Central Sensitization Pain Research Articles

Characteristics of clusters with contrasting relationships between central sensitization-related symptoms and pain

The central sensitization inventory (CSI) evaluates the central sensitization (CS)-related symptoms associated with increased pain sensitivity. However, the CSI includes items that are not directly related to pain. In this study, 146 patients with pain were classified into subgroups by k-means cluster analysis based on the short form of the central sensitization inventory (CSI9) and pain scores. In addition, inter-group and multiple comparisons were performed to examine the characteristics of each group. As a result of this study, there were three subgroups (clusters 1, 2, and 3) in which the CSI9 and pain intensity were both low, moderate, and high, and one subgroup (cluster 4) in which only CSI9 was high and pain intensity was low. Two subgroups with high CSI9 scores but contrasting pain intensities (clusters 3 and 4) were extracted; the pattern of CS-related symptoms in these two groups was very similar, with no differences in most of the non-pain factors. It is necessary to consider these points when interpreting the clinical condition of a patient with pain when using the assessment of CS-related symptoms.

End-range Maitland mobilization decreasing pain sensitivity in knee osteoarthritis: randomized, controlled clinical trial.

Pressure pain threshold (PPT) is a widely applied method for measuring the magnitude of increased peripheral and central pain sensitivity causing hyperalgesia in knee osteoarthritis (OA). Although manual therapy techniques effects positively PPT, the effect of end-range Maitland mobilization has not been evaluated in knee OA. The aim of this study was to investigate the effect of end-range Maitland mobilization compared to sham manual therapy technique on PPT and function-related measures. The design of the study was of a randomized, controlled clinical trial. Outpatient setting. Forty women with moderate-to-severe knee OA. Twenty patients (N.=20) were randomly assigned to Maitland group (MG) and twenty patients (N.=20) to control group (CG). Patients in MG received single end-range Maitland mobilization while patients in CG received sham manual therapy technique. Assessment was performed at baseline, 30 minutes and after 1-week period. Outcome measures were PPT locally at knee and distant at ipsilateral extensor carpi radialis longus muscle, general pain during the previous week using the Visual Analogue Scale (VAS), Timed Up and Go Test (TUG) time associated with pain measured with Numerating Pain Rating Scale (NPRS) and strength of passive resistance of knee at onset of pain. Despite all outcome measures improved significantly postintervention, no changes were detected after 1-week period compared to postintervention in MG. No change of outcome measures was found also postintervention and after 1-week period compared to postintervention in CG. All postintervention results showed significant improvement in between-group comparison in favor of MG. However, after 1-week period, only strength of passive resistance revealed significant difference in between-group comparison in favor of MG (P<0.001). Although end-range Maitland mobilization has an immediate effect on decreasing peripheral and central pain sensitivity and improving function-related measures in knee OA, these changes may not cause clinically relevant effect based on data measured after 1-week period. Investigating the time-course of end-range Maitland mobilization for determining the optimal treatment frequency during rehabilitation is suggested in knee OA.

Human assumed central sensitisation (HACS) in patients with chronic low back pain radiating to the leg (CLaSSICO study)

IntroductionPatients with chronic low back pain radiating to the leg (CLBPr) are sometimes referred to a specialised pain clinic for a precise diagnosis based, for example, on a diagnostic selective...

Pain Tolerance Self-Assessment vs Objective Pressure Sensitivity: Do Patients Accurately Estimate Their Own Pain Tolerance?

Category:Basic Sciences/Biologics; OtherIntroduction/Purpose:Effective pain treatment remains elusive in the orthopedic foot and ankle practice as evidenced by the variable experience of pain, post-operative or otherwise. Intrinsic pain tolerance is likely contributing to this variability in the patient's experience of pain. Pressure dolorimetry is a validated, objective measure to assess pressure sensitivity and is correlated with pain tolerance. No previous study in the orthopedic foot and ankle literature has attempted to correlate objective versus subjective pain tolerance. General mental health is associated with central pain sensitization and may also affect pain tolerance. Our hypothesis was that subjective self-assessment of pain tolerance would be correlated with objective dolorimetry. We hypothesized that mental patient-reported outcome scores would also be correlated to objective pain tolerance.Methods:Prospectively-collected patient-reported outcome scores (PROMIS), dolorimetry measurements, and survey data of subjective reported pain tolerance were collected pre-operatively on 50 consecutive patients by two surgeons in an urban orthopedic foot and ankle practice. Patients were included if they had normal sensation on the plantar foot and no prior surgery or plantar heel source of pain. Each patient underwent objective measurement of their ability to withstand pressure applied to the plantar heel causing 5/10 pain using a hand-held dolorimeter with digital pressure measurement display. Each patient was administered a preoperative battery of PROMIS physical function (PF), pain interference (PI), and mood/depression (M) instruments, and a separate survey where they scaled their subjective tolerance to pain and discomfort. Statistical analysis was performed utilizing students t-test for continuous variables. Correlations were evaluated with Pearson's R coefficient. Data are reported as means (+/- standard deviation) unless otherwise noted.Results:50 patients received hand-held dolorimetry measurements, completed the pain tolerance survey, and completed PROMIS measures. Dolorimetry data from the plantar heel was normally distributed with mean force 24 N/cm2 (+/-10) to reflect a 5/10 pain experienced by the patient. Patients were shown to estimate their pain threshold with mean subjective pain threshold 6.8/10 (+/-2) regardless of objective pain data or PROMIS scores. The mean PROMIS scores of the sample were PF (41+/-8), PI (60+/-7), and M (49+/-9) reflecting a sample with decreased physical function and increased pain which could be expected in an outpatient foot and ankle clinic. There was a negative correlation of R=(-0.432) regarding PROMIS-M with dolorimetry objective pain tolerance which was statistically significant (p<-0.05). Patients had more features of depression/anxiety (PROMIS-M score >60) had a statistically significant decrease in pain threshold to 18+/-8 N/cm2 compared to 30 +/- 9 N/cm2 for those who were less depressed (p<0.01)).Conclusion:Subjective self assessment of pain tolerance is not well correlated to objective pain threshold data or other markers of mental health, and should not influence medical decision-making. Features of depression on PROMIS-M are associated with an objectively lower pain threshold which is in agreement with prior findings of central pain sensitization in patients with depression and anxiety in other studies. Future work is required to correlate dolorimetry data with post-operative medication utilization, and patient-reported outcome measures after surgery.

Short- and long-term effects of whole-body photobiomodulation on pain, functionality, tissue quality, central sensitisation and psychological factors in a population suffering from fibromyalgia: protocol for a triple-blinded randomised clinical trial.

Background:The development of an integral and global treatment to improve the quality of life in those with fibromyalgia syndrome (FMS) is challenging. The aim of this study is to investigate the impact of whole-body photobiomodulation (PBM) on pain perception, functionality, quality of soft tissue, central sensitisation and psychological factors in patients suffering with FMS.Methods:This study is a randomised, placebo-controlled clinical trial. A total of 44 participants will be recruited in a private care practice and randomised to receive either a whole-body PBM therapy programme or placebo in the same care centre. The parameters of the PBM programme are as follows: wavelengths of red and near-infrared LEDs 50:50 ratio with 660–850 nanometers; fluence of 25.2 J/cm2; treatment time of 1200 s and a total power emitted of 967 W. Treatment sessions will be 3 times weekly for a period of 4 weeks, totalling 12 treatment sessions. Primary outcome will be pain (Numeric Pain Rating Scale; Widespread Pain Index; Symptom Severity Score). Secondary outcomes will be functionality (Fibromyalgia Impact Questionnaire; the Leisure Time Physical Activity Instrument), quality of soft tissue (elastography), central sensitisation (pain pressure threshold and the Autonomic Symptom Profile) and psychological factors (Pain Catastrophising scale, Tampa Scale, Self-Efficacy questionnaire). Assessments will be at baseline (T1), after session 6 (T2), after treatment (T3) and 2 weeks (T4), 3 (T5) and 6 (T6) month follow-up.Discussion:PBM therapy has been shown to reduce pain and inflammation and to increase the rate of tissue repair for a wide range of conditions, but its potential use as a whole-body treatment in FM is yet to be explored. This trial will investigate whether whole-body PBM therapy is effective at reducing pain intensity, improving functionality, quality of soft tissue, central sensitisation symptoms and psychological measurements. Furthermore, 3- and 6-month follow-up will investigate long-term efficacy of this treatment.Trial registration:NCT04248972. Registered on January 29, 2020, https://clinicaltrials.gov/ct2/show/NCT04248972?term=navarro-ledesma+santiago&draw=2&rank=2.

A Narrative Review of Anatomy and Clinical Biopsychosocial Assessment of Sacroiliac Joint Pain

Sacroiliac Joint (SIJ) pain is a severe disorder that affects 15% to 25% of individuals having axially low back pain. The most common causes of depressive symptoms are fear of movement, pain catastrophising, stress, and nervous system sensitisation. Recent research has shown that radiological imaging, are inadequate for diagnosing SIJ pain. For immersive and patient centred experiences, a comprehensive professional Biopsychosocial (BPS) physiotherapy evaluation is suggested. A new biopsychosocial model has been proposed that acknowledges all critical health and disease factors and promotes the interaction of biological, psychological, and social influences, but moves further than a narrow perspective. Psychosocial influences on well-being have generated an interest in physician services, physiotherapy evaluation, and implementation in a more systematic approach to a patient. This method is used to determine the current pain mechanism (predominant nociceptive, neuropathic, or non neuropathic central sensitisation pain) as well as the underlying pain mechanism. Patient’s biopsychosocial variables can establish and maintain SI discomfort. For a better plan of therapy to manage SIJ dysfunction, the biopsychosocial clinical assessment takes precedence over the examination of sacroiliac joint discomfort alone.

Generalized pain hypersensitivity and associated factors in gout.

ObjectivesPrevious studies have indicated that a sizeable proportion of patients with inflammatory arthritis present with features characteristic of central pain sensitization. However, this has not yet been examined in patients with gout. The objective of this study was to explore the presence of generalized pain hypersensitivity and associated factors in patients with diagnosed gout.MethodsA cross-sectional survey was performed in outpatients with crystal proven gout using the generalized pain questionnaire (GPQ) to screen for the presence of generalized pain hypersensitivity. Additional self-reported socio-demographic and medical information was collected and several patient-reported outcome measures were completed. Univariable logistic regressions and multivariable LASSO regression analysis with 10-fold cross-validation was used to explore relationships with patient characteristics, clinical features and PROMs.ResultsOf the 97 included patients (84.5% male; mean (s.d.) age: 68.9 ± 11.9 years), 20 patients (20.6%, 95% CI: 13.0, 30.0) reported possible generalized pain hypersensitivity defined as a GPQ score ≥11 (range: 0–28; mean (s.d.) GPQ: 6.3 ± 5.3). Lower age, concomitant fibromyalgia and more experienced difficulties in performing their social role were independently associated with generalized pain hypersensitivity. Notably, use of urate lowering therapy was significantly lower in those with generalized pain hypersensitivity.ConclusionsGeneralized pain hypersensitivity appears to be quite common in gout, despite its more intermittent nature compared with other inflammatory arthritides. As this kind of pain does not respond well to regular treatment, screening for non-inflammatory pain may be important for improving pain management in gout.

Characteristics, mechanism, and management of pain in atopic dermatitis: A literature review.

BackgroundAtopic dermatitis (AD) is a chronic, pruritic, immune‐mediated inflammatory disease. Developments in basic science and clinical research have increased our understanding of AD. Although pain as a symptom of AD is underemphasized in previous studies, multiple researchers address pain as a frequent burden of AD. However, the exact role of pain in AD is not fully understood.AimsOur review aimed to summarize the current evidence focusing on characteristics, mechanism, and management of pain in AD.Materials & MethodsWe conducted a thorough literature review in the PubMed database to figure out different aspects discussing pain in AD, including pain symptoms, burden, the relationship between pain and itch, mechanism, and pain management in AD.Results and ConclusionAD patients affected by skin pain vary from 42.7%‐92.2% with remarkable intensity and heavy burden. Skin pain and itch interacted both in symptoms and mechanisms. Atopic skin with the impaired barrier, neurogenic inflammation mediators, peripheral and central sensitization of pain may possibly explain pain mechanism in AD. Future research is needed to clarify the commonality and disparity of pain and itch in AD in order to seek efficacious medications and treatment.

The Role of TNF-α in the Pathogenesis of Temporomandibular Disorders.

Temporomandibular disorder (TMD) is an oral dentofacial disease that is related to multiple factors such as disordered dental occlusion, emotional stress, and immune responses. In the past decades, tumor necrosis factor-alpha (TNF-α), a pleiotropic cytokine, has provided valuable insight into the pathogenesis of TMD, particularly in settings associated with inflammation. It is thought that TNF-α participates in the pathogenesis of TMD by triggering immune responses, deteriorating bone and cartilage, and mediating pain in the temporomandibular joint (TMJ). Initially, TNF-α plays the role of "master regulator" in the complex immune network by increasing or decreasing the production of other inflammatory cytokines. Then, the effects of TNF-α on cells, particularly on chondrocytes and synovial fibroblasts, result in pathologic cartilage degradation in TMD. Additionally, multiple downstream cytokines induced by TNF-α and neuropeptides can regulate central sensitization and inflammatory pain in TMD. Previous studies have also found some therapies target TMD by reducing the production of TNF-α or blocking TNF-α-induced pathways. All this evidence highlights the numerous associations between TNF-α and TMD; however, they are currently not fully understood and further investigations are still required for specific mechanisms and treatments targeting specific pathways. Therefore, in this review, we explored general mechanisms of TNF-α, with a focus on molecules in TNF-α-mediated pathways and their potential roles in TMD treatment. In view of the high clinical prevalence rate of TMD and damage to patients' QOL, this review provides adequate evidence for studying links between inflammation and TMD in further research and investigation.

Mechanisms of Peripheral and Central Pain Sensitization: Focus on Ocular Pain.

Persistent ocular pain caused by corneal inflammation and/or nerve injury is accompanied by significant alterations along the pain axis. Both primary sensory neurons in the trigeminal nerves and secondary neurons in the spinal trigeminal nucleus are subjected to profound morphological and functional changes, leading to peripheral and central pain sensitization. Several studies using animal models of inflammatory and neuropathic ocular pain have provided insight about the mechanisms involved in these maladaptive changes. Recently, the advent of new techniques such as optogenetics or genetic neuronal labelling has allowed the investigation of identified circuits involved in nociception, both at the spinal and trigeminal level. In this review, we will describe some of the mechanisms that contribute to the perception of ocular pain at the periphery and at the spinal trigeminal nucleus. Recent advances in the discovery of molecular and cellular mechanisms contributing to peripheral and central pain sensitization of the trigeminal pathways will be also presented.

Wnt/β-Catenin Pathway in Experimental Model of Fibromyalgia: Role of Hidrox®.

Fibromyalgia (FM) is a chronic condition characterized by persistent widespread pain that negatively affects the quality of life of patients. The WNT/β-catenin signaling pathway seems to be involved in central sensitization and different pain states. The objective of this study was to investigate the beneficial effects of a new compound called Hidrox® (HD), containing 40–50% hydroxytyrosol, in counteracting the pain associated with FM. An FM-like model was induced in rats by subcutaneous injections of reserpine (1 mg/kg) for three consecutive days. Later, HD (10 mg/kg) was administered orally to the animals for seven days. Reserpine injections induced WNT/β-catenin pathway activation, release of pro-inflammatory mediators as well as a significant increase in oxidative stress. Daily treatment with HD was able to modulate the WNT/β-catenin and Nrf2 pathways and consequently attenuate the behavioral deficits and microglia activation induced by reserpine injection. These results indicate that nutritional consumption of HD can be considered as a new therapeutic approach for human FM.

Segmental Chiropractic Spinal Manipulation Does not Reduce Pain Amplification and the Associated Pain-Related Brain Activity in a Capsaicin-Heat Pain Model.

Musculoskeletal injuries lead to sensitization of nociceptors and primary hyperalgesia (hypersensitivity to painful stimuli). This occurs with back injuries, which are associated with acute pain and increased pain sensitivity at the site of injury. In some cases, back pain persists and leads to central sensitization and chronic pain. Thus, reducing primary hyperalgesia to prevent central sensitization may limit the transition from acute to chronic back pain. It has been shown that spinal manipulation (SM) reduces experimental and clinical pain, but the effect of SM on primary hyperalgesia and hypersensitivity to painful stimuli remains unclear. The goal of the present study was to investigate the effect of SM on pain hypersensitivity using a capsaicin-heat pain model. Laser stimulation was used to evoke heat pain and the associated brain activity, which were measured to assess their modulation by SM. Eighty healthy participants were recruited and randomly assigned to one of the four experimental groups: inert cream and no intervention; capsaicin cream and no intervention; capsaicin cream and SM at T7; capsaicin cream and placebo. Inert or capsaicin cream (1%) was applied to the T9 area. SM or placebo were performed 25 min after cream application. A series of laser stimuli were delivered on the area of cream application (1) before cream application, (2) after cream application but before SM or placebo, and (3) after SM or placebo. Capsaicin cream induced a significant increase in laser pain (p < 0.001) and laser-evoked potential amplitude (p < 0.001). However, SM did not decrease the amplification of laser pain or laser-evoked potentials by capsaicin. These results indicate that segmental SM does not reduce pain hypersensitivity and the associated pain-related brain activity in a capsaicin-heat pain model.

Do "central sensitization" questionnaires reflect measures of nociceptive sensitization or psychological constructs? Protocol for a systematic review.

Central sensitization (CS) was first defined in animal studies to be increased nociceptive responsiveness due to sensitization of neurons in the central nervous system, usually the result of prolonged nociceptive input or a disease state. Recently, the concept of CS has been adopted in clinical assessments of chronic pain, but its diagnosis in humans has expanded to include the enhancement of a wide range of nociceptive, sensory, and emotional responses. Many poorly understood pain disorders are referred to as "central sensitivity syndrome," a term associated with a broad range of hypervigilant sensory and emotional responses. Diagnosis often involves a review of medical records and an assessment of behaviour, emotional disposition, and overall sensitivity of a patient. Obviously, these assessments are unable to directly capture the responsiveness of nociceptive neurons. The purpose of this review is to ascertain whether self-report questionnaires associated with central sensitization and the diagnosis of central sensitivity syndrome are associated with enhanced nociceptive responses or whether they more validly measure sensitivity in a broader sense (ie, including emotional responses). Following the PRISMA guidelines, a detailed search of studies that involve the Central Sensitization Inventory or Pain Sensitivity Questionnaire correlated with either nociceptive sensory tests (quantitative sensory testing) or emotional hypervigilance (anxiety, depression, stress, etc) will be conducted on MEDLINE, PsychINFO, and Web of Science. The review is expected to synthesize correlations between sensitivity questionnaires and nociceptive or emotional sensitivity to determine whether these questionnaires reflect a broadened understanding of the term "central sensitization."

Painful diabetic peripheral neuropathy: Role of oxidative stress and central sensitisation.

Diabetic peripheral neuropathy (DPN) occurs in about half of people with diabetes, of whom a quarter may develop chronic pain. Pain may remain for years yet be difficult to treat because the underlying mechanisms remain unclear. There is consensus that processing excessive glucose leads to oxidative stress, interfering with normal metabolism. In this narrative review, we argue that oxidative stress may also contribute to pain. We reviewed literature in PubMed published between January 2005 and August 2021. In diabetes, hyperglycaemia and associated production of reactive species can directly increase pain signalling and activate sensory neurons; or the effects can be indirect, mediated by mitochondrial damage and enhanced inflammation. Furthermore, pain processing in the central nervous system is compromised in painful DPN. This is implicated in central sensitisation and dysfunctional pain modulation. However, central pain modulatory function is understudied in diabetes. Future research is required to clarify whether central sensitisation and/or disturbances in central pain modulation contribute to painful DPN. Positive results would facilitate early detection and future treatment.

DNA Methylation Changes in Fibromyalgia Suggest the Role of the Immune-Inflammatory Response and Central Sensitization.

Fibromyalgia (FM) has been explained as a result of gene-environment interactions. The present study aims to verify DNA methylation differences in eleven candidate genome regions previously associated to FM, evaluating DNA methylation patterns as potential disease biomarkers. DNA methylation was analyzed through bisulfite sequencing, comparing 42 FM women and their 42 healthy sisters. The associations between the level of methylation in these regions were further explored through a network analysis. Lastly, a logistic regression model investigated the regions potentially associated with FM, when controlling for sociodemographic variables and depressive symptoms. The analysis highlighted significant differences in the GCSAML region methylation between patients and controls. Moreover, seventeen single CpGs, belonging to other genes, were significantly different, however, only one cytosine related to GCSAML survived the correction for multiple comparisons. The network structure of methylation sites was different for each group; GRM2 methylation represented a central node only for FM patients. Logistic regression revealed that depressive symptoms and DNA methylation in the GRM2 region were significantly associated with FM risk. Our study encourages better exploration of GCSAML and GRM2 functions and their possible role in FM affecting immune, inflammatory response, and central sensitization of pain.

Prokineticin 2 mediates peripheral and central sensitization of somatic pain

Prokineticin 2 (PK2) is a newly discovered chemokine, which participates in various physiological functions of the body by binding to receptors PKR1 and PKR2. PK signaling pathway is a newly discovered important regulatory pathway for the occurrence and maintenance of pain after tissue injury and nerve injury in recent years. It plays a key role in regulating injury-related nociceptive events and is a potential therapeutic target for many diseases. The activation of PKRs can induce pain sensation and participate in the sensitivity of pain receptors to different stimuli. The PK system (PKs and PKRs) is an important link involved in inflammation and pain transmission in immune cells. PK2 is involved in the regulation of pain perception by activating PKR1 and PKR2 on primary sensory neurons. In rat primary sensory neurons, PK2 also enhances gated ion channel current through the PKC signaling pathway, inhibits GABA-activated currents, and sensitizes purine nucleotide P2 receptor (P2X). This paper reviews the research progress of PK2 in physical pain. We hope to find new drugs for the treatment of inflammatory pain that target the PKs signaling pathway in future studies.

IS DISTRIBUTION OF PAIN RELATED WITH CENTRAL SENSITIZATION IN PATIENTS WITH LOWER LIMB OSTEOARTHRITIS?

Design: Cross-sectional study. Background: Osteoarthritis is one of the most common conditions in our society. A growing number of studies suggest the existence of central sensitization (CS) in a subgroup of osteoarthritic patients. One of the criteria included for the classification of CS pain is the expanded distribution of pain. As this criterion is a well-recognized sign of CS, a digital pain drawing (DPD) analysis would be useful to easily identify possible extended areas of pain distribution (PD) in patients with OA. Objective: To study the relationship between the percentage of distribution of pain in the lower limb for both knee and hip, in patients before hip or knee arthroplasty, and the Central Sensitization Inventory Questionnaire. Methods: Twenty women (mean [Formula: see text] years) with diagnosed chronic (over 3 months) knee ([Formula: see text]) and hip ([Formula: see text]) OA participated in the study, with intensity of pain from mild to severe, meaning pain [Formula: see text]/10 using the Numeric Pain Rating Scale (NPRS). The PD was analyzed via software created for this research, called “Pain Distribution Application”. Results: A statistically significant positive correlation between CSI and PD to the lower extremity OA (hip and knee) ([Formula: see text], [Formula: see text]) was found. The distribution of pain has a linear correlation with the results in CSI, of patients who tested positive for CS, i.e. with a score of [Formula: see text]. Conclusions: As the distribution of pain on the surface of the body (diffusion) increases, so does the score of people who test positive for CSI. Our results showed that calculating the distribution of pain with our application may have a utility as a CS screening tool. The PD threshold of 10% of the body area is an index for CS for chronic pain lower limb OA patients.

Spinal cord neural activity of patients with fibromyalgia and healthy controls during temporal summation of pain: an fMRI study.

The cause for the increased sensitivity of patients with fibromyalgia (FM) to painful stimuli is unclear but sensitization of dorsal horn spinal cord neurons has been suggested. There, critical changes of sensory information occur which depend on the plasticity of second-order neurons and descending pain modulation, including facilitation and inhibition. This study used repetitive stimuli that produce temporal-summation-of-second-pain (TSSP) and central sensitization, relevant mechanisms for patients with chronic pain. We examined spinal cord neural activation during TSSP in patients with FM and healthy controls (HC) and used its functional connectivity with several brainstem nuclei to model the observed blood-oxygen-level-dependent (BOLD) time-course with pain ratings. Sixteen HC and 14 FM participants received repetitive heat stimuli to the hand at 0.4 Hz to achieve TSSP during functional imaging with a 3 T-Philips Achieva MRI scanner. Stimuli were adjusted to each individual's pain sensitivity to achieve maximal pain ratings of 50 ± 10 on a numerical pain scale (0-100). Using a 16-channel neurovascular coil, multiple image series were obtained from the cervical spinal cord to the brainstem using single-shot turbo-spin echo sequences. During repetitive, sensitivity-adjusted heat stimuli, pain ratings of all subjects increased as predicted, consistent with TSSP. HC and FM participants had similar temporal patterns of spinal activation: initial BOLD increase followed by deactivation. Structural equation modeling showed that the observed spinal activity during TSSP was associated with more BOLD activity across/within the brainstem in FM subjects than HC, suggesting differences in pain modulation.NEW & NOTEWORTHY "Windup" and its behavioral correlate "temporal-summation-of-second pain" (TSSP) represent spinal cord mechanisms of pain augmentation associated with central sensitization and chronic pain. Fibromyalgia (FM) is a chronic pain disorder, where abnormal TSSP has been demonstrated. We used fMRI to study spinal cord and brainstem activation during TSSP. We characterized the time course of spinal cord and brainstem BOLD activity during TSSP which showed abnormal brainstem activity in patients with FM, possibly due to deficient pain modulation.

Practical guidelines for the treatment of chronic nonspecific low back pain and comorbid chronic insomnia: clinical observation

A clinical case of a patient with chronic nonspecific low back pain and comorbid chronic insomnia is described, and a modern approach to the management of this patient category is shown. So-called yellow flags - factors that contribute to the central sensitization of pain - lead to chronicity of LBP. In the presented clinical case we identified the most common "yellow flags”: insomnia, pain catastrophizing, restrictive ”pain” behavior, anxiety. In practice, they often ignore the aforementioned factors, determine only the presence of back pain and prescribe analgesic therapy, which does not allow for an effective result.Insomnia is prevalent among patients with LBP, occurring in 47-64% of cases. With the COVID-19 pandemic among the population, the incidence of insomnia, anxiety and depression has increased. To date, the identification and treatment of these disorders is particularly relevant in the management of patients with chronic nonspecific LBP.The patient was treated, which included non-drug and drug methods and complied with Russian and foreign clinical guidelines on the therapy of chronic nonspecific LBP and on the therapy of chronic insomnia. Non-drug treatment consisted of educational talks, recommendations on daily activity and sleep hygiene, cognitive-behavioral therapy, mindfulness, relaxation, and therapeutic gymnastics. The listed methods were aimed at reducing pain catastrophizing, physical and social activation of the patient. The nonsteroidal anti-inflammatory drug dexketoprofen was used as pharmacotherapy according to a step-by-step regimen. After 5 days of therapy pain relief was observed, after 3 months of therapy back pain regressed, sleep normalized, mood improved. This therapeutic approach showed its effectiveness and safety in the treatment of chronic nonspecific LBP and comorbid chronic insomnia.

Sex Differences In Central Inflammatory Pain Sensitization Are Associated With Differential Expression Of Glycine Receptors And Glp-1 At The Spinal Cord

Sex Differences In Central Inflammatory Pain Sensitization Are Associated With Differential Expression Of Glycine Receptors And Glp-1 At The Spinal Cord