Pain Biomarkers Research Articles

Abstract 15587: Combined Spontaneous Coronary Artery Dissection and Takotsubo Cardiomyopathy in a Patient With Chest Pain

Introduction: Spontaneous coronary artery dissection (SCAD) and Takotsubo cardiomyopathy (TCM) are uncommon non-atherosclerotic causes of acute myocardial infarction (MI). These patients have fewer cardiovascular risk factors than those who have atherosclerotic MI. Clinical presentation in both subsets of MI is identical due to which diagnosis requires echocardiography and coronary angiography. The incidence of TCM and SCAD in the same patient is scarce and only documented in a few case reports and a case series. Case presentation: We present the case of a 50-year-old female with a past medical history of hypertension, hypothyroidism, and median arcuate ligament syndrome. She presented to the emergency department with intermittent chest pain radiating to her upper back, both arms, and her left jaw and it was associated with nausea. On examination, she was tachycardic, tachypneic, and anxious. She had normal heart sounds with no chest tenderness. Her EKG demonstrated ST-elevations in leads II, III, aVF, V4, V5, and V6. Laboratory results showed elevated high sensitivity troponin of 11,949 (pg/ml) and 30,256 (pg/ml) four hours later. The patient underwent emergent coronary angiography, which revealed diffuse tubular stenosis suggestive of type 2 SCAD in the second obtuse marginal artery but otherwise normal coronary anatomy with minimal stenosis. Left ventriculogram showed antero-apical, apical, and infero-apical hypokinesis and basal hyperkinesis, suggestive of Takotsubo cardiomyopathy. Transthoracic echocardiogram (TTE) completed 48 hours later demonstrated improved contractility with lateral wall hypokinesis. The patient was managed conservatively with medical management, and she was discharged on aspirin, plavix, carvedilol, isosorbide mononitrate, and losartan. Conclusions: SCAD and TCM are uncommon diagnoses that can rarely co-exist. TTE can help diagnose TCM in patients with chest pain and elevated cardiac biomarkers. Non-occlusive coronary vasculature is a diagnostic criterion per the proposed Mayo Clinic criteria. This case highlights the importance of coronary angiography in patients with TCM for assessment of potential co-existent coronary vascular pathology; SCAD in our case.

Biomarkers for Chronic Pain: Significance and Summary of Recent Advances.

Chronic pain can be difficult to predict and a challenge to treat. Biomarkers for chronic pain signal an opportunity for advancements in both management and prevention, and through their research and development offer new insights into the complex processes at play. This review considers the latest research in chronic pain biomarker development and considers how close we are to bringing these from bench to bedside. While some headway has been made that offers efficiencies in patient selection, it is unlikely that a single test will encompass the variety of chronic pain phenotypes. We offer some insights for the near future in biomarker development and areas of continued unmet need.

A Novel Constraint-Based Knee- Guided Neuroevolutionary Algorithm for Context-Specific ECG Early Classification.

Cardiovascular diseases (CVDs) are considered the greatest threat to human life according to World Health Organization. Early classification of CVDs and the appropriate follow-up treatment are crucial for preventing sudden deaths. Electrocardiogram (ECG) is one of the most common non-invasive tools used to evaluate the state of the heart, which can be exploited to automatically diagnose as well. However, the importance of diagnosing CVDs is varying in different context-specific scenarios. For example, ST-segment elevation (STE) is an acute myocardial infarction indicator for patients associated with chest pain and cardiac biomarker. In in-hospital healthcare, STE should be diagnosed with a higher priority than the other phenotypes of ECG. Hence, the context-specific requirements should be considered in ECG early classification problems. We formalize the ECG early classification problem as the context-specific time series classification problem. We propose a novel Constraint-based Knee-guided Neuroevolutionary Algorithm (CKNA) based on the Snippet Policy Networks V2 to solve this problem. To validate the proposed method, we perform a series of experiments on two public ECG datasets under various context-specific simulated scenarios after consulting with physicians specializing in the area. Experimental results show that CKNA significantly improves the average recall of disease classification by 5.5% compared to the competing baseline under user-specified requirements. Moreover, experimental results prove that CKNA presents a feasible solution for the early classifying of cardiac arrhythmias under different user-specified scenarios.

Monoaminergic mediation of hyperalgesic and analgesic descending control of nociception in mice.

Descending control of nociception (DCN; also known as conditioned pain modulation [CPM], the behavioral correlate of diffuse noxious inhibitory controls) is the phenomenon whereby pain inhibits pain in another part of the body and is the subject of increasing study because it may represent a biomarker of chronic pain. We recently discovered that pain modulation on the application of a DCN paradigm involving low-intensity test stimuli occurs in the direction of hyperalgesia in healthy mice and rats, whereas the use of high-intensity stimuli produces analgesia. To elucidate the physiological mechanisms underlying hyperalgesic DCN, we administered agonists and antagonists of norepinephrine (NE) and serotonin (5-HT) receptors, key neurochemical players in the production of analgesic DCN. We find that 3 different monoamine reuptake inhibitors-the NE-selective reboxetine, the 5-HT-selective fluoxetine, and the dual NE/5-HT agonist duloxetine-all abolish hyperalgesic DCN when administered into the spinal cord (but not systemically), with no effect on heat or mechanical pain sensitivity. The reversal by reboxetine of hyperalgesic DCN is mediated by α 2 -adrenergic receptors (ie, blocked by atipamezole), and the fluoxetine reversal is mediated by 5-HT 7 receptors (ie, blocked by SB269970). By contrast, analgesic DCN was found to be reversed by atipamezole and SB269970 themselves, with no effect of reboxetine or fluoxetine. Thus, hyperalgesic DCN seems to be the neurochemical opposite to analgesic DCN. These data further validate and help elucidate a preclinical paradigm that mimics dysfunctional CPM and thus may form the basis of translational experiments that aim to reveal preventative pharmacological strategies for individuals predisposed to persistent pain.

Recent updates in the treatment of diabetic polyneuropathy.

Distal symmetric diabetic peripheral polyneuropathy (DPN) is the most common form of neuropathy in the world, affecting 30 to 50% of diabetic individuals and resulting in significant morbidity and socioeconomic costs. This review summarizes updates in the diagnosis and management of DPN. Recently updated clinical criteria facilitate bedside diagnosis, and a number of new technologies are being explored for diagnostic confirmation in specific settings and for use as surrogate measures in clinical trials. Evolving literature indicates that distinct but overlapping mechanisms underlie neuropathy in type 1 versus type 2 diabetes, and there is a growing focus on the role of metabolic factors in the development and progression of DPN. Exercise-based lifestyle interventions have shown therapeutic promise. A variety of potential disease-modifying and symptomatic therapies are in development. Innovations in clinical trial design include the incorporation of detailed pain phenotyping and biomarkers for central sensitization.

Different Profiles of the Triad of Lysophosphatidylcholine, Lysophosphatidic Acid, and Autotaxin in Patients with Neuropathic Pain Diseases: a Preliminary Observational Study.

The mechanisms underlying neuropathic pain remain unclear. Lysophosphatidic acid (LPA) is a bioactive phospholipid derived mainly from lysophosphatidylcholine (LPC) by extracellular autotaxin (ATX), and has attracted attention as a candidate biomarker of neuropathic pain. We aimed to investigate the levels of LPA, LPC, and ATX in patients with lumbar spinal canal stenosis (LSCS) or other neuropathic pain diseases, and to distinguish the underlying mechanism of LSCS from other neuropathic pain conditions. Furthermore, the levels of phosphorylated neurofilament heavy chain (pNF-H), an objective surrogate marker of axonal damage, were also measured. Cerebrospinal fluid (CSF) samples were obtained from 56 patients with LSCS (n = 31) and various etiologies other than LSCS (n = 25). Patients with LSCS complained of pain intensity comparable to that of patients without LSCS. The LPA levels were significantly higher in patients with LSCS than in non-LSCS patients, while the ATX levels were significantly lower. However, the differences in LPC and pNF-H levels between the two patient groups were not significant. The LPA/LPC ratio was significantly higher in the LSCS group. Notably, the difference in LPA between the two groups diminished in the analysis of covariance (ANCOVA) with ATX as a covariate. Thus, it helped to reveal that LPA synthesis in patients with LSCS depends more efficiently on ATX than in non-LSCS neuropathic pain patients with other etiologies. Our findings further suggest that the triad of LPA, LPC, and ATX in LSCS may contribute to the development and maintenance of neuropathic pain in a manner different from non-LSCS neuropathic conditions.

393 Young Scholar Award Talk: Investigation of Pain and Analgesic Strategies in Cattle Undergoing Painful Husbandry Procedures and Disease Conditions

Abstract Cattle are stoic by nature and have long been subject to evolutionary pressure to mask pain to avoid becoming prey. Quantifying pain via biomarkers allows researchers to capture changes that are not easily detected by the human eye. Negative public perception of routine husbandry practices such as dehorning and castration is growing, increasing the need for the development of practices to relieve pain and suffering in cattle. The objective was to quantify pain associated with induced bacterial pneumonia, scoop and hot-iron dehorning, surgical castration, and hot-iron branding, and to investigate analgesic effectiveness. Calves were experimentally inoculated with Mannheimia haemolytica, scoop or cautery dehorned, surgically castrated, or hot-iron branded. Outcome variables were collected at baseline and following husbandry procedures and included serum cortisol; infrared thermography (IRT); mechanical nociceptive threshold (MNT); substance P; kinematic gait analysis; a visual analog scale; chute defense and behavior scoring; clinical illness score; computerized lung score; average activity and rumination; prostaglandin E2 metabolite; plasma serum amyloid A and rectal temperature. Responses were analyzed using repeated measures with calf nested in treatment designated as a random effect, and treatment, time, and their interaction designated as fixed effects. A combination of reduced activity levels, decreased force on calves’ right front limb, and increased visual analog scale pain scores all support that bacterial pneumonia in cattle is painful (P ≤ 0.01). Differences in right front force were observed in calves challenged with M. haemolytica and treated with flunixin transdermal (96.5 kg) and those given a placebo (85.5 kg), indicating that flunixin transdermal may attenuate specific pain biomarkers in cattle with respiratory disease (P < 0.01). Administration of a bupivacaine liposome suspension block at the time of dehorning and castration was as effective at controlling pain as a multi-modal approach of lidocaine and meloxicam (as evidenced by treatment differences in MNT, cortisol and gait analysis (P ≤ 0.04)). Oral meloxicam administration at branding reduced IRT differences from the branding and control site and reduced lying bouts (P < 0.01). Breed and sex effects were observed across a wide range of biomarkers and should be investigated in future pain studies. The need for long-acting analgesic options for cattle that demonstrate pain alleviation across multiple biomarkers is apparent and would be beneficial to alleviating pain from routine husbandry procedures like dehorning, castration, and branding, as well as painful disease conditions such as bovine respiratory disease.

Evaluation of Chronic Constriction Injury Induced Neuropathic Pain using Chrysin in Rats

Abstract: Introduction: The exhaustive literature review suggested the vast pharmacological profile of chrysin but this drug has not been scientifically reported in the healing of nerve pain till date. The nerve pain is linked with various diseases such as cancer, inflammation, diabetic and mental problems. Neuropathic pain has been viably prompted in rodents by chronic constriction injury (CCI) of sciatic nerve. Objectives: The natural phytoconstituent chrysin will be investigated for neuropathic pain using well established models. Methods:The neuroprotective action of chrysin on neuropathic pain and tissue biomarkers was measured using standardized experimental tests reported in references books. Results:The delivery of chrysin (50 and 100 mg/kg; p.o.) for 15 continuous days showed critical neuropathic pain inhibitory action with respect to control and measurably identical to standard medication in all experimental models via dose dependent manner. The level of TBARS was declined by chrysin for the 15 days while levels of reduced glutathione and total protein were expanded with respect to control and measurably identical to standard medication. Chrysin is one of huge herbal medication to rummage free radicals in the natural structure and it also control the free radical related lipid peroxidation process in the pathogenesis of neuropathic pain. Conclusion: It can be concluded that, extraordinary expansive assessments are required to develop this medicinal activity by using distinctive animal model of neuropathic pain. Additionally, growing the healing impact of chrysin and various flavonoids may give exceptional assistance to finish the further examination in clinical research plan. Key words: Biomarker, Chrysin, Flavonoid, Gabapentin, Neuropathy, Pain.

White matter hyperintensities in Burning Mouth Syndrome assessed according to the Age-Related White Matter Changes scale

BackgroundWhite matter hyperintensities (WMHs) of the brain are observed in normal aging, in various subtypes of dementia and in chronic pain, playing a crucial role in pain processing. The aim of the study has been to assess the WMHs in Burning Mouth Syndrome (BMS) patients by means of the Age-Related White Matter Changes scale (ARWMCs) and to analyze their predictors.MethodsOne hundred BMS patients were prospectively recruited and underwent magnetic resonance imaging (MRI) of the brain. Their ARWMCs scores were compared with those of an equal number of healthy subjects matched for age and sex. Intensity and quality of pain, psychological profile, and blood biomarkers of BMS patients were further investigated to find potential predictors of WMHs. Specifically, the Numeric Rating Scale (NRS), Short-Form McGill Pain Questionnaire (SF-MPQ), Hamilton rating scale for Depression and Anxiety (HAM-D and HAM-A), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) were administered.ResultsThe BMS patients presented statistically significant higher scores on the ARWMCs compared to the controls, especially in the right frontal, left frontal, right parietal-occipital, left parietal-occipital, right temporal and left temporal lobes (p-values: <0.001, <0.001, 0.005, 0.002, 0.009, 0.002, and <0.001, respectively). Age, a lower educational level, unemployment, essential hypertension, and hypercholesterolemia were correlated to a higher total score on the ARWMCs (p-values: <0.001, 0.016, 0.014, 0.001, and 0.039, respectively). No correlation was found with the blood biomarkers, NRS, SF-MPQ, HAM-A, HAM-D, PSQI, and ESS.ConclusionPatients with BMS showed a higher frequency of WMHs of the brain as suggested by the higher ARWCs scores compared with the normal aging of the healthy subjects. These findings could have a role in the pathophysiology of the disease and potentially affect and enhance pain perception.

Kynurenic acid as chronic pain biomarker for future cancer pain management

The prevalence of chronic pain ranges from 30-50% in patients with cancer undergoing active therapy. Kynurenic acid, xanthurenic acid, and quinolinic acid are significant biomarkers for assessing pain objectively. This study aims to investigate the scientific evidence of the effect of serum kynurenic acid levels on the severity and duration of chronic cancer pain. It is a cross-sectional study with 80 subjects consisting of 19 male and 61 female patients in the palliative outpatient clinic of Dr Soetomo Hospital. The pain assessment was performed using the NRS, and the biochemical analysis of serum kynurenic acid was assessed using the ELISA method. Of the total of 80 subjects, 26 patients had pelvic organ cancer (33.7%), 24 patients had respiratory organ cancer (30.1%), 17 patients had breast cancer (21.7%), 9 patients had abdominal organ cancer (9.6%), 3 patients had malignant melanoma (3.6%), and 1 patient had sternal bone cancer (1.2%). Kynurenic acid significantly correlated with the severity of pain (p = 0.043), with (r) of -0.218. However, kynurenic acid showed no significant correlation with the duration of pain (p = 0.052). Kynurenic acid affected the severity of pain but did not affect the duration of pain in chronic cancer pain patients.

A Randomized Controlled Trial Evaluating the Levels of the Biomarkers hs-CRP, IL-6, and IL-8 in Patients with Temporomandibular Disorder Treated with LLLT, Traditional Conservative Treatment, and a Combination of Both.

Temporomandibular disorders (TMDs) are a type of idiopathic orofacial pain. Inflammation, particularly elevated circulating levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and interleukin-8 (IL-8), has been linked to pain symptoms. The purpose of this study was to compare hs-CRP, IL-6, and IL-8 biomarkers and pain intensity with different treatment strategies (LLLT, standard conservative treatment, and combination) for TMD patients. Methods: A total of 32 participants were randomly included in the study and divided into three groups (Group I, Group II, and Group III) referred from the Dental Clinic, School of Dental Science, HUSM. Patients received LLLT (Groups II and III) in five sessions for the duration of 10 days. Patients in Groups I and III received standard conservative TMD treatment (diet and stress counseling, jaw exercises, physical therapy, which was a hot towel application) by the principal investigator. All blood samples for biomarkers were performed before starting treatments and directly after finishing the treatment protocols, where all results were recorded. Results: The result showed a significant difference in the mean IL-8 (p = 0.001) between the three intervention groups (LLLT, standard treatment, and combined treatment). IL-6 showed an increase in the mean of IL-6 levels from baseline to post-treatment with a better mean in the LLLT treatment group without any significant differences. Additionally, there were no significant mean differences found between the groups and in the group for the hs-CRP biomarker. Conclusions: A statistically non-significant difference was found in hs-CRP and IL-6 before and after LLLT, conservative, and combined treatment strategies of TMD. A statistically significant difference was observed in the mean levels of IL-8 between the LLLT intervention group and the combined treatment group. Although there was no statistically significant correlation between pain intensity and biomarkers, a statistically significant difference was found in pain intensity before and after LLLT, conservative, and combined treatment strategies. TMJ degeneration could be exacerbated by elevated IL-8 levels. Thus, this can be an important biomarker to mark or identify the painful condition of TMJ.

Changes in serum angiogenic factors among patients with acute pain and subacute pain.

Screening serum biomarkers for acute and subacute pain is important for precise pain management. This study aimed to examine serum levels of angiogenic factors in patients with acute and subacute pain as potential biomarkers. Serum samples were collected from 12 healthy controls, 20 patients with postherpetic neuralgia (PHN), 4 with low back pain (LBP), and 1 with trigeminal neuralgia (TN). Pain intensity in these patients was evaluated using the visual analog scale (VAS). The serum concentrations of 11 angiogenic biomarkers were examined by Milliplex Map Human Angiogenesis Magnetic Bead Panel 2. The pain assessment from VAS showed that all patients showed moderate and severe pain. Among 11 angiogenic factors, osteopontin (OPN), thrombospondin-2 (TSP-2), soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1), soluble urokinase-type plasminogen activator receptor (suPAR), and soluble epidermal growth factor receptors (sErbB2) were up-regulated and soluble interleukin-6 receptor α (sIL-6Rα) were down-regulated in patients with pain compared to the healthy participants (all P-values were < 0.005). Moreover, a linear regression model showed that the serum OPN concentration was correlated with pain intensity in patients with PHN (P = 0.03). There was no significant difference between the serum concentration of soluble epidermal growth factor receptors, sErbB3, soluble AXL, tenascin, and soluble neuropilin-1 in patients with acute and subacute pain and that of healthy controls. The results of this study provided new valuable insights into our understanding of angiogenic factors that may contribute to as mechanistic biomarkers of pain, and reveal the pathophysiological mechanism of pain.Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR2200061775.

Paper 33: Serum and Urine Biomarkers for Treatment Monitoring after Meniscal Allograft Transplantation in a Preclinical Canine Model

Objectives:To analyze serum and urine biomarker concentrations for their capabilities in delineating differences in assessments of pain and functional outcomes after meniscus allograft transplantation (MAT) in a preclinical canine model. The study was designed to test the hypothesis that serum and urine biomarkers could be used for prognostic (1- and 3-month post-surgical time points) and diagnostic (6-month time point) assessments, based on strong associations with clinically relevant pain and function outcomes after MAT.Methods:Twelve adult, purpose-bred research hounds were included and underwent medial meniscal release (MR) to induce medial compartment gonarthrosis. Three months following MR, medial MAT was performed using: fresh-frozen meniscus (n=4), fresh meniscus (n=4), or fresh menisco-tibial OCA (n=4). Serum and urine from all dogs were collected preoperatively and at 1, 3, and 6 months following MAT. Validated outcome measures for pain, function, effusion, knee range of motion, and gait kinetics were collected at these same timepoints. To develop a prognostic panel of biomarkers, biomarker data from the 1-month and 3-month post-MAT surgery timepoints were used to model 6-month outcomes. A diagnostic panel of biomarkers was developed using biomarker data from the 6-month post-MAT surgery to model 6-month outcomes.Results:Across prognostic biomarker panels, serum biomarkers were mainly represented. A panel including serum IL-6, IL-8, IL-10, and IL-18 had strong model fit for prognostication of the gait kinetics outcome, operated limb %Total Pressure Index (%TPI) (R2=.45). Whereas, a biomarker panel including serum CTX-II and OPG had strong model fit for prognostication of the primary pain-related outcome, VAS pain (R2=.52). Across diagnostic biomarker panels, a panel including serum MMP-1 and MMP-3 and urine PINP and TIMP-1 had strong model fit as diagnostic biomarkers for %TPI (R2=.86). Whereas, a panel including urine CTX-I, CTX-II, IL-8, MMP-2, and TIMP-1 had strong model fit as diagnostic biomarkers for VAS pain (R2=.44).Conclusions:Biomarker panels of selected serum and/or urine proteins highly correlate with clinically-relevant metrics for pain and function outcomes in a preclinical model of meniscus allograft transplantation.

ID:16245 REALITY Sub-Study: Developing an Objective Pain Score for Patients With Implanted Spinal Cord Stimulation

Spinal cord stimulation (SCS) is a well-established therapy for the treatment of chronic, intractable pain which reduces pain and improves quality of life [1]. Despite considerable efforts toward establishing biomarkers of pain, methods to objectively measure pain are esoteric. The goal of this study is to develop objective measures of physiologic and behavioral markers during SCS treatment using commercially available smartwatches and corroborate these assessments to the patient-reported outcomes (PRO).

Transient receptor potential (TRP) channels mRNA transcripts in the lumbar intervertebral discs: biomarkers for inflammation, pain, disability, and clinical outcome.

Transient receptor potential (TRP) channels are widely expressed cation channels that play an essential role in mediating Ca2+ homeostasis and are considered potential regulators of inflammatory pain. This study investigates the expression of the TRP channel subtypes TRPV1, TRPV4, TRPC6, TRPM2, TRPM8 in lumbar intervertebral disc (IVD) biopsies from patients with chronic low back pain (LBP). We determined the expression of these TRP channel subtypes in the annulus fibrosus (AF) and the nucleus pulposus (NP) from 46 patients with LBP undergoing 1-2 level lumbar fusion surgery for degenerative disc disease. The mRNA transcripts were analyzed using quantitative real-time polymerase chain reaction (RT-qPCR), and the expression levels were compared against visual analog scale (VAS) and oswestry disability index (ODI) scores (0-100) for pain and disability. A significant positive correlation was demonstrated between VAS score and the mRNA expression of TRPV1, TRPC6, TRPM2, TRPM8 in the AF. We also found a significant positive correlation between ODI scores and expression of TRPV1 and TRPM8. Further, there is a significant positive correlation between TNF-α and TRPV1, TRPM2 and TRPM8 expression in the AF, and IL-6 to TRPV1 in the NP. Interestingly, when investigating treatment response via a 12-month postoperative follow-up ODI, we found a significant correlation between only TRPV1 expression at baseline and the follow-up ODI scores, which indicates this marker could predict the effectiveness of surgery. These results strongly suggest an association between pain, inflammatory mediators, and TRP channel expression in lumbar disc biopsies of patients with chronic LBP.

Substance P concentrations in the blood plasma and serum of adult cattle and calves during different painful procedures and conditions – a systematic review

BackgroundPain in cattle is a major welfare problem, as cattle mask their pain. Subjective and objective parameters to assess pain in cattle have been described. Among the objective parameters to evaluate pain in cattle is substance P (SP). SP is a neurotransmitter, which is involved in the processing of noxious information to the brain; it seems to be a more objective indicator for nociception than cortisol, which has long been used as a biomarker for pain and stress in cattle. The objective of this systematic review was to assess the existing literature about SP during painful procedures, conditions, and diseases in cattle in form of a systematic review.ResultsFollowing the PRISMA statement, 36 out of 236 studies were included in this systematic review. Study design, grouping, age and weight of animals, processing of blood samples for the assessment of SP, and results were heterogenous. The largest number of studies originated from the United States of America and Canada and were published in 2018. A higher number of studies were done on calves (69.4%, n = 25) compared with adult cattle (30.6%, n = 11). Most studies were done to assess SP concentrations after administration of analgesics prior to husbandry procedures in calves.ConclusionsThere is a manageable number of studies assessing SP concentrations during painful procedures, conditions, and diseases in cattle. SP seems to be a suitable biomarker for nociception in cattle, but results of research work are heterogenous, and SP concentrations of calves and adult cattle differ throughout studies. Basic research work is missing and is needed to assess factors others than nociception which might influence the SP concentrations in the blood plasma.

IL-1Ra and sVCAM-1 in chikungunya virus infection

Mediators involving in inflammation induction and regulation have been investigated as biomarkers for severe joint pain induced by chikungunya virus (CHIKV) infection. In this report, observational study was conducted to determine levels of an antagonist of interleukin-1 receptor (IL-1Ra) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in CHIKV patients with different disease severity. CHIKV infection patients presented without (n = 199) and with joint pain (n = 262) were included. IL-1Ra and sVCAM-1 levels in patient sera were determined. Levels of sVCAM-1 were strongly and significantly higher in the group of patients with joint pain than in the group without joint pain (p < 0.0001). The levels of both IL-1Ra and sVCAM-1 were not significantly increased with age.

Meditation and yoga impact on dysmenorrhea (MY-ID): a study protocol

Primary dysmenorrhea is one of the most prevalent gynecologic condition affecting women, especially adolescent girls. Among adolescents, associated symptoms of dysmenorrhea impact the general health status, negatively influence the quality of life, resulting in school absenteeism and decreased academic performance. This study protocol was developed to estimate the prevalence of dysmenorrhea and evaluate the effectiveness of Meditation and Yoga intervention on dysmenorrhea among adolescent girls. In phase I, data will be collected from adolescent girls (N» 5000) aged between 13 and 18 years to estimate the prevalence of dysmenorrhea and in the second phase, Cluster-Randomized Controlled Trial will be conducted to evaluate the impact of Meditation and Yoga on dysmenorrhea. From the first phase, those adolescent girls (N=400) with high pain intensity (numerical pain rating scale ≥ 4) from each school, with schools as clusters, will be assigned to the interventional and control arm. The interventional arm will receive the proposed Meditation and Yoga intervention for 12 weeks under supervision and the control arm will continue with standard routine care. The outcomes such as pain intensity, stress, academic performance, self-efficacy and biomarker levels (Hb, Progesterone, Estrogen, Prostaglandins F2α and E2) will be assessed at baseline and 12 weeks after the intervention. Yoga's popularity and medical benefits have grown with the growing interest in alternative and complementary medicine. There is insufficient evidence to support yoga as a treatment for dysmenorrhea symptoms. This research contributes to the evidence on the impact of meditation and yoga on primary dysmenorrhea among adolescent girls.

Apoptosis and (in) Pain-Potential Clinical Implications.

The deregulation of apoptosis is involved in the development of several pathologies, and recent evidence suggests that apoptosis may be involved in chronic pain, namely in neuropathic pain. Neuropathic pain is a chronic pain state caused by primary damage or dysfunction of the nervous system; however, the details of the molecular mechanisms have not yet been fully elucidated. Recently, it was found that nerve endings contain transient receptor potential (TRP) channels that sense and detect signals released by injured tissues and respond to these damage signals. TRP channels are similar to the voltage-gated potassium channels or nucleotide-gated channels that participate in calcium and magnesium homeostasis. TRP channels allowing calcium to penetrate into nerve terminals can activate apoptosis, leading to nerve terminal destruction. Further, some TRPs are activated by acid and reactive oxygen species (ROS). ROS are mainly produced in the mitochondrial respiratory chain, and an increase in ROS production and/or a decrease in the antioxidant network may induce oxidative stress (OS). Depending on the OS levels, they can promote cellular proliferation and/or cell degeneration or death. Previous studies have indicated that proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), play an important role in the peripheral mediation of neuropathic pain. This article aims to perform a review of the involvement of apoptosis in pain, particularly the role of OS and neuroinflammation, and the clinical relevance of this knowledge. The potential discovery of new biomarkers and therapeutic targets can result in the development of more effective and targeted drugs to treat chronic pain, namely neuropathic pain. Highlights: Oxidative stress and neuroinflammation can activate cell signaling pathways that can lead to nerve terminal destruction by apoptosis. These could constitute potential new pain biomarkers and targets for therapy in neuropathic pain.

Efficacy of the use of chondroitin sulphate and glucosamine for the treatment of temporomandibular joint dysfunction: A systematic review and meta-analysis

ABSTRACT Objective To evaluate the efficacy of chondroitin sulfate (CS) and glucosamine (GS), the most relevant drugs of “Symptomatic Slow Acting Drug for Osteoarthritis” (SYSADOA), in the functional and symptomatic improvement of temporomandibular dysfunction. Although, controversy exists regarding their benefit. Methods An electronic search was conducted to retrieve randomized controlled clinical trials (RCTs). The risk of bias assessment was evaluated using the Cochrane Collaboration’s tool. Data were meta-analyzed with a random effect model whenever possible. Results Three RCTs were included. Qualitative results showed a decrease in pain, joint noise, and inflammatory biomarkers in synovial fluid and an improvement in maximum mouth opening without significant adverse effects. Meta-analysis showed a significant increase in maximum mouth opening with the use of CS-GS (p = 0.19). No statistically significant differences were found in pain reduction compared to tramadol. Conclusion CS-GS is effective and safe in the symptomatic and functional improvement of patients with TMD.