation effects were reduced by all conditions compared with baseline. There were no significant differences between conditions and baseline for TSP and SSP. Overall, pain modulatory effects were largest for VR and smallest for imagery. These results demonstrate that immersion in a VR environment has an increasing effect on pain thresholds, reduces pain inhibition in a CPM paradigm, and has no effects on TSP. This applies for participants with chronic pain and pain-free controls. These VR effects exceeded the effects of mental imagery on the nonimmersive control condition. This indicates that VR effectively modulates pain perception in both patients and controls irrespective of differences in pain perception.

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

Sensitized pain mechanisms are often reported in musculoskeletal pain conditions, but population-based paediatric studies are lacking. We assessed whether adolescents with musculoskeletal pain history had evidence of increased responsiveness to experimental pressure stimuli. Data were from 1496 adolescents of the Generation XXI birth cohort. Pain history was collected using the Luebeck Pain Questionnaire (self-reported at 13, parent-reported at 7 and 10 years). Two case definitions for musculoskeletal pain were considered: (1) cross-sectional-musculoskeletal pain lasting more than 3 months at age 13 and (2) longitudinal-musculoskeletal pain at age 13 with musculoskeletal pain reports at ages 7 and/or 10. Lower limb cuff pressure algometry was used to assess pain detection and tolerance thresholds, conditioned pain modulation effects (CPM, changes in thresholds in the presence on painful conditioning) and temporal summation of pain effects (TSP, changes in pain intensity to 10 phasic painful cuff stimulations). Adolescents with musculoskeletal pain at age 13 plus a history of pain in previous evaluations (longitudinal definition) had lower pain tolerance thresholds compared to the remaining sample (40.2 v. 49.0 kPa, p = 0.02), but showed no differences in pain detection threshold, CPM effect and TSP effect. Pain sensitivity, CPM effects and TSP effects were not significantly different when the current pain only case definition (cross-sectional) was used. Adolescents with current musculoskeletal pain who had a history of pain since childhood had lower tolerance to cuff stimulation. This may suggest long-standing musculoskeletal pain since childhood may contribute to sensitisation, rather than the presence of current pain only. Repeated musculoskeletal pain up to age 13 years may contribute to higher pain sensitivity (particularly lowered pressure pain tolerance) in the general adolescent population. This does not seem to be the case when reported pain experiences are recent or when the outcomes are temporal pain summation or CPM. In this community-based paediatric sample, the vast majority showed no sign of altered pain processing, but a small fraction may reveal some pain sensitization at 13 years of age.

Study of humoral immunity indices for assessing physical exhaustion in sports

Studies of real opportunities for physical skills of athletes sufficiently depend on their adaptive potential for increasing physical loads. Extreme physical and psychoemotional loads may lead to overwork and decreased physical ability in professional sportsmen. These adaptation processes are regulated by the main biochemical systems of the body. A special role belongs to the factors of humoral immunity, i.e., natural antibodies, which are a component of innate immunity. They circulate in blood of healthy persons in absence of obvious antigenic stimulation. Analytical techniques for measuring the level of natural antibodies that reflect the state of the system of endogenous bioregulators involved into the molecular mechanisms of adaptation process have been developed. An important role among them is played by the regulators of the opioid system β-endorphin and orphanin. The biochemical and immunological parameters were determined in 10 athletes active in figure skating (Master of Sports), whose average age was 16±0.4 years, and sport experience of 9±1 years. The duration of the study was divided into 5 stages and was 62 days. During the dynamic observations in the course of intensive training, no clear shifts in biochemical parameters were revealed towards adaptation stress and delayed recovery. The level of natural antibodies to orphanin and beta-endorphin was measured in the athletes blood serum by ELISA techique. It is found that each athlete is characterized by individual immune profile. At the initial stage of the examination, the level of antibodies to beta-endorphin was within normal ranges, except for its decrease in one athlete. The level of antibodies to orphanin in majority of cases was higher than normal, probably, due to inhibitory control of the pain signal. Further study in time dynamics revealed that the immunological parameters, natural antibodies to opioid peptides, change in accordance with the state of adaptation resources in the athletes. These indexes reflect psycho-emotional potential and pain tolerance threshold for athletes from the start of training and throughout the entire period. Therefore, from a prognostic point of view, it is important to monitor the content of natural antibodies to beta-endorphin and orphanin in athletes in the course of training. Such individual monitoring of the athlete’s immunological indices allows us to select a more effective, personal training program.

Assessment of analgesic properties of alcohol and aqueous extracts of Opuntia ficus-indica flowers

The cactus (Opuntia ficus-indica (L.) Mill.) belongs to the Cactaceae family and it’s used in traditional folk medicine in treating a number of diseases and conditions. Due to the remarkable biological activity and to the bioactive (phytochemicals) compounds of O. ficus-indica, it becomes the aim of many research studies. The current study aimed to evaluate the analgesic activity of various solvent fractions (aqueous and ethanol) prepared from the O. ficus-indica flowers. The centrally analgesic potential was evaluated using tail flick latency in tail immersion and hot plate methods in mice. Morphine was used as a positive control at a dose of 3 mg kg-1, s.c.. Intra-peritoneal administration of the aqueous extract of O. ficus-indica flowers at the highest dose did not produce any toxicity symptoms, thus the median lethal dose (LD50) was estimated to be greater than 2,500 mg kg-1. The results of the pain behavior evaluation according to the gender approach of mice showed that the pain tolerance threshold is high in males compared to females. We found that various plant extracts at doses of 300, 500, and 1,000 mg kg-1 i.p., displayed significant and dose-dependent protective effects (p &lt; 0.01, p &lt; 0.001, and p &lt; 0.0001) as measured by increased latency time compared to vehicle control. The maximum anti-nociceptive effect was with the ethanol extract (71%) at 60 minutes at a dose of 1,000 mg kg-1, which was equivalent to the effect of morphine (70%). The results suggested that O. ficus-indica might possess significant analgesic effects, supporting the use of this plant in traditional medicine.

Investigation of pain sensitivity following 3 nights of disrupted sleep in healthy individuals.

Poor quality sleep is a common complaint among people with chronic pain. The co-occurrence of poor sleep quality and chronic pain often comes with increased pain intensity, more disability and a higher cost of healthcare. Poor sleep has been suggested to affect measures of peripheral and central pain mechanisms. To date, sleep provocations are the only models proven to affect measures of central pain mechanisms in healthy subjects. However, there are limited studies investigating the effect of several nights of sleep disruption on measures of central pain mechanisms. The current study implemented three nights of sleep disruption with three planned awakenings per night in 30 healthy subjects sleeping at home. Pain testing was conducted at the same time of day at baseline and follow-up for each subject. Pressure pain thresholds were assessed bilaterally on the infraspinatus and gastrocnemius muscles. Using handheld pressure algometry, suprathreshold pressure pain sensitivity and area were also investigated on the dominant infraspinatus muscle. Cuff-pressure pain detection and tolerance thresholds, temporal summation of pain and conditioned pain modulation were investigated using cuff-pressure algometry. Temporal summation of pain was significantly facilitated (p= 0.022), suprathreshold pain areas (p= 0.005) and intensities (p< 0.05) were significantly increased, and all pressure pain thresholds were decreased (p< 0.005) after sleep disruption compared to baseline. The current study found that three consecutive nights of sleep disruption at home induced pressure hyperalgesia and increased measures of pain facilitation in healthy subjects, which is consistent with previous findings. Poor quality of sleep is often experienced by patients with chronic pain, with the most common complaint being nightly awakenings. This exploratory study is the first to investigate changes in measures of central and peripheral pain sensitivity in healthy subjects after sleep disruptions for three consecutive nights without any restrictions on total sleep time. The findings suggest that disruptions to sleep continuity in healthy individuals can induce increased sensitivity to measures of central and peripheral pain sensitization.