Sensory Pain Perception Research Articles

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

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

Early detection of diabetic peripheral neuropathy using EMLA-induced skin wrinkling

Background & Objective: Screening for early diabetic peripheral neuropathy (DN) is essential for foot ulcer prevention. The Semmes–Weinstein monofilament (SWMF) is commonly used to detect DN in Thailand. However, SWMF interpretation requires patient participation, which is susceptible to risk of error in patients with impaired cognitive function or uncooperative patients. In contrast, stimulated skin wrinkling (SSW) can be interpreted by trained investigators, which is more appropriate. This study aimed to investigate the utility of SSW using a eutectic mixture of local anesthetic (SSW-EMLA) for early DN diagnosis. Methods: This cross-sectional study, recruited 102 patients with diabetes (DM group), 33 with diabetes with foot ulcer (DN control group), and 30 without diabetes (non-DN control group) from the Faculty of Medicine, Vajira Hospital, Navamindradhiraj University, Thailand, from February 3, 2021 to November 30, 2021. SSW was conducted by applying EMLA on the tips of the 2nd, 3rd, and 4th fingers of both hands. SWMF, sensory perception of pain (SPP), vibration perception threshold (VPT), joint position sense (JPS), and deep tendon reflexes (DTR) were also evaluated on the same day. Results: The Interrater agreement of two investigators for SSW-EMLA was high with intraclass correlation coefficients of 0.87 (0.824–0.904) for the right hand and 0.874 (0.830–0.907) for the left hand. The kappa coefficients of agreement of SSW-EMLA for SPP, SWMF, VPT, JPS, and DTR testing were 0.411, 0.478, 0.714, 0.444, and 0.681, respectively. The sensitivity and specificity of SSW-EMLA testing for DN detection were 83.3%, was 85.7%, respectively. Conclusion: The SSW-EMLA test can be considered as an alternative method for DN detection, due to its noninvasiveness, inexpensiveness (50THB), being a simple procedure, high sensitivity and specificity, and acceptable rater variation.

Multi-animal-model study reveals mutations in neural plasticity and nociception genes linked to excessive alcohol drinking.

The basis for familial alcohol use disorder (AUD) remains an enigma due to various biological and societal confounds. The present study used three of the most adopted and documented rat models, combining the alcohol-preferring/non-alcohol-preferring (P/NP) lines and high alcohol-drinking/low alcohol-drinking (HAD/LAD) replicated lines, of AUD as examined through the lens of whole genomic analyses. We used complete genome sequencing of the P/NP lines and previously published sequences of the HAD/LAD replicates to enhance the discovery of variants associated with AUD and to remove confounding with genetic background and random genetic drift. Specifically, we used high-order statistical methods to search for genetic variants whose frequency changes in whole sets of gene ontologies corresponded with phenotypic changes in the direction of selection, that is, ethanol-drinking preference. Our first finding was that in addition to variants causing translational changes, the principal genetic changes associated with drinking predisposition were silent mutations and mutations in the 3' untranslated regions (3'UTR) of genes. Neither of these types of mutations alters the amino acid sequence of the translated protein but they influence both the rate and conformation of gene transcription, including its stability and posttranslational events that alter gene efficacy. This finding argues for refocusing human genomic studies on changes in gene efficacy. Among the key ontologies identified were the central genes associated with the Na+ voltage-gated channels of neurons and glia (including the Scn1a, Scn2a, Scn2b, Scn3a, Scn7a, and Scn9a subtypes) and excitatory glutamatergic secretion (including Grm2 and Myo6), both of which are essential in neuroplasticity. In addition, we identified "Nociception or Sensory Perception of Pain," which contained variants in nociception (Arrb1, Ccl3, Ephb1) and enlist sodium (Scn1a, Scn2a, Scn2b, Scn3a, Scn7a), pain activation (Scn9a), and potassium channel (Kcna1) genes. The multi-model analyses used herein reduced the confounding effects of random drift and the "founders" genetic background. The most differentiated bidirectionally selected genes across all three animal models were Scn9a, Scn1a, and Kcna, all of which are annotated in the nociception ontology. The complexity of neuroplasticity and nociception adds strength to the hypothesis that neuroplasticity and pain (physical or psychological) are prominent phenotypes genetically linked to the development of AUD.

A longitudinal mediation study of peer victimization and resting-state functional connectivity as predictors of development of adolescent psychopathology.

Peer victimization (PV) is associated with alterations in neural responses in regions subserving emotional regulatory processes and with increased risk of psychopathology during adolescence. The present study examined the longitudinal mediating effects of resting-state functional connectivity (rsFC) between adolescent PV and subsequent internalizing (depression and anxiety), and externalizing (conduct and hyperactivity/inattention) symptoms. 151 adolescents (baseline mean age 12-14; 54% males) were assessed and imaged three times during a five-year period. We focused on rsFC of a priori determined Regions-of-Interest (ROIs) guided by the literature (i.e., amygdala, anterior and posterior insula, anterior cingulate cortex, and medial prefrontal cortex). Multilevel mediation (MLM) analyses simultaneously examined the between-person, concurrent within-person, and lagged within-person associations between PV and internalizing/externalizing symptoms through changes in couplings of the amygdala with the other four ROIs. All models controlled for the effects of self-reported childhood maltreatment and sex differences. An increased rsFC of the amygdala-posterior insula significantly mediated the lagged within-person association of PV and internalizing symptoms (β = 0.144; 95% CI [0.018, 0.332]). This effect was significant regardless of childhood maltreatment, concurrent externalizing symptoms, and sex differences. The rsFC did not mediate the relationship between PV and externalizing symptoms. Results of this study suggest that adolescent PV may lead to long-lasting maladaptive neural communication between emotional response and sensory perception of pain (i.e., bottom-up emotion regulation) and that these neural responses may serve as unique markers for increased internalizing symptoms that appear in later adolescence in peer-victimized youth. These findings have implications for interventions targeting internalizing symptoms in victimized adolescents.

Meis1 Regulates Nociceptor Development and Behavioral Response to Tactile Stimuli.

Nociceptors in the dorsal root ganglia (DRG) and trigeminal ganglia (TG) are necessary for transmitting pain and itch signals. However, the molecular mechanism regulating nociceptor development remains largely unknown. This study identifies that the transcription factor Meis1 is generally expressed in two groups of sensory neurons in the developing DRG. During prenatal and neonatal stages, approximately 2/3 of Meis1+ neurons are Runx1+ nociceptors, while 1/3 of Meis1+ neurons are NF200+ myelinated neurons. At postnatal stages, Meis1 expression in nociceptors is gradually reduced. Here, we constructed a Meis1 conditional knockout mouse line to selectively delete Meis1 in Nav1.8 lineage nociceptors. Microarray analyses showed that differentially expressed genes in the Meis1 mutant DRG were enriched in pathways related to sensory perception of pain and nervous system development. In addition, Meis1 regulates the expression of some marker genes of Nppb+ neurons and C-LTMRs. Furthermore, Meis1 mutant mice exhibit behavioral deficits in response to light mechanical pain, static touch and chemical itch. Therefore, this study reveals that Meis1 is required to regulate the development of nociceptors.

Molecular Structure, Expression and Role of TAFA4 and its Receptor FPR1 in the Spinal Cord

TAFA chemokine like family member 4 (TAFA4, also named FAM19A4) is a member of the TAFA chemokine like ligand or FAM19A family, which includes TAFA1, TAFA2, TAFA3, TAFA4, and TAFA5 (or FAM19A1, FAM19A2, FAM19A3, FAM19A4, and FAM19A5). They are also referred to as neurokines and are involved in the regulation of a diverse range of cellular processes, including chemotaxis of macrophages, phagocytosis, and release of reactive oxygen species (ROS). TAFA4 is a marker of C-low-threshold mechanoreceptors and is expressed predominantly in nociceptors, such as dorsal root ganglia (DRG). TAFA4 has been implicated in the sensory perception of pain in the spinal cord. Mice with deficiency of TAFA4 demonstrate altered excitability in lamina IIi neurons in DRG in addition to increased mechanical and chemical nociception following inflammation or injury. As a secreted protein, TAFA4 binds to cell surface receptor formyl peptide receptor 1 (FPR1), a G protein-coupled receptor to mediate the chemoattraction of macrophages, phagocytosis, and the inflammatory profile of macrophages. It also interacts with cell surface neurexin to mediate signalling across the synapse. Further understanding the mechanisms by which this conserved protein family regulates diverse biological processes such as in neuronal functions, inflammation, and tissue fibrosis will help to design therapeutic targets for the treatment of TAFA related diseases such as spinal cord injury and neuro-inflammatory disorders.

Transcriptomic analysis supports collective endometrial cell migration in the pathogenesis of adenomyosis

Research questionAdenomyosis is a common uterine disorder of uncertain causes. Can transcriptomic analyses of the endometrium and myometrium reveal potential mechanisms underlying adenomyosis pathogenesis? DesignTranscriptomic profiles of eutopic endometrium and myometrium from women with and without diffuse adenomyosis and with symptomatic FIGO type 2–5 fibroids in the proliferative phase of the menstrual cycle were assessed using RNA sequencing and bioinformatic analysis. Differentially expressed genes (DEG) and potential pathways were validated by quantitative reverse transcription polymerase chain reaction, immunoblotting and Masson staining, using additional clinical samples. ResultsTop biological processes in the endometrium of women with versus without adenomyosis, enriched from DEG, comprised inflammation, extracellular matrix (ECM) organization, collagen degradation and hyaluronan synthesis, which are key in cell migration and cell movement. Top biological processes enriched from DEG in the myometrium of women with versus without adenomyosis revealed ECM organization dysfunction, abnormal sensory pain perception and gamma aminobutyric acid (GABA) synaptic transmission. Dysregulation of prolactin signalling was also enriched in eutopic endometrium and in the myometrium of women with adenomyosis. ConclusionsOverall, our results support the invasive endometrium theory in the pathogenesis of adenomyosis, in which inflammation induces ECM remodelling resulting in a track for subsequent endometrial collective cell migration and onset of adenomyosis. Moreover, abnormal myometrial GABA synaptic transmission may contribute to dysmenorrhoea in women with adenomyosis and is a possible target for novel therapeutic development. Prolactin signalling abnormalities may serve as another opportunity for therapeutic intervention.

No Gender Differences in Pain Perception and Medication after Lumbar Spine Sequestrectomy—A Reanalysis of a Randomized Controlled Clinical Trial

Background: Gender issues have received increasing attention in clinical research of the past years, and biological sex has been introduced as a moderating variable in experimental pain perception. However, in clinical studies of acute pain and gender, there are conflicting results. In particular, there are limited data on the impact of gender differences after spinal sequestrectomy. The aim of this work is to examine gender differences in postoperative pain and pain medication consumption in an inpatient clinical setting. Methods: Data of a completed double-blind RCT was subdivided by gender and reanalyzed by means of an analysis of variance in repeated measures. Outcomes included pain severity measured on a VAS, affective (SES-A) and sensory pain perception (SES-S) and morphine equivalent doses (MED) of analgesics after spinal sequestrectomy. Results: In total, 42 female (47.73%) and 46 male (52.27%) patients were analyzed. No differences in pain severity (VAS: Gender × Time F = 0.35; (df = 2, 86); p = 0.708), affective and sensory pain perception (SES-A: Gender × Time F = 0.08; (df = 2, 86); p = 0.919; SES-S: Gender × Time F = 0.06; (df = 2, 86); p = 0.939) or post-operative opioid use between men and women (MEDs: Gender × Time F = 1.44; (df = 2, 86); p = 0.227) could be observed. Conclusions: This reanalysis of an RCT with respect to gender differences is to our knowledge the first attempt to investigate the role of gender in pain perception and medication after lumbar spine sequestrectomy. In contrast to other studies, we were not able to show significant differences between male and female patients in all pain-related outcomes. Apart from well-established pain management, psychological reasons such as gender-specific response biases or the observer effect might explain our results. Trial registration: The study was registered as a regulatory phase IV study at the German Clinical Trials Register (DRKS), an open-access online register for clinical trials conducted in Germany (Reg-No: DRKS00007913).

Genome-Wide Expression Profiling by RNA-Sequencing in Spinal Cord Dorsal Horn of a Rat Chronic Postsurgical Pain Model to Explore Potential Mechanisms Involved in Chronic Pain.

BackgroundChronic postsurgical pain (CPSP) is common among patients receiving major surgeries. CPSP produces suffering in patients, both physically and mentally. However, the mechanisms underlying CPSP remain elusive. Here, a genome-wide expression profiling of ipsilateral spinal cord dorsal horn (SCDH) was performed to identify potential genes related with CPSP.MethodsA rat skin/muscle incision and retraction (SMIR) model was established to induce CPSP. Immunostaining was used to study glial cell and neuron activation in ipsilateral SCDH of SMIR model rats. RNA sequencing (RNA-Seq), combined with bioinformatics analysis, was undertaken to explore gene expression profiles. qPCR was applied to validate the expression of some representative genes.ResultsThe SMIR model rats developed persistent mechanical allodynia in ipsilateral hindpaw for up to 14 days. Ipsilateral SCDH of SMIR rats showed remarkable glial cell and neuron activation. A number of differentially expressed genes (DEGs) were identified in ipsilateral SCDH of SMIR rats by RNA-Seq. qPCR confirmed expression of some representative DEGs. Bioinformatics indicated that chemical synaptic transmission, sensory perception of pain and neuroactive ligand-receptor interaction were predominant functions. We compared our dataset with human pain-related genes and found that several genes exclusively participate in pain modulation and mechanisms.ConclusionOur study provided novel understandings of the molecular mechanisms possibly contributing to CPSP. These findings may offer new targets for future treatment of CPSP.

Gene Transcript Alterations in the Spinal Cord, Anterior Cingulate Cortex, and Amygdala in Mice Following Peripheral Nerve Injury.

Chronic neuropathic pain caused by nerve damage is a most common clinical symptom, often accompanied by anxiety- and depression-like symptoms. Current treatments are very limited at least in part due to incompletely understanding mechanisms underlying this disorder. Changes in gene expression in the dorsal root ganglion (DRG) have been acknowledged to implicate in neuropathic pain genesis, but how peripheral nerve injury alters the gene expression in other pain-associated regions remains elusive. The present study carried out strand-specific next-generation RNA sequencing with a higher sequencing depth and observed the changes in whole transcriptomes in the spinal cord (SC), anterior cingulate cortex (ACC), and amygdala (AMY) following unilateral fourth lumbar spinal nerve ligation (SNL). In addition to providing novel transcriptome profiles of long non-coding RNAs (lncRNAs) and mRNAs, we identified pain- and emotion-related differentially expressed genes (DEGs) and revealed that numbers of these DEGs displayed a high correlation to neuroinflammation and apoptosis. Consistently, functional analyses showed that the most significant enriched biological processes of the upregulated mRNAs were involved in the immune system process, apoptotic process, defense response, inflammation response, and sensory perception of pain across three regions. Moreover, the comparisons of pain-, anxiety-, and depression-related DEGs among three regions present a particular molecular map among the spinal cord and supraspinal structures and indicate the region-dependent and region-independent alterations of gene expression after nerve injury. Our study provides a resource for gene transcript expression patterns in three distinct pain-related regions after peripheral nerve injury. Our findings suggest that neuroinflammation and apoptosis are important pathogenic mechanisms underlying neuropathic pain and that some DEGs might be promising therapeutic targets.

DIFFERENT MUSCULOSKELETAL PAINS AND SOCIOCULTURAL FEATURES: THE CASE OF PRIVATE NOBEL PHYSICAL THERAPY AND REHABILITATION MEDICAL CENTER

Aim: It was conducted to evaluate the effect of some sociodemographic and cultural characteristics on pain perception and pain intensity in different musculoskeletal pains and to determine some characteristics related to pain. Method: By recording the demographic information and sociocultural characteristics of all participants; Scandinavian Musculoskeletal Questionnaire and McGill Pain Scale Short Form were used to assess pain perception and pain intensity. Results: 544 patients, 372 women and 172 men, with subacute and chronic musculoskeletal pain were included in this study. The average age of the participants was 40.74±14.53 years. When the effect of sociocultural factors on pain intensity and pain perception (sensory and perceptual dimensions) is examined; it was determined that as the education level increased, the severity of pain (p = 0.002) and pain perception decreased (p = 0.0001), and the pain intensity of the participants living in the village was higher (p = 0.014). While the severity of pain and pain perception were higher in female individuals, it was determined that they also increased with age. When the relationship between pain intensity and pain perception of the participants is examined; positive high relationship (r = 0.630, p = 0.0001) was found between the intensity of pain and sensory pain perception, and a moderate relationship (r = 0.597, p = 0.0001) was found between perceptual dimension. A high positive correlation was found between sensory and perceptual pain dimensions (r = 0.658, p = 0.0001) Conclusion: Chronic pain experience and pain perception levels are affected by social and cultural characteristics. Sociocultural characteristics of individuals should also be taken into consideration in pain relief. Studies examining the effects of different sociocultural characteristics such as language, religious belief, family structure, pet feeding or interaction with animals on musculoskeletal pain are also needed.

Longitudinal Transcriptomic Profiling in Carrageenan-Induced Rat Hind Paw Peripheral Inflammation and Hyperalgesia Reveals Progressive Recruitment of Innate Immune System Components

Pain is a common but potentially debilitating symptom, often requiring complex management strategies. To understand the molecular dynamics of peripheral inflammation and nociceptive pain, we investigated longitudinal changes in behavior, tissue structure, and transcriptomic profiles in the rat carrageenan-induced peripheral inflammation model. Sequential changes in the number of differentially expressed genes are consistent with temporal recruitment of key leukocyte populations, mainly neutrophils and macrophages with each wave being preceded by upregulation of the cell-specific chemoattractants, Cxcl1 and Cxcl2, and Ccl2 and Ccl7, respectively. We defined 12 temporal gene clusters based on expression pattern. Within the patterns we extracted genes comprising the inflammatory secretome and others related to nociceptive tissue remodeling and to sensory perception of pain. Structural tissue changes, involving upregulation of multiple collagens occurred as soon as 1-hour postinjection, consistent with inflammatory tissue remodeling. Inflammatory expression profiling revealed a broad-spectrum, temporally orchestrated molecular and cellular recruitment process. The results provide numerous potential targets for modulation of pain and inflammation. PerspectiveThis study investigates the highly orchestrated biological response during tissue inflammation with precise assessment of molecular dynamics at the transcriptional level. The results identify transcriptional changes that define an evolving inflammatory state in rats. This study provides foundational data for identifying markers of, and potential treatments for, inflammation and pain in patients.

Tinnitus-related distress and pain perceptions in patients with chronic tinnitus - Do psychological factors constitute a link?

ObjectiveTo investigate the co-occurrence of tinnitus-related distress and pain experiences alongside psychological factors that may underlie their association.MethodPatients with chronic tinnitus (N = 1238) completed a questionnaire battery examining tinnitus-related distress and affective and sensory pain perceptions. A series of simple, parallel- and serial multiple mediator models examined indirect effects of psychological comorbidities as well as -process variables including depressivity, perceived stress and coping attitudes. Moderator and moderated mediation analyses examined differential relational patterns in patients with decompensated vs. compensated tinnitus.ResultsThere were significant associations between tinnitus-related distress and pain perceptions. These were partially mediated by most specified variables. Psychological comorbidities appeared to influence tinnitus-pain associations through their impact on depressivity, perceived stress, and coping attitudes. Some specific differences in affective vs. sensory pain perception pathways emerged. Patients with decompensated tinnitus yielded significantly higher symptom burden across all measured indices. Tinnitus decompensation was associated with heightened associations between [1] tinnitus-related distress and pain perceptions, depressivity and negative coping attitudes; and [2] most psychological comorbidities and sensory, but not affective pain perception. Moderated mediation analyses revealed stronger indirect effects of depressivity and anxiety in mediating affective-, and anxiety in mediating sensory pain perception in patients with decompensated tinnitus.ConclusionPsychological constructs mediate the co-occurrence of tinnitus- and pain-related symptoms across different levels of tinnitus-related distress. Psychological treatment approaches should conceptualize and address individualised interactions of common cognitive-emotional processes in addressing psychosomatic symptom clusters across syndromatic patients with varying distress levels.

Melatonin plus Folic Acid Treatment Ameliorates Reserpine‐Induced Fibromyalgia: Evaluation of Pain, Oxidative Stress and Inflammation

BackgroundFibromyalgia is a chronic condition characterized by increased sensory perception of pain, neuropathic/neurodegenerative modifications, oxidative and nitrosative stress. An appropriate therapy is hard to find, and the currently used treatments are able to target only one of these aspects.MethodsThe aim of this study was to investigate the beneficial effects of a melatonin plus folic acid administration in a rat model of reserpine‐induced fibromyalgia. Sprague–Dawley male rats were injected with 1 mg/kg of reserpine for three consecutive days and later administered with melatonin, folic acid or both for twenty‐one days.ResultsAdministration of reserpine led to a significant decrease in nociceptive threshold as well as significant increase in depressive‐like symptoms. These behavioral changes were accompanied with increased oxidative and nitrosative stress. Lipid peroxidation was significantly increased, as well as nitrotyrosine and PARP expression, while superoxide dismutase, nonprotein thiols and catalase were significantly decreased. Endogenously produced oxidants species are responsible of mast cells infiltration, increased expression pro‐inflammatory mediators and microglia activation.ConclusionMelatonin plus acid folic administration was able to ameliorate the behavioral defects, oxidative and nitrosative stress, mast cells infiltration, inflammatory mediators overexpression and microglia activation induced by reserpine injection with more efficacy than them separate administration.

Melatonin Plus Folic Acid Treatment Ameliorates Reserpine-Induced Fibromyalgia: An Evaluation of Pain, Oxidative Stress, and Inflammation.

Background: Fibromyalgia is a chronic condition characterized by increased sensory perception of pain, neuropathic/neurodegenerative modifications, oxidative, and nitrosative stress. An appropriate therapy is hard to find, and the currently used treatments are able to target only one of these aspects. Methods: The aim of this study is to investigate the beneficial effects of melatonin plus folic acid administration in a rat model of reserpine-induced fibromyalgia. Sprague–Dawley male rats were injected with 1 mg/kg of reserpine for three consecutive days and later administered with melatonin, folic acid, or both for twenty-one days. Results: Administration of reserpine led to a significant decrease in the nociceptive threshold as well as a significant increase in depressive-like symptoms. These behavioral changes were accompanied by increased oxidative and nitrosative stress. Lipid peroxidation was significantly increased, as well as nitrotyrosine and PARP expression, while superoxide dismutase, nonprotein thiols, and catalase were significantly decreased. Endogenously produced oxidants species are responsible for mast cell infiltration, increased expression pro-inflammatory mediators, and microglia activation. Conclusion: Melatonin plus acid folic administration is able to ameliorate the behavioral defects, oxidative and nitrosative stress, mast cell infiltration, inflammatory mediators overexpression, and microglia activation induced by reserpine injection with more efficacy than their separate administration.

Early Changes in Pain Acceptance Predict Pain Outcomes in Interdisciplinary Treatment for Chronic Pain.

Studies have shown that pain acceptance is associated with a better pain outcome. The current study explored whether changes in pain acceptance in the very early treatment phase of an interdisciplinary cognitive-behavioral therapy (CBT)-based treatment program for chronic pain predict pain outcomes. A total of 69 patients with chronic, non-malignant pain (at least 6 months) were treated in a day-clinic for four-weeks. Pain acceptance was measured with the Chronic Pain Acceptance Questionnaire (CPAQ), pain outcomes included pain intensity (Numeric Rating Scale, NRS) as well as affective and sensory pain perception (Pain Perception Scale, SES-A and SES-S). Regression analyses controlling for the pre-treatment values of the pain outcomes, age, and gender were performed. Early changes in pain acceptance predicted pain intensity at post-treatment measured with the NRS (B = −0.04 (SE = 0.02); T = −2.28; p = 0.026), affective pain perception at post-treatment assessed with the SES-A (B = −0.26 (SE = 0.10); T = −2.79; p = 0.007), and sensory pain perception at post-treatment measured with the SES-S (B = −0.19 (SE = 0.08); T = −2.44; p = 0.017). Yet, a binary logistic regression analysis revealed that early changes in pain acceptance did not predict clinically relevant pre-post changes in pain intensity (at least 2 points on the NRS). Early changes in pain acceptance were associated with pain outcomes, however, the impact was beneath the threshold defined as clinically relevant.

Depression According to ICD-10 Clinical Interview vs. Depression According to the Epidemiologic Studies Depression Scale to Predict Pain Therapy Outcomes.

PurposePain and depression have been shown to have a bidirectional interaction. Although several outcome studies have been conducted, it is still unclear if and how depression influences pain outcome. The current study aims to further clarify this relationship by comparing the predicting value of an interview- and a questionnaire-based assessment of depression.Patients and MethodsThis retrospective study analyzed data of N = 496 chronic pain patients who received a multimodal pain management program. Multilevel models were performed with depression as predictor, pain measures as dependent variables, and the respective pain score at baseline as covariate. Depression was measured at baseline with (1) a semi-structured psychiatric interview corresponding to the ICD-10 and (2) the Center for Epidemiologic Studies Depression Scale (CES-D). Pain outcomes were pain intensity assessed with the Numeric Rating Scale (NRS), pain disability measured with the pain disability index (PDI), and affective as well as sensory pain perception assessed with the Pain Perception Scale (PPS-A/PPS-S).ResultsAt post-treatment, pain intensity (NRS) was higher in patients with depression. This result emerged for interview- (ICD-10) and questionnaire- (CES-D) based depression. These results were significant after correction for multiple testing as well. Moreover, affective pain perception (PSS-A) at post-treatment was higher in patients with depression. Again, this result emerged for interview- (ICD-10) and questionnaire- (CES-D) based depression but it was not significant anymore after correction for multiple testing. Furthermore, pain disability (PDI) was higher at post-treatment in patients with depression according to the CES-D than in those without CES-D depression and this difference in the PDI did not emerge for interview-based depression. Yet, this difference on the PDI between the CES-D depression group and the CES-D no depression group was not significant anymore after correction for multiple testing.ConclusionThe hypothesis that how depression is assessed – interview-based corresponding to the ICD-10 or with the CES-D – contributes to the association between depression and pain treatment outcome could not be confirmed. Future research should use more than one interview and questionnaire to assess depression, since our results are limited to the clinical ICD-10 interview and the CES-D.

Is Mindfulness-Based Stress Reduction a Promising and Feasible Intervention for Patients Suffering from Migraine? A Randomized Controlled Pilot Trial

Aim: We performed a pilot study in order to evaluate the feasibility and to estimate effect sizes of mindfulness-based stress reduction (MBSR) in a sample of patients suffering from migraine. Method: Migraine patients (n = 62, mean age 44 years, 92% female) were randomly allocated to either MBSR or an active control intervention based on progressive muscle relaxation and psychoeducation. The primary outcome was the number of migraine days per month assessed by headache diaries covering one month before and one month after the intervention. Secondary outcomes included functional impairment, use of medication, psychological symptoms, quality of life, pain acceptance, pain self-efficacy, pain perception and self-attributed mindfulness. To measure feasibility, questionnaires assessing study compliance and contentment were administered. Results: The primary outcome migraine frequency showed no significant group difference. Compared to the control group, the MBSR group showed greater improvements in variables of psychological symptoms, pain self-efficacy and sensory pain perception. Within the MBSR condition, all variables showed significant improvements over the course span with effect sizes ranging from d = 0.37 to 0.81, apart from the primary outcome (27% reduction in migraine days, p = 0.07). Compliance and contentment rates were good, supporting the feasibility of the MBSR intervention. Conclusion: Overall, participants in the MBSR group showed more adaptive coping strategies and decreased levels of psychological impairment compared to the control group, indicating a reduced impact of migraine on their everyday lives. It is concluded that this feasibility study demonstrates the ability of mindfulness-based interventions to reduce suffering in patients with migraine.

Pain perception and functional/occlusal parameters in sleep bruxism subjects following a therapeutic intervention

BackgroundThis study was conducted to assess the individual pain perception in sleep bruxism (SB) subjects. Moreover, the effects of a cognitive behavioural therapy (CBT) compared to an occlusal appliance (OA) on pain perception and a possible continuative impact on several functional parameters were investigated.MethodsA total of 57 SB subjects participated in this investigation. The diagnosis of SB was based on the clinical criteria of the American Academy of Sleep Medicine (AASM). Twenty-eight SB subjects were randomly allocated to the CBT group and 29 to the OA group. The therapeutic intervention took place over a period of 12 weeks, whereby both groups were examined at baseline, immediately after termination of the intervention, and at a 6-month follow-up for pain perception and functional parameters. At each of the three measurement periods, participants completed the pain perception scale and ten functional/occlusal parameters were recorded.ResultsOf the 12 parameters recorded, statistically significant main effects were found for the affective pain perception (p < 0.05) and for the three functional variables. Interestingly, the values obtained for the affective pain perception were considerably below that of a reference group. Apart from the determined statistically significant results, the values recorded for all functional/occlusal variables as well as those obtained for the sensory pain perception were clearly located within normative ranges.ConclusionsWithin the limitations of this study, it might be concluded that the significantly reduced affective pain perception in SB subjects is the expression of an adaptation mechanism.

In Silico Prediction of the Anti-Depression Mechanism of a Herbal Formula (Tiansi Liquid) Containing Morinda officinalis and Cuscuta chinensis.

Purpose: Depression is a sickening psychiatric condition that is prevalent worldwide. To manage depression, the underlying modes of antidepressant effect of herbals are important to be explored for the development of natural drugs. Tiansi Liquid is a traditional Chinese medicine (TCM) that is prescribed for the management of depression, however its underlying mechanism of action is still uncertain. The purpose of this study was to systematically investigate the pharmacological mode of action of a herbal formula used in TCM for the treatment of depression. Methods: Based on literature search, an ingredients-targets database was developed for Tiansi Liquid, followed by the identification of targets related to depression. The interaction between these targets was evaluated on the basis of protein-protein interaction network constructed by STITCH and gene ontology (GO) enrichment analysis using ClueGO plugin. Results: As a result of literature search, 57 components in Tiansi Liquid formula and 106 potential targets of these ingredients were retrieved. A careful screening of these targets led to the identification of 42 potential targets associated with depression. Ultimately, 327 GO terms were found by analysis of gene functional annotation clusters and abundance value of these targets. Most of these terms were found to be closely related to depression. A significant number of protein targets such as IL10, MAPK1, PTGS2, AKT1, APOE, PPARA, MAPK1, MIF, NOS3 and TNF-α were found to be involved in the functioning of Tiansi Liquid against depression. Conclusions: The findings elaborate that Tiansi Liquid can be utilized to manage depression, however, multiple molecular mechanisms of action could be proposed for this effect. The observed core mechanisms could be the sensory perception of pain, regulation of lipid transport and lipopolysaccharide-mediated signaling pathway.