Pain Threshold Tolerance Research Articles

Pre-treatment pain sensitivity is associated with outcome following exercise therapy in patients with knee osteoarthritis - an observational study

Purpose: Exercise therapy in combination with education is recommended as first-line treatment for painful knee osteoarthritis (KOA). In clinical practice, supervised exercise therapy and education demonstrate approx. 25% pain relief following an 8-week treatment program. Studies indicate that some patients with KOA experience larger pain relief compared to others. Assessments of peripheral and central pain mechanisms has been used to predict responders and non-responders to treatment. Studies on surgery and treatment with non-steroid anti-inflammatory drugs in patients with KOA have indicated that patients with higher levels of pain sensitivity might respond less positive. The primary aim of this observational study was to investigative if measures of pre-treatment pain sensitivity was associated with clinical outcomes after supervised exercise therapy and education. Methods: Patients with painful KOA (numeric rating scale [NRS, 0-10] ≥ 3) were included, and examined before and 1-2 weeks after 6-8 weeks of supervised exercise therapy (2 sessions of 1 hour per week) and 2 sessions of patient education. Handheld pressure pain threshold (PPT) was assessed locally at the most painful knee at 4 peripatellar sites (knee) and at two remote sites at the m. tibialis anterior (TA) and the contralateral m. extensor carpi radialis longus (ECRL). Further, computer-controlled cuff algometry at the lower leg with the most intense knee pain was used to assess pain detection threshold (cPDT), pain tolerance threshold (cPTT) and conditioned pain modulation (cCPM). Peak pain intensity within the last 24 hours (NRS, 0-10), PainDetect questionnaire (PDQ, 0-38) and Knee injury and Osteoarthritis Outcome Score (KOOS) were assessed as clinical measures. PDQ assesses the pain phenotype with a score ≤ 12 indicating probably nociceptive pain, 13-18 uncertain pain phenotype and ≥ 19 probably neuropathic pain. KOOS4 was defined as the average score of the subscale scores for Pain, Symptoms, Activity of Daily Living and Quality of Life (0-100 with 0 indicating extreme problems and 100 indicating no problems). Physical performance was assessed using the 40-meter walk test (40MWT). A treatment attendance score (%) was calculated for each patient by dividing the number of sessions attended by the number of sessions scheduled (twice per week). This study was approved by the local ethical committee (N-20190045) and pre-registered at clinicaltrials.org (NCT04123756). All participants gave oral and written informed consent prior to enrollment. Results: This interim analysis reports on the first patients recruited for this observational study. Eleven KOA patients (6 women) with mean peak pain intensity of 6.0 ± 1.5, median pain duration 17.0 months (range: 5-120) and body mass index of 30.3 ± 5.7 were included in this interim analysis. In one subject, follow-up was made by telephone due to the COVID-19 situation, leaving 10 subject for the analysis on changes in pain sensitivity measures. Attendance score was 98.1 ± 18.1% during 7.1 ± 0.7 weeks. Following treatment, improvements were observed in KOOS4 (57.1 ± 10.0 at baseline vs. 65.3 ± 13.1 at follow-up, P < 0.01), and peak pain intensity (6.0 ± 1.5 vs. 3.2 ± 2.3, P < 0.001). No differences were seen for PDQ (7.6 ± 2.6 vs 6.8 ± 3.6, P = 0.77) and 40MWT (27.1 ± 6.6 sec vs. 25.8 ± 5.2 sec, P = 0.29). Further, no changes in any of the pain sensitivity measures were found following treatment (all Ps > 0.15). Pre-treatment cPDT (rs < 0.73, P < 0.05) and cPTT (rs < 0.72, P < 0.05) were associated with post-treatment KOOS4. No significant associations were found between pre-treatment PPT or CPM effects and post-treatment peak pain measures or change in KOOS-4 (P > 0.05). Conclusions: These results indicate that patients with higher pre-treatment pressure pain sensitivity have worse KOOS4 scores following supervised exercise therapy and education.

Characteristics of Non-Ablative Resurfacing of Soft Tissues by Repetitive Er:YAG Laser Pulse Irradiation.

Background and ObjectivesRecently, several minimally invasive gynecological, ENT and esthetic procedures have been introduced that are based on delivering “smooth” sequences of Er:YAG laser pulses to cutaneous or mucosal tissue at moderate cumulative fluences that are not only below the ablation threshold but typically also do not require local anesthesia. To explain the observed clinical results using “smooth‐resurfacing,” it has been suggested that in addition to the direct heat injury to deeper‐lying connective tissues, there is an additional mechanism based on indirect triggering of tissue regeneration through short‐exposure, intense heat shocking of epithelia. The goal of this study is to improve understanding of the complex dynamics of the exposure of tissues to a series of short Er:YAG laser pulses, during which the thermal exposure times transition from extremely short to long durations.Study Design/Materials and MethodsA physical model of laser‐tissue interaction was used to calculate the temperature evolution at the irradiated surface and deeper within the tissue, in combination with a chemical model of tissue response based on the recently introduced variable heat shock (VHS) model, which assumes that the tissue damage represents a combined effect of two limiting Arrhenius′ processes, defining cell viability at extremely long and short exposure times. Superficial tissue temperature evolution was measured during smooth‐resurfacing of cutaneous and mucosal tissue, and compared with the model. Two modalities of non‐ablative resurfacing were explored: a standard “sub‐resurfacing” modality with cumulative fluences near the ablation threshold, and the “smooth‐resurfacing” modality with fluences below the patient′s pain threshold. An exemplary skin tightening clinical situation was explored by measuring pain tolerance threshold fluences for treatments on abdominal skin with and without topical anesthesia. The obtained temperature data and pain thresholds were then used to study the influence of Er:YAG laser sequence parameters on the superficial (triggering) and deep (coagulative) tissue response.ResultsThe simulations show that for the sub‐resurfacing modality, the parameter range where no excessive damage to the tissue will occur is very narrow. On the other hand, using pain tolerance as an indicator, the smooth‐resurfacing treatments can be performed more safely and without sacrificing the treatment efficacy. Two preferred smooth‐resurfacing treatment modalities were identified. One involves using optimally long pulse sequence durations (≈1–3 seconds) with an optimal number of pulses (N ≈ 10–30), resulting in a maximal short‐exposure superficial tissue response and moderate coagulation depths. And for deeper coagulation, without significant superficial heat shocking, very long pulse sequences (>5 seconds) with a large number of delivered pulses are to be used in combination with topical anesthesia.ConclusionsA comparison of the simulations with the established smooth‐resurfacing clinical protocols in gynecology, ENT, and esthetics suggests that, through clinical experience, the clinical protocols have been optimized for the maximal superficial heat shock triggering effect. Further research is needed to gain a better understanding of the proposed role of heat shock triggering in the clinically observed regeneration of cutaneous, vaginal, and oral tissues following Er:YAG laser smooth‐resurfacing. Lasers Surg. Med. © 2021 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC.

Ictal and interictal brain activation in episodic migraine: Neural basis for extent of allodynia.

In some patients, migraine attacks are associated with symptoms of allodynia which can be localized (cephalic) or generalized (extracephalic). Using functional neuroimaging and cutaneous thermal stimulation, we aimed to investigate the differences in brain activation of patients with episodic migraine (n = 19) based on their allodynic status defined by changes between ictal and interictal pain tolerance threshold for each subject at the time of imaging. In this prospective imaging study, differences were found in brain activity between the ictal and interictal visits in the brainstem/pons, thalamus, insula, cerebellum and cingulate cortex. Significant differences were also observed in the pattern of activation along the trigeminal pathway to noxious heat stimuli in no allodynia vs. generalized allodynia in the thalamus and the trigeminal nucleus but there were no activation differences in the trigeminal ganglion. The functional magnetic resonance imaging (fMRI) findings provide direct evidence for the view that in migraine patients who are allodynic during the ictal phase of their attacks, the spinal trigeminal nucleus and posterior thalamus become hyper-responsive (sensitized)–to the extent that they mediate cephalic and extracephalic allodynia, respectively. In addition, descending analgesic systems seem as “switched off” in generalized allodynia.

Immediate effect of quick massage on muscle tension and pressure pain threshold

ABSTRACT BACKGROUND AND OBJECTIVES: Massage is described as an effective complementary therapy for relieving muscle tension and pain. The aim of this study was to verify the benefits of quick massage on muscle tension and pressure pain tolerance threshold (PPT). METHODS: A randomized clinical study in which 40 professors participated and were randomly divided into control (CG) and experimental (EG) groups. They were assessed for the level of muscle tension in the shoulder and neck regions using the visual analogue scale (VAS). PPT was assessed through algometry at the upper trapezius and sternocleidomastoid muscles and at the following anatomical areas: base of the occipital, scapular spine, thoracic (T6-T7) and lumbar (L4-L5) regions. The EG received a single session of quick massage for 20 minutes on the shoulders, neck and spine. RESULTS: Regarding pain, a significant difference was observed only at the base of the occipital, the EG presented greater tolerance to pressure pain both before and after the intervention when compared to the CG. Regarding muscle tension, after the intervention, there was a reduction in the perception in the EG compared to the CG group. CONCLUSION: Quick massage was efficient to decrease the perception of muscle tension assessed by VAS, however, PPT did not increase after the intervention.

The role of serotonin in the control of esophageal sensitivity assessed by multimodal stimulation in health.

Esophageal hypersensitivity is considered an important pathophysiological mechanism in refractory gastroesophageal reflux disease (GERD) patients. Serotonin (5-HT) plays an important role in the regulation of GI (gastrointestinal) secretion, motility and sensitivity. Previous studies found that altered 5-HT availability has no clear effects on esophageal/GI sensations. Our aim was therefore to investigate the role of 5-HT in esophageal sensitivity in healthy volunteers (HV). Esophageal sensitivity to thermal, mechanical, electrical, and chemical stimuli was assessed in 3 different placebo-controlled studies. In the first study, the effect of citalopram (40mg; 5-HT reuptake inhibitor; intravenous) was investigated (n=14). In the second study, the effect of buspirone (20mg; 5HT1A agonist; oral) was investigated (n=10). In the third study, acute tryptophan depletion (ATD) was used to decrease 5-HT levels to investigate the effect of reduced 5-HT availability on esophageal sensitivity (n=15). No difference was observed in esophageal sensitivity after the administration of citalopram or buspirone (all p>0.06). In contrast, pain perception threshold to chemical stimulation was increased after ATD (p=0.017, Cohen's d+=0.67). No effect was found on the first perception or pain tolerance threshold. ATD had no influence on esophageal sensitivity to thermal, mechanical, and electrical stimulation compared with placebo. ATD, which induces 5-HT depletion, significantly decreased pain perception threshold during chemical stimulation, without affecting sensitivity to mechanical, thermal, or electrical stimulation. These findings confirm the involvement of 5-HT in the control of esophageal acid sensitivity, but identifying the receptors involved requires more ligands and studies.

Pain and Cortisol in Patients with Fibromyalgia: Systematic Review and Meta-Analysis.

This systematic review and meta-analysis sought to gain further insight into the relationship between cortisol reactivity and chronic widespread pain in patients with fibromyalgia. The studies selected were those conducted in adults with fibromyalgia that were random controlled, non-controlled or observational. Studies were excluded if they examined diseases other than fibromyalgia or if they did not report on pain or cortisol. Twelve studies met inclusion criteria. Data were extracted into tabular format using predefined data fields by two reviewers and assessed for accuracy by a third reviewer. The methodological quality of the studies was assessed using the PEDro scale. Data Synthesis: Of 263 studies identified, 12 were selected for our review and 10 were finally included as their methodological quality was good. In the meta-analysis, we calculated effect sizes of interventions on pain indicators and cortisol levels in patients with fibromyalgia. A small overall effect of all the interventions was observed on pain tolerance and pressure pain thresholds, yet this effect lacked significance (ES = 0.150; 95%CI 0.932–1.550; p > 0.05). Conclusions: While some effects of individual nonpharmacological therapeutic interventions were observed on both cortisol levels and measures of pain, our results suggest much further work is needed to elucidate the true relationship between chronic widespread pain and cortisol levels in patients with fibromyalgia.

Comparison of the effect of two different types of dry-needling techniques on subacromial impingement syndrome

IntroductionInfraspinatus is one of the main muscles that is involved in the subacromial impingement syndrome. Dry needling and routine physical therapy can improve this syndrome. However, the dry needling technique is not well defined. Designrandomized controlled clinical trial, single-blind study. MethodSixty-six patients diagnosed with shoulder impingement syndrome were recruited and randomly divided into three groups. InterventionsIn 1st group; patients received deep dry needling technique in addition to routine physical therapy, in Hong's group; patients received Hong's dry needling technique in addition to routine physiotherapy and in third group; patient just received routine physical therapy. Main outcome measure(s)Before, immediately after and 4 weeks after the intervention, pain, disability and the pressure pain threshold were measured. ResultsThe findings of this study indicated that in DDN group, pain and disability reduction was significantly more than two other groups. Although, the pressure pain tolerance increased in all three groups after treatment, but the increase between groups was not significantly different. All study groups showed reduction in pain, while there was no significant difference between the three groups. ConclusionPain and disability reduction in the DDN group compared to the other two groups may reveal the treatment with deep dry needling technique along with routine physiotherapy is more effective than receiving dry needling with Hong's technique or routine physiotherapy alone. However, there was no significant difference between the three groups in pressure pain tolerance threshold and pain reduction.

Repeated Injections of Low-Dose Nerve Growth Factor (NGF) in Healthy Humans Maintain Muscle Pain and Facilitate Ischemic Contraction-Evoked Pain.

Nerve growth factor (NGF) is essential for generating and potentiating pain responses. This double-blinded crossover study assessed NGF-evoked pain in healthy humans after repeated NGF injections in the tibialis anterior (TA) muscle compared with control injections of isotonic saline. Twenty healthy subjects participated in two experimental phases; each consisted of seven sessions over 21 days. At day0, day2, and day4, a low-dose NGF (1µg) was injected. Data on daily self-reported muscle pain (using a Likert scale) were collected. Data on pressure pain thresholds (PPTs), pain evoked by nonischemic and ischemic muscle contractions (using a numerical rating scale [NRS]), pressure pain detection (PDT), and pain tolerance thresholds (PTTs) to cuff algometry were recorded before day0 and at 1, 2, 4, 7, 10, and 21days after the first injection. Temporal summation of pain (TSP) and conditioned pain modulation (CPM) were recorded to assess central pain mechanisms. Likert scores remained elevated for 9days after NGF injection (P<0.05). PPTs at the TA muscle were decreased at day1 until day7 after NGF injection compared with day0 (P=0.05). In subjects presenting with NGF-induced muscle hyperalgesia, pain NRS scores evoked by nonischemic contractions were higher after NGF injection at day4 and day7 (P<0.04) compared with the control condition. At all time points, higher pain NRS scores were found with ischemic compared with nonischemic contractions (P<0.05). The pain NRS after ischemic contractions was elevated following prolonged NGF hyperalgesia at day7 compared with the control condition and day0 (P<0.04). The PDT, PTT, TSP, and CPM remained unchanged during the period of NGF-induced hyperalgesia. Repeated low-dose NGF injections maintain muscle pain and potentiate pain evoked by ischemic contractions during prolonged NGF hyperalgesia.

Motivational nondirective resonance breathing versus transcutaneous vagus nerve stimulation in the treatment of fibromyalgia: study protocol for a randomized controlled trial

BackgroundChronic widespread pain (CWP), including fibromyalgia (FM), affects one in every ten adults and is one of the leading causes of sick leave and emotional distress. Due to an unclear etiology and a complex pathophysiology, FM is a condition with few, if any, effective and safe treatments. However, current research within the field of vagal nerve innervation suggests psychophysiological and electrical means by which FM may be treated. This study will investigate the efficacy of two different noninvasive vagal nerve stimulation techniques for the treatment of FM.MethodsThe study will use a randomized, single-blind, sham-controlled design to investigate the treatment efficacy of motivational nondirective resonance breathing (MNRB™) and transcutaneous vagus nerve stimulation (Nemos® tVNS) on patients diagnosed with FM. Consenting FM patients (N = 112) who are referred to the Department of Pain Management and Research at Oslo University Hospital, in Oslo, Norway, will be randomized into one of four independent groups. Half of these participants (N = 56) will be randomized to either an experimental tVNS group or a sham tVNS group. The other half (N = 56) will be randomized to either an experimental MNRB group or a sham MNRB group. Both active and sham treatment interventions will be delivered twice per day at home, 15 min/morning and 15 min/evening, for a total duration of 2 weeks (14 days). Participants are invited to the clinic twice, once for pre- and once for post-intervention data collection. The primary outcome is changes in photoplethysmography-measured heart rate variability. Secondary outcomes include self-reported pain intensity on a numeric rating scale, changes in pain detection threshold, pain tolerance threshold, and pressure pain limit determined by computerized pressure cuff algometry, blood pressure, and health-related quality of life.DiscussionThe described randomized controlled trial aims to compare the efficacy of two vagal nerve innervation interventions, MNRB and tVNS, on heart rate variability and pain intensity in patients suffering from FM. This project tests a new and potentially effective means of treating a major public and global health concern where prevalence is high, disability is severe, and treatment options are limited.Trial registrationClinicalTrials.govNCT03180554. Registered on August 06, 2017.

Dissociation of Endogenous Pain Inhibition Due to Conditioned Pain Modulation and Placebo in Male Athletes Versus Nonathletes.

Animals and humans are able to inhibit pain by activating their endogenous pain-inhibition system. Endurance athletes possess a higher pain-tolerance threshold and a greater conditioned pain modulation (CPM) effect than nonathletes, suggesting better endogenous pain inhibition. In addition to CPM, placebo is another prominent paradigm used to test endogenous pain inhibition. However, whether the placebo effect and the CPM effect share the same mechanisms of pain inhibition has not been investigated. If there is a shared mechanism, then endurance athletes should show not only a better CPM effect than nonathletes but also a greater placebo effect. Here, we investigated 16 male endurance athletes and 17 male nonathletes in well-established placebo and CPM paradigms to assess whether endurance athletes have a better endogenous pain-inhibition system than nonathletes. As expected, we find a significantly greater CPM effect in athletes than in nonathletes. In contrast, we could only find a significant placebo effect in nonathletes. Explorative analyses reveal negative associations between the placebo effect and heart rate variability as well as between the placebo effect and interoceptive awareness. Together, the results demonstrate a dissociation of endogenous pain inhibition of CPM and placebo effect between endurance athletes and nonathletes. This suggests that both effects are based, at least in part, on different biological mechanisms.

Pain in the default mode network: a voxel-based morphometry study on thermal pain sensitivity.

During nociceptive processing of pain, activated regions, specified as the 'pain matrix', have been proven not selectively or preferentially tied to pain. Counterintuitively, the deactivated regions, especially the default mode network (DMN), are recently revealed to be simultaneously and functionally involved. In this study, we searched for pain-specific structural correlates among pain-free young adults using the voxel-based morphometry (VBM) approach within regions of interest comprising the pain matrix and DMN. Variances in confounding factors, namely the thermal detection threshold, thermal pain tolerance threshold and pain-related psychological traits, were statistically controlled to obtain pain-specific structural correlates. As a result, we found that less grey matter volume (GMV) of a critical DMN region, the precuneus, predicts enhanced thermal pain sensitivity (i.e., lower threshold). In contrast, this relationship is absent in all regions within the pain matrix. Such a dissociation between pain matrix and precuneus highlights the significance of precuneus in processing of pain, and is discussed with a conception taking pain as a salience detection system for the body, rather than as a nociceptive-specific system restricted within the so-called pain matrix.

Translation, Cross-Cultural Adaptation, and Validation of the Pain Sensitivity Questionnaire in Dutch Healthy Volunteers.

An increased sensitivity to painful stimuli has been proposed to be related to the development of chronic pain. Therefore, assessment of individual pain sensitivity is useful in clinical practice. However, experimental pain testing may be uncomfortable for patients and requires specific equipment. The Pain Sensitivity Questionnaire (PSQ) has been developed to facilitate assessment of pain sensitivity. In this study, we aimed to translate and cross-culturally adapt the PSQ from its published German and English versions into the Dutch language and to assess validity of the PSQ in healthy volunteers. After translation and cross-cultural adaptation of the PSQ following international guidelines, we validated the PSQ in 394 healthy volunteers by comparing the PSQ-values with two different experimental pain tests: electrical pain tolerance (EPT) and pressure pain threshold (PPT). In addition, ratings of pain intensity during these tests were obtained on the numerical rating scale (NRS, 0–10). We found that the reliability of the PSQ based on internal consistency was good (Cronbach's alpha 0.90). PSQ-scores, adjusted for age and sex, were statistically significant and weakly inversely correlated to EPT (PSQ-moderate: rho = −0.24, p=0.007; PSQ-total: rho = −0.22, p=0.016). No statistically significant correlation between PSQ-scores and PPT was found. Concerning the pain scores, PSQ-scores were weakly to moderately correlated to EPT-NRS (PSQ-minor: rho = 0.21, p=0.021; PSQ-moderate: rho = 0.22, p=0.016; PSQ-total: rho = 0.23, p=0.009) as well as PPT-NRS (PSQ-minor: rho = 0.32, p < 0.001; PSQ-moderate: rho = 0.36, p < 0.001; PSQ-total: rho = 0.37, p < 0.001). Therefore, we concluded that the Dutch version of the PSQ is culturally appropriate for assessing self-reported pain sensitivity in healthy volunteers.

The efficacy of mindfulness-based interventions in acute pain: a systematic review and meta-analysis.

Recent meta-analyses have shown mindfulness-based interventions (MBIs) to be effective for chronic pain, but no pooled estimates of the effect of MBIs on acute pain are available. This meta-analysis was conducted to fill that gap. A literature search was conducted in 4 databases. Articles were eligible if they reported on randomized controlled trials of MBIs for people with acute pain and one of the following outcomes: pain severity, pain threshold, pain tolerance, or pain-related distress. Two authors independently extracted the data, assessed risk of bias, and provided GRADE ratings. Twenty-two studies were included. There was no evidence of an effect of MBIs on the primary outcome of pain severity in clinical {Hedges' g = 0.52; (95% confidence interval [CI] -0.241 to 1.280)} or experimental settings (Hedges' g = 0.04; 95% CI [-0.161 to 0.247]). There was a beneficial effect of MBIs on pain tolerance (Hedges' g = 0.68; 95% CI [0.157-1.282]) and pain threshold (Hedges' g = 0.72; 95% CI [0.210-1.154]) in experimental studies. There was no evidence of an effect of MBIs compared to control for pain-related distress in clinical (Hedges' g = 0.16; 95% CI [-0.018 to 0.419]) or experimental settings (Hedges' g = 0.44; 95% CI [-0.164 to 0.419]). GRADE assessment indicated that except for pain tolerance, the data were of low or very low quality. There is moderate evidence that MBIs are efficacious in increasing pain tolerance and weak evidence for pain threshold. However, there is an absence of good-quality evidence for the efficacy of MBIs for reducing the pain severity or pain-related distress in either clinical or experimental settings.

Activation of the descending pain modulatory system using cuff pressure algometry: Back translation from man to rat.

Diffuse noxious inhibitory controls (DNIC) as measured in rat and conditioned pain modulation (CPM), the supposed psychophysical paradigm of DNIC measured in humans, are unique manifestations of an endogenous descending modulatory pathway that is activated by the application of a noxious conditioning stimulus. The predictive value of the human CPM processing is crucial when deliberating the translational worth of the two phenomena. For CPM or DNIC measurement, test and conditioning stimuli were delivered using a computer-controlled cuff algometry system or manual inflation of neonate blood pressure cuffs, respectively. In humans (n=20), cuff pain intensity (for pain detection and pain tolerance thresholds) was measured using an electronic visual analogue scale. In isoflurane-anaesthetized naïve rats, nociception was measured by recording deep dorsal horn wide dynamic range (WDR) neuronal firing rates (n=7) using in vivo electrophysiology. A painful cuff-pressure conditioning stimulus on the leg increased pain detection and pain tolerance thresholds recorded by cuff stimulation on the contralateral leg in humans by 32%±3% and 24%±2% (mean±SEM) of baseline responses, respectively (p<.001). This finding was back-translated by revealing that a comparable cuff-pressure conditioning stimulus (40kPa) on the hind paw inhibited the responses of WDR neurons to noxious contralateral cuff test stimulation to 42%±9% of the baseline neuronal response (p=.003). These data substantiate that the noxious cuff pressure paradigm activates the descending pain modulatory system in rodent (DNIC) and man (CPM), respectively. Future back and forward translational studies using cuff pressure algometry may reveal novel mechanisms in varied chronic pain states. This study provides novel evidence that a comparable noxious cuff pressure paradigm activates a unique form of endogenous inhibitory control in healthy rat and man. This has important implications for the forward translation of bench and experimental pain research findings to the clinical domain. If translatable mechanisms underlying dysfunctional endogenous inhibitory descending pathway expression (previously evidenced in painful states in rat and man) were revealed using cuff pressure algometry, the identification of new analgesic targets could be expedited.

Sensibilidad y dolor en distonías focales de la mano

IntroductionA growing body of evidence highlights the importance of understanding both the sensory and the motor pathophysiology of focal dystonia in order to improve its treatment. This study aims to evaluate somatosensory afferences in patients with focal or segmental dystonia affecting the upper limbs, to analyse whether the dominant limb is more frequently affected, to analyse pain tolerance, and to examine the potential association with pain perception in patients with hand dystonia. MethodsWe recruited 24 participants: 12 patients with focal hand dystonia and 12 individuals without dystonia. All participants were evaluated with a digital algometer (Somedic SenseLab AB®, Farsta, Sweden), a Semmes-Weinstein monofilament test, and the visual analogue scale for pain. ResultsAccording to our data, patients showed greater impairment in surface sensitivity than controls, both in the dominant and the non-dominant hands, as well as greater presence of pain (P>.001). Furthermore, the dystonia group showed a negative correlation between perceived pain and pressure pain tolerance threshold (rho=−0.83; P<.001). ConclusionsPatients with focal hand dystonia presented alterations in sensitivity and more severe perceived pain than individuals without dystonia. Future studies with larger samples should aim to analyse the clinical implications and everyday impact of both objective and subjective pain.

Effect of ADRA2A gene polymorphisms on the anesthetic and analgesic effects of dexmedetomidine in Chinese Han women with cesarean section.

It is well known that differences in drug reactions among individuals are widespread, and therefore the study of genetic polymorphisms of drug targets has become a research hotspot. Dexmedetomidine is clinically effective by acting on α2 adrenergic receptor and the impact of the adrenoceptor α2A gene (ADRA2A) polymorphisms on the anesthetic and analgesic effects of dexmedetomidine is related to the clinical application of dexmedetomidine. The present study aimed to analyze the effects of the rs1800035, rs201376588 and rs775887911 locus single-nucleotide polymorphisms of the ADRA2A on the anesthetic and analgesic effects of dexmedetomidine in Chinese Han women. A total of 434 Chinese women undergoing cesarean section were enrolled in this study. A 3-ml fasting venous blood sample was collected from all subjects for genomic DNA extraction and genotype detection. The pre-anesthetic and post-anesthetic pain threshold (PTh), pain tolerance threshold (PTTh), mean arterial pressure, heart rate, blood oxygen saturation, cortisol (Cor) content, blood glucose (Glu) content, opioid usage, patient-controlled analgesia pressing times, surgical satisfaction and postoperative adverse reactions were recorded. The visual analogue scale (VAS) and Ramsay sedation score were evaluated. PTh and PTTh in the wild-type women were higher than those in the women with mutations (P<0.05). The postoperative VAS scores of wild-type women were lower than those of mutants (P<0.05). The Ramsay sedation scores of wild-type patients at 12 h after the operation were significantly higher than in those with mutations (P<0.05). The levels of Cor and Glu in women with mutations were significantly higher than those of wild-type women at 12, 24 and 48 h after surgery (P<0.05). The satisfaction with surgery of wild-type patients was higher than that of patients with mutations (P<0.05). Gene mutations of rs1800035, rs201376588 and rs775887911 loci in the ADRA2A gene reduced the anesthetic and analgesic effect during and after cesarean section in Chinese Han women. Postoperative analgesia of mothers with mutations may require higher doses of analgesics.

5'UTR polymorphism in the serotonergic receptor HTR3A gene is differently associated with striatal Dopamine D2/D3 receptor availability in the right putamen in Fibromyalgia patients and healthy controls-Preliminary evidence.

Extensive literature has investigated the role of serotonin (5-HT) in the control of the central dopamine (DA) systems, and their dysfunction in the pathological conditions. 5-HT stimulates the local DA release in striatal regions via activation of various receptors including serotonin receptor-3 (5-HT3). Several studies have related polymorphisms (SNPs) in the serotonin receptor-3 (HTR3) genes to be associated with the pain modulation and endogenous pain suppression. A few studies suggested a functional role of 5'UTR SNP in the serotonergic receptor HTR3A gene (rs1062613) in the development of the chronic pain and Fibromyalgia syndrome (FMS) in particular. Here, we investigated the effect of a 5'UTR SNP in the serotonergic receptor HTR3A gene (rs1062613) on striatal dopamine D2/D3 receptor (DRD2) availability and reward-associated DA release in response to unpredictable monetary rewards in 23 women with FMS and 17 age-matched healthy female controls. Furthermore, we aimed to examine if SNP rs1062613 is associated with thermal pain and pain tolerance thresholds. We used PET and [11 C]raclopride to assess the DRD2 availability. In the same participants we used the [11 C]raclopride PET bolus-plus-infusion method to measure the [11 C]raclopride receptor binding potential (ΔBP) between an unpredictable reward condition and a sensorimotor control condition. DRD2 availability and ΔBP were assessed in MRI-based striatal regions of interest. Thermal pain and pain tolerance thresholds were assessed outside the scanner. The frequency of SNP rs1062613 genotype differed significantly between groups, indicating that CC homozygotes were more frequent in FMS patients (82.6%) than in healthy controls (41.3%). Our results showed a significant main effect of SNP rs1062613 on [11 C]raclopride binding potential in the right caudate nucleus indicating a higher DRD2 receptor availability for CC-genotype of this SNP. Furthermore, we found a significant group × SNP interaction on [11 C]raclopride binding potential in the right putamen, indicating a higher DRD2 availability in T-carriers compared to CC genotype of SNP rs1062613 in FMS patients, whereas this effect was not present in healthy controls. However, we did not find an influence of SNP rs1062613 on reward-related DA release. In addition, there was no association between SNP rs1062613 and pain threshold or pain tolerance threshold in our data. These preliminary results indicate that SNP rs1062613 in the serotonergic receptor HTR3A gene possibly modulates the DRD2 receptor availability.

COMT gene variants and β-endorphin levels contribute to ethnic differences in experimental pain sensitivity.

This cross-sectional study investigated whether the catechol-O-methyltransferase (COMT) gene acts as a significant regulator of pain signaling pathways, regulates β-endorphin, and contributes to ethnic differences in pain sensitivity. One-hundred-sixty healthy subjects were enrolled in this study, with Han and Uyghur groups each consisting of 80 participants. Subjects went through six pain threshold experiments. From venous blood, COMT polymorphisms were genotyped, and serum β-endorphin levels were measured. Bivariate correlation analysis and multiple linear regression were used to identify the relationships among genotypes or β-endorphin levels and different types of pain thresholds. Han and Uyghur ethnic differences were determined in terms of acute-pressure pain-perception thresholds, blunt-pressure pain-perception thresholds, blunt-pressure pain-tolerance thresholds, electric pain-tolerance thresholds, β-endorphin levels, and distributions of rs4680 and rs4633 COMT polymorphisms. β-endorphin levels did not correlate with COMT rs4680 or rs4633 genotypes in both Han and Uyghur. Statistical predictors for a lower pain-threshold performance included being young, Uyghur, female, and having a low body mass index, low β-endorphin level, and the rs4680 GA or GG allele. There is the significant difference in pain sensitivity between healthy Han and Uyghur. COMT gene variants and β-endorphin levels contribute to ethnic differences in pain sensitivity.

Pain, disability and catastrophizing in individuals with knee osteoarthritis

ABSTRACT BACKGROUND AND OBJECTIVES: Knee osteoarthritis is among the leading sources of chronic disability and may lead to depression, anxiety and pain catastrophizing, enhancing perceived pain. This study aimed at investigating the influence of pain catastrophizing on attitudes and perception of pain, and in the functionality of individuals with knee osteoarthritis. METHODS: This observational study involved 18 patients, who were assessed for weight and height, and completed the Pain-related Catastrophizing Thoughts Scale (PCTS), Survey of Pain Attitudes (SPA), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the visual analog scale (VAS). Symptoms and disability were assessed by the Lequesne Index, functional mobility was evaluated by the Timed Up and Go (TUG) test. Pressure pain tolerance thresholds (PPT) were assessed by a digital algometer. RESULTS: Mean body mass index of the sample was classified as obese (32,2±4,3). When split by the median of PCTS, differences were observed in most domains of SPA. Patients with more catastrophic thoughts took longer to perform TUG and presented more pain, joint stiffness and worse functionality (WOMAC). Despite the tendency to report more pain (VAS) in patients above the median score of PCTS, no differences were observed between groups with higher or lower catastrophizing regarding PPT. Positive and significant associations between the Rumination factor of PCTS and WOMAC outcomes were observed, as well as between the Hopelessness factor and TUG, Lequesne and WOMAC. CONCLUSION: The higher the presence of catastrophic thoughts, the worse the attitudes towards pain and the physical functionality of knee osteoarthritis patients.

Effects of cold versus hot compress on pain in university students with primary dysmenorrhea

BACKGROUND AND OBJECTIVES: Dysmenorrhea is the most common gynecological complaint among young women. Several therapeutic resources have been studied, aiming at reducing pain. The objective of this study was to identify the influence of cold or hot compresses on pain intensity and pressure pain tolerance thresholds in women with primary dysmenorrhea. METHODS: A single-blind randomized clinical study involving 40 young women divided into two groups: hot compress or cold compress, applied for 20 minutes on the lower abdomen and lower back regions. Pressure pain tolerance thresholds were evaluated by algometry in the vastus medialis, gluteus maximus, lumbar paravertebral muscles and supraspinatus ligaments L4-L5 and L5-S1. Pain intensity was assessed by the visual analog scale. RESULTS: No significant changes in pressure pain tolerance thresholds were observed immediately after the application of the compresses, nor 30 minutes later. The comparison of the variation in the effect of changes showed no differences between the intervention groups, either regarding the pressure pain tolerance thresholds or the visual analog scale. However, both groups had a significant reduction in the visual analog scale right after the application and 30 minutes after the end of the intervention. Nevertheless, right after the use of the compresses, as well as 30 minutes after its end, the group that received the cold compress had a more significant reduction in pain intensity (p=0.002 and p=0.004, respectively). CONCLUSION: Cold or hot compresses did not produce changes in pressure pain tolerance thresholds. However, pain perception was lower after this treatment, especially in the group using cold compresses.