Sensitivity Of Nervous System Research Articles

Vestibular control of standing balance following 24h of sleep deprivation.

Sleep deprivation alters cognitive and sensorimotor function, but its effects on the control of standing balance are inconclusive. The vestibular system is critical for standing balance, and is modified by sleep deprivation; however, how sleep deprivation affects vestibular-evoked balance responses is unknown. Thus, this study aimed to examine the effect of 24h of sleep deprivation on the vestibular control of standing balance. During both a well-rested (i.e., control) and sleep deprivation condition, nine females completed two 90-s trials of bilateral, binaural stochastic electrical vestibular stimulation (EVS) and two 120-s trials of quiet stance on a force plate. Quiet stance performance was assessed by center of pressure displacement parameters. Mediolateral ground reaction force (ML force) and surface electromyography (EMG) of the right medial gastrocnemius (MG) were sampled simultaneously with the EVS signal to quantify vestibular control of balance within the frequency (gain and coherence) and time (cumulant density) domains. Twenty-four hours of sleep deprivation did not affect quiet stance performance. Sleep deprivation also had limited effect on EVS-MG EMG and EVS-ML Force coherence (less than control at 8-10.5Hz, greater at ~ 16Hz); however, gain of EVS-MG EMG (< 8, 11-24Hz) and EVS-ML force (0.5-9Hz) was greater for sleep deprivation than control. Sleep deprivation did not alter peak-to-peak amplitude of EVS-MG EMG (p = 0.51) or EVS-ML force (p = 0.06) cumulant density function responses. Despite no effect on quiet stance parameters, the observed increase in vestibular-evoked balance response gain suggests 24-h sleep deprivation may lead to greater sensitivity of the central nervous system when transforming vestibular-driven signals for standing balance control.

Peripheral and central pathogenesis of postherpetic neuralgia.

Postherpetic neuralgia (PHN) is a classic chronic condition with multiple signs of peripheral and central neuropathy. Unfortunately, the pathogenesis of PHN is not well defined, limiting clinical treatment and disease management. To describe the peripheral and central pathological axes of PHN, including peripheral nerve injury, inflammation induction, central nervous system sensitization, and brain functional and structural network activity. A bibliographic survey was carried out, selecting relevant articles that evaluated the characterization of the pathogenesis of PHN, including peripheral and central pathological axes. Currently, due to the complexity of the pathophysiological mechanisms of PHN and the incomplete understanding of the exact mechanism of neuralgia. It is essential to conduct in-depth research to clarify the origins of PHN pathogenesis and explore effective and comprehensive therapies for PHN.

Pain with orgasm in endometriosis: potential etiologic factors and clinical correlates.

Pelvic pain worsened by orgasm is a poorly understood symptom in patients with endometriosis. To assess the prevalence of pelvic pain worsened by orgasm in patients with endometriosis and explore its association with potential etiologic factors, including pelvic floor myalgia, uterine tenderness and adenomyosis, and central nervous system sensitization. An analysis was done of a prospective data registry based at a tertiary referral center for endometriosis. Eligible participants were patients aged 18 to 50 years who were referred between January 1, 2018, and December 31, 2019, diagnosed with endometriosis, and subsequently underwent surgery at the center. Clinical features were compared between participants reporting worsening pelvic pain with orgasm and those without worsening pain with orgasm, including patient-reported variables, physical examination findings, and anatomic phenotyping at the time of surgery. Pelvic floor myalgia and uterine tenderness were assessed by palpation on pelvic examination, adenomyosis by ultrasound, and central nervous system sensitization via the Central Sensitization Inventory (range, 0-100). Outcomes included pelvic or lower abdominal pain in the last 3months that worsened with orgasm (yes/no). Among 358 participants with endometriosis, 14% (49/358) reported pain worsened by orgasm while 86% (309/358) did not. Pain with orgasm was significantly associated with pelvic floor myalgia (55% [27/49] vs 35% [109/309]; Cohen's h = 0.40, P = .01) and higher scores on the Central Sensitization Inventory (mean ± SD, 53.3 ± 17.0 vs 42.7 ± 18.2; Cohen's d = 0.60, P < .001) but not with uterine tenderness or adenomyosis. Other clinical features associated with pain with orgasm were poorer sexual health (higher scores: deep dyspareunia, Cohen's h = 0.60; superficial dyspareunia, Cohen's h = 0.34; and Female Sexual Distress Scale-Revised, Cohen's d = 0.68; all P < .05) and poorer mental health (higher scores: Patient Health Questionnaire-9, 12.9 ± 6.7 vs 9.1 ± 6.3, Cohen's d = 0.59, P < .001; Generalized Anxiety Disorder-7, 9.4 ± 5.6 vs 6.8 ± 5.5, Cohen's d = 0.48, P = .002). Anatomic findings at the time of surgery did not significantly differ between the groups. Interventions targeting pelvic floor myalgia and central nervous system sensitization may help alleviate pain worsened by orgasm in patients with endometriosis. A strength is that pain worsened by orgasm was differentiated from dyspareunia. However, pain with orgasm was assessed by only a binary question (yes/no). Also, the study is limited to a single center, and there were limited data on sexual function. Pelvic pain exacerbated by orgasm in people with endometriosis may be related to concurrent pelvic floor myalgia and central sensitization.

Neuroinflammatory activation in sensory and motor regions of the cortex is related to sensorimotor function in individuals with low back pain maintained by nociplastic mechanisms: A preliminary proof-of-concept study.

Chronic pain involves communication between neural and immune systems. Recent data suggest localization of glial (brain immune cells) activation to the sensorimotor regions of the brain cortex (S1/M1) in chronic low back pain (LBP). As glia perform diverse functions that impact neural function, activation might contribute to sensorimotor changes, particularly in LBP maintained by increased nervous system sensitivity (i.e., nociplastic pain). This preliminary proof-of-concept study aimed to: (i) compare evidence of neuroinflammatory activation in S1/M1 between individuals with and without LBP (and between nociceptive and nociplastic LBP phenotypes), and (ii) evaluate relationships between neuroinflammatory activation and sensorimotor function. Simultaneous PET-fMRI measured neuroinflammatory activation in functionally defined S1/M1 in pain-free individuals (n = 8) and individuals with chronic LBP (n = 9; nociceptive: n = 4, nociplastic: n = 5). Regions of S1/M1 related to the back were identified using fMRI during motor tasks and thermal stimuli. Sensorimotor measures included single and paired-pulse transcranial magnetic stimulation (TMS) and quantitative sensory testing (QST). Sleep, depression, disability and pain questionnaires were administered. Neuroinflammatory activation was greater in the lower back cortical representation of S1/M1 of the nociplastic LBP group than both nociceptive LBP and pain-free groups. Neuroinflammatory activation in S1/M1 was positively correlated with sensitivity to hot (r = 0.52) and cold (r = 0.55) pain stimuli, poor sleep, depression, disability and BMI, and negatively correlated with intracortical facilitation (r = -0.41). This preliminary proof-of-concept study suggests that neuroinflammation in back regions of S1/M1 in individuals with nociplastic LBP could plausibly explain some characteristic features of this LBP phenotype. Neuroinflammatory activation localized to sensorimotor areas of the brain in individuals with nociplastic pain might contribute to changes in sensory and motor function and aspects of central sensitization. If cause-effect relationships are established in longitudinal studies, this may direct development of therapies that target neuroinflammatory activation.

Oxidative stress and neurological disorders: Therapeutic strategies and pharmacological intervention

Oxidative stress plays a significant role in cerebral biochemical dysfunction, contributing to the increased sensitivity of the central nervous system to reactive oxygen species (ROS)-mediated injury. It is characterized by an imbalance between the production of ROS and the antioxidant capacity of the cell, which results in a variety of pathological disorders and diseases, including neurological conditions such as Parkinson&amp;rsquo;s disease, Alzheimer&amp;rsquo;s disease, schizophrenia, bipolar disorder, and anxiety. In this review, we delve into the role of oxidative stress in neurodegenerative disorders. We conducted a comprehensive search across various databases, including Google Scholar, ScienceDirect, and PubMed, with a focus on literature published within the past decade. Our search utilized terms such as &amp;ldquo;oxidative stress and neurological disorders,&amp;rdquo; &amp;ldquo;pharmacological interventions for neurological disorders,&amp;rdquo; &amp;ldquo;oxidative stress, free radicals, and neurological disorders,&amp;rdquo; and &amp;ldquo;free radicals and neurological disorders. Our aim was to elucidate the relationship between oxidative stress and neurological disorders, as well as to summarize available therapies and pharmacological interventions for these conditions.

The Complexity of Neuropathic Pain and Central Sensitization: Exploring Mechanisms and Therapeutic Prospects.

Neuropathic pain is a common pain syndrome, which seriously affects the quality of life of patients. The mechanism of neuropathic pain is complex. Peripheral tissue injury can trigger peripheral sensitization; however, what really plays a key role is the sensitization of the central nervous system. Central sensitization is a key factor in the perception of chronic pain. Central sensitization refers to the increased sensitivity of the central nervous system to pain treatment, which is related to the change of the functional connection mode of the neural network. The current study aims to reveal the basic molecular mechanisms of central sensitization, including the involvement of P2 purine X4 receptor and brain-derived neurotrophic factor. In terms of treatment, although there are drugs and physical therapy, the accuracy of targeting is limited and the efficacy needs to be further improved. Future therapeutic strategies may involve the development of new drugs designed to specifically inhibit the central sensitization process. This article focuses on the effector molecules involved in central sensitization, aiming to elucidate the pathogenesis of neuropathic pain and provide a basis for the development of more effective treatment models.

Assessment of Multisensory Sensitivity May Assist With the Management of Children With Chronic Pain.

Chronic pain is a significant problem in adults; however, it can also be challenging to evaluate and manage effectively in pediatric and adolescent populations. Many theories implicate different factors that cause pain to become chronic, more severe, or more detrimental to function. There is emerging evidence for the role of generalized multisensory sensitivity (MSS) as a contributing factor to chronic pain in the adult population; however, similar evidence in the pediatric literature is lacking. Thus, the purpose of this case series is to highlight the clinical use of MSS assessment in children and adolescents with chronic pain to better phenotype and provide targeted treatment. In this case series, we reviewed 5 patients between 12 and 16 years of age who received evaluation for multifocal, chronic pain in a multidisciplinary pain clinic. During the initial consultations, we reviewed the medical records, completed a full medical history, performed a physical examination, and assessed for MSS. It is theorized that MSS is a marker of increased central nervous system sensitivity to sensory input that may also impact pain processing and, potentially, a poorer prognosis. Four patients with MSS appeared to benefit from the inclusion of additional therapies, such as desensitization and occupational therapy, which was in contrast to the patient without notable MSS. Based on anecdotal observation of these 5 cases, increased sensory hypersensitivity is 1 additional factor that may be used to delineate possible neurobiological mechanisms and aid in the treatment decision-making for this challenging population.

Pancreatic quantitative sensory testing to predict treatment response of endoscopic therapy or surgery for painful chronic pancreatitis with pancreatic duct obstruction: study protocol for an observational clinical trial

IntroductionTreatment for abdominal pain in patients with chronic pancreatitis (CP) remains challenging in the setting of central nervous system sensitisation, a phenomenon of remodelling and neuronal hyperexcitability resulting from persistent...

5-HT3a receptor contributes to neuropathic pain by regulating central sensitization in a rat with brachial plexus avulsion

PurposeAs a frequently occurring complication resulting from brachial plexus avulsion (BPA), neuropathic pain significantly impacts the quality of life of patients and places a substantial burden on their families. Recent reports have suggested that the 5-HT3a receptor may play a role in the development and regulation of neuropathic pain. The current study aimed to explore the involvement of the 5-HT3a receptor in neuropathic pain resulting from BPA in rats. MethodsA rat model of neuropathic pain was induced through brachial plexus avulsion (BPA). The pain thresholds of the rats were measured after BPA. The spinal dorsal horn (SDH) of rats was collected at day 14 after surgery, and the expression and distribution of the 5-HT3a receptor were analyzed using immunohistochemistry and western blotting. The expression levels of various factors related to central sensitization were measured by western blot, including c-Fos, GFAP, IBA-1, IL-1β and TNF-α. The effects of 5-HT3a receptor antagonists on hyperalgesia were assessed through behavioral tests after intrathecal administration of ondansetron. Additionally, at 120 min postinjection, the SDH of rats was acquired, and the change of expression levels of protiens related to central sensitization were measured by western blot. ResultsBPA induced mechanical and cold hypersensitivity in rats. The 5-HT3a receptor was increased and mainly distributed on neurons and microglia in the SDH after BPA, and the level of central sensitization and expression of inflammatory factors, such as c-Fos, GFAP, IBA-1, IL-1β and TNF-α, were also increased markedly. Ondansetron, which is a selective 5-HT3a receptor antagonist, reversed the behavioral changes caused by BPA. The antagonist also decreased the expression of central sensitization markers and inflammatory factors. ConclusionThe results suggested that the 5-HT3a receptor is involved in neuropathic pain by regulating central nervous system sensitization in a rat brachial plexus avulsion model. Targeting the 5-HT3a receptor may be a promising approach for treating neuropathic pain after brachial plexus avulsion.

Pharmacologically Altering the Minds of the Old, Sick, and Dying

The percentage of the world’s population that falls into the category of “_elderly_” has increased and is expected to greatly increase in the upcoming decades. The burden for the physical and mental well-being of the elderly has largely fallen upon health professionals and caregivers in various living environments. This article reviews and discusses the common use of psychotropic drugs among elderly populations worldwide despite the increased sensitivity of the aged central nervous system to the effects of these drugs, and the greatly increased risk for falls, fractures, fainting, and hospital admission for adverse events due to the usage of psychotropic drugs in this age sector. _Psychotropic Polypharmacy, Potentially Inappropriate Medication_, and the mind-altering effects of psychotropic drugs in the elderly population are also explained. Finally, we discuss the near-universal usage of psychotropic drugs in _end-of-life protocols_ used in palliative care, hospice, and end-of-life treatment centers.

Differed spontaneous dissociative symptoms following the use of esketamine intranasal spray in a patient suffering from treatment-resistant depression: a case report.

Intranasal esketamine is used in France for treatment-resistant depression. Dissociative symptoms are common side effects during treatment sessions. We report a case of delayed spontaneous dissociative symptoms following esketamine administration. A 20-year-old female with treatment-resistant depression received esketamine treatment. Dissociative symptoms occurred during sessions and persisted at a distance, often accompanied by anxiety. Delayed dissociative phenomena disappeared within the fourth week of treatment by esketamine. The literature mainly discusses dissociation during esketamine treatment sessions, with limited data on differed spontaneous episodes. Three hypotheses are discussed concerning the mechanism of occurrence of these dissociative phenomena, including esketamine's direct effect, central nervous system sensitization, and anxiety-induced dissociation. We present the first case of differed spontaneous dissociative effects after intranasal esketamine administration for treatment-resistant depression. Our main hypothesis suggests that esketamine may act as a 'pattern' for dissociative experiences, heightening the patient's ability to discern these phenomena during other instances of dissociation, such as acute anxiety attacks. Further research is needed to validate this hypothesis.

Mental Health Outcomes of Endometriosis Patients during the COVID-19 Pandemic: Impact of Pre-pandemic Central Nervous System Sensitization

To correlate pain-related phenotyping for central nervous system sensitization in endometriosis-associated pain with mental health outcomes during the COVID-19 pandemic, the prospective Endometriosis and Pelvic Pain Interdisciplinary Cohort (ClinicalTrials.gov #NCT02911090) was linked to the COVID-19 Rapid Evidence Study of a Provincial Population-Based Cohort for Gender and Sex (RESPPONSE) dataset. The primary outcomes were depression (PHQ-9) and anxiety (GAD-7) scores during the pandemic. The explanatory variables of interest were the Central Sensitization Inventory (CSI) score (0–100) and endometriosis-associated chronic pain comorbidities/psychological variables before the pandemic. The explanatory and response variables were assessed for correlation, followed by multivariable regression analyses adjusting for PHQ-9 and GAD-7 scores pre-pandemic as well as age, body mass index, and parity. A higher CSI score and a greater number of chronic pain comorbidities before the pandemic were both positively correlated with PHQ-9 and GAD-7 scores during the pandemic. These associations remained significant in adjusted analyses. Increasing the CSI score by 10 was associated with an increase in pandemic PHQ-9 by .74 points (P < .0001) and GAD-7 by .73 points (P < .0001) on average. Each additional chronic pain comorbidity/psychological variable was associated with an increase in pandemic PHQ-9 by an average of .63 points (P = .0004) and GAD-7 by .53 points (P = .0002). Endometriosis patients with a history of central sensitization before the pandemic had worse mental health outcomes during the COVID-19 pandemic. As a risk factor for mental health symptoms in the face of major stressors, clinical proxies for central sensitization can be used to identify endometriosis patients who may need additional support. PerspectiveThis article adds to the growing literature of the clinical importance of central sensitization in endometriosis patients, who had more symptoms of depression and anxiety during the COVID-19 pandemic. Clinical features of central sensitization may help clinicians identify endometriosis patients needing additional support when facing major stressors.

Australian healthcare professionals' beliefs and practice behaviours in management of chronic pelvic pain: a cross-sectional survey.

Background Chronic pelvic pain (CPP) is a common and debilitating condition, and sufferers present to healthcare professionals with variable complex symptoms and co-morbidities. This study aimed to investigate the current beliefs and practice behaviours of healthcare professionals towards the management of CPP in Australian females. Methods We distributed an online survey to Australian healthcare professionals. Participants were questioned regarding their beliefs, the importance of various contributing factors and assessment variables, and their management preferences for two CPP vignettes. Demographic information and responses were analysed with descriptive statistics. Results Complete data were obtained and analysed from 446 respondents including gynaecologists (n =75), general practitioners (GPs) (n =184) and physiotherapists (n =187). Most of the respondents were female (88.1%), with male (11.7%) and other (0.2%) making up a smaller representation. Physiotherapists rated themselves higher in understanding mechanisms of CPP (64.7% very good to excellent) compared to gynaecologists (41.3%) and GPs (22.8%). Physiotherapists also reported higher levels of confidence in managing patients with CPP (57.8% quite or extremely confident) compared to 41.3% of gynaecologists and 22.3% of GPs who reported being quite or extremely confident. All three professions rated patient's beliefs (89.8%), nervous system sensitisation (85.7%), stress/anxiety/depression (91.9%), fear avoidance (83.3%), history of sexual/emotional/physical abuse (94.1%) and pelvic floor muscle function (85.0%) as very/extremely important factors in the development of chronic pelvic pain. Most gynaecologists (71.0%) and GPs (70.2%) always referred for pelvic ultrasound during assessment. Physiotherapists assessed goal setting (88.8%) and screened for patients' beliefs (80.9%) more often than gynaecologists (30.4% and 39.1% respectively) and GPs (46.5% and 29.0% respectively). Conclusions All three groups of healthcare professionals demonstrated a good understanding of pain mechanisms and incorporated a biopsychosocial and multidisciplinary approach to management of females with chronic pelvic pain. However, both gynaecologists and GPs were less confident in their understanding of and management of CPP, and less likely to consider patient beliefs and goals. The findings of this online survey may assist in the provision of more targeted education to further improve management of this condition.

Ab. No. 16 Exercises and Pain Education Improves Clinical Outcomes in a Subgroup of Patients With Chronic Low Back Pain Positive for Central Sensitization

Introduction: Exercises have been found to decrease pain and the overall sensitivity of the central nervous system through the activation of exercise-induced endogenous analgesia and spinal inhibitory mechanisms. Despite the recommendations of many reviews that exercise programs reduce pain and disability in persons with chronic pain, the overall confidence is considered ‘critically low’. This study aimed to evaluate the effect of different exercises (aerobic, motor control, and superficial strengthening) relative to patient education on pain sensitivity and clinical outcomes in patients with chronic non-specific low back pain (NSCLBP) positive for central sensitization. Methods: The trial is a randomized controlled study with concealed allocation and blinding of assessors with four experimental groups (n=172) and one healthy control group (n=43). Participants were engaged in moderately intense treadmill walking sessions, activities for trunk stabilization, and strengthening exercises for the trunk and abdominal muscles along with patient education as per their group allocation. The control group received only patient education. The primary outcome was the cold pressor test. The secondary outcomes were pain intensity, disability, letter-number sequencing subtest, Stroop neurophysiological test, quality of life, and isometric muscle strength of the spine and hip muscles. Measures were taken at baseline and 12 and 24 weeks. Result: The results showed that patients with CLBP exhibit impaired CPM relative to healthy volunteers even after the intervention period. The overall results of the study showed improvement with time, and there was no difference between the groups in improving outcomes (p &gt; 0.05). There was a small effect size in favor of groups that received exercise and patient education (&lt;0.15) over the control group. Conclusion: Considering the comparable effects on clinical outcomes in patients with NSCLBP, this population may be encouraged to undertake exercises of moderate intensity of their preference.

Upregulation of KDM6B in the anterior cingulate cortex contributes to neonatal maternal deprivation-induced chronic visceral pain in mice.

Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disease characterized by chronic visceral pain with a complex etiology and challenging treatment. Although accumulating evidence supports the involvement of central nervous system sensitization in the development of visceral pain, the precise molecular mechanisms remain incompletely understood. In this study, we highlight the critical regulatory role of lysine-specific demethylase 6B (KDM6B) in the anterior cingulate cortex (ACC) in chronic visceral pain. To simulate clinical IBS conditions, we utilized the neonatal maternal deprivation (NMD) mouse model. Our results demonstrated that NMD induced chronic visceral pain and anxiety-like behaviors in mice. Notably, the protein expression level of KDM6B significantly increased in the ACC of NMD mice, leading to a reduction in the expression level of H32K7me3. Immunofluorescence staining revealed that KDM6B primarily co-localizes with neurons in the ACC, with minimal presence in microglia and astrocytes. Injecting GSK-J4 (a KDM6B-specific inhibitor) into ACC of NMD mice, resulted in a significant alleviation in chronic visceral pain and anxiety-like behaviors, as well as a remarkable reduction in NR2B expression level. ChIP assay further indicated that KDM6B regulates NR2B expression by influencing the demethylation of H3K27me3. In summary, our findings underscore the critical role of KDM6B in regulating chronic visceral pain and anxiety-like behaviors in NMD mice. These insights provide a basis for further understanding the molecular pathways involved in IBS and may pave the way for targeted therapeutic interventions.

The Prokineticin System in Inflammatory Bowel Diseases: A Clinical and Preclinical Overview.

Inflammatory bowel disease (IBD) includes Crohn's disease (CD) and ulcerative colitis (UC), which are characterized by chronic inflammation of the gastrointestinal (GI) tract. IBDs clinical manifestations are heterogeneous and characterized by a chronic relapsing-remitting course. Typical gastrointestinal signs and symptoms include diarrhea, GI bleeding, weight loss, and abdominal pain. Moreover, the presence of pain often manifests in the remitting disease phase. As a result, patients report a further reduction in life quality. Despite the scientific advances implemented in the last two decades and the therapies aimed at inducing or maintaining IBDs in a remissive condition, to date, their pathophysiology still remains unknown. In this scenario, the importance of identifying a common and effective therapeutic target for both digestive symptoms and pain remains a priority. Recent clinical and preclinical studies have reported the prokineticin system (PKS) as an emerging therapeutic target for IBDs. PKS alterations are likely to play a role in IBDs at multiple levels, such as in intestinal motility, local inflammation, ulceration processes, localized abdominal and visceral pain, as well as central nervous system sensitization, leading to the development of chronic and widespread pain. This narrative review summarized the evidence about the involvement of the PKS in IBD and discussed its potential as a druggable target.

Exploring different models of pain phenotypes and their association with pain worsening in people with early knee osteoarthritis: The MOST cohort study

To determine i) pain phenotypes (PP) in people with early-stage knee osteoarthritis (EKOA); ii) the longitudinal association between the phenotypes and pain worsening at two years. We studied participants with EKOA from the Multicenter Osteoarthritis Study defined as pain intensity ≤3/10, Kellgren and Lawrence grade ≤2, intermittent pain none to sometimes, and no constant pain. Two models of PP were explored. Model A included pressure pain thresholds, temporal summation, conditioned pain modulation, pain catastrophizing, sleep quality, depression, and widespread pain (WSP). In Model B, gait characteristics, quadriceps strength, comorbidities, and magnetic resonance imaging features were added to Model A. Latent Class Analysis was used to create phenotypes, and logistic regression was used to determine their association with pain worsening. 750 individuals (60% females), mean age [standard deviation (SD)]: 60.3 (9.4) were included in Model A and 333 individuals (60% females), mean age (SD): 59.4 (8.1) in Model B. 3-class and 4-class solutions were chosen for Model A and Model B. In Model A, the most "severe" phenotype was dominated by psychosocial factors, WSP, and measures of nervous system sensitization. Similarly in Model B, the Model A phenotype plus gait variables, quadriceps strength, and comorbidities were dominant. Surprisingly, none of the phenotypes in either model had a significant relationship with pain worsening. Phenotypes based upon various factors thought to be important for the pain experience were identified in those with EKOA but were not significantly related to pain worsening. These phenotypes require validation with clinically relevant endpoints.

Rapid cold hardening modifies ion regulation to delay anoxia-induced spreading depolarization in the CNS of the locust

Insects experience different kinds of environmental stresses that can impair neural performance, leading to spreading depolarization (SD) of nerve cells and neural shutdown underlying coma. SD is associated with a sudden loss of ion, notably K+, homeostasis in the central nervous system. The sensitivity of an insect's nervous system to stress (e.g., anoxia) can be modulated by acute pre-treatment. Rapid cold hardening (RCH) is a form of preconditioning, in which a brief exposure to low temperature can enhance the stress tolerance of insects. We used a pharmacological approach to investigate whether RCH affects anoxia-induced SD in the locust, Locusta migratoria, via one or more of the following homeostatic mechanisms: (1) Na+/K+-ATPase (NKA), (2) Na+/K+/2Cl− co-transporter (NKCC), and (3) voltage-gated K+ (Kv) channels. We also assessed abundance and phosphorylation of NKCC using immunoblotting. We found that inhibition of NKA or Kv channels delayed the onset of anoxia-induced SD in both control and RCH preparations. However, NKCC inhibition preferentially abrogated the effect of RCH. Additionally, we observed a higher abundance of NKCC in RCH preps but no statistical difference in its phosphorylation level, indicating the involvement of NKCC expression or degradation as part of the RCH mechanism.

Systematic review and meta-analysis of calculating degree of comorbidity of irritable bowel syndrome with migraine

BackgroundIrritable bowel syndrome (IBS) and migraines are often comorbid each other. These disorders are likely to be bidirectionally linked through the gut-brain axis and share several underlying mechanisms including central nervous system sensitization. However, quantitative analysis of comorbidity was not reported enough. The aim of this systematic review and meta-analysis was to calculate the present degree of comorbidity of these two disorders.MethodsA literature search was performed searching for articles describing IBS or migraine patients with the same inverse comorbidity. Pooled odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs) were then extracted. The total effect estimates were determined and presented by random effect forest plots for the group of articles with IBS patients with migraine and the group of articles on migraine sufferers with comorbid IBS separately. The average results of these plots were compared.ResultsThe literature search resulted in initial 358 articles and final 22 articles for the meta-analysis. The total OR values obtained were 2.09 [1.79 – 2.43] in IBS with comorbid migraine or headache, 2.51 [1.76 – 3.58] for migraineurs with comorbid IBS and an overall HR of 1 .62 [1.29 – 2.03] was found for cohort studies of migraine sufferers with comorbid IBS. A similar expression of a selection of other comorbidities was found in IBS and migraine patients, especially for depression and fibromyalgia a strong similarity was found in their expression rate.ConclusionsThis systematic review with meta-analysis was the first to combine data on IBS patients with comorbid migraine and migraineurs with comorbid IBS. The fact that closely related existential rates were observed between these two groups should be used as motivation for future research to further investigate these disorders for why this similarity occurs. Mechanisms involved in central hypersensitivity such as genetic risk factors, mitochondrial dysfunction and microbiota are particularly good candidates. Experimental designs in which therapeutic methods for these conditions can be exchanged or combined may also lead to the discovery of more efficient treatment methods.

ID: 207032 Durability of Relief Following 60-day Percutaneous Medial Branch PNS Treatment for Chronic Low Back Pain

For patients with chronic axial low back pain (LBP), there is often clinical evidence of central nervous system sensitization and finding a clear source of nociceptive input or damage to the somatosensory system can be challenging. Conventional therapies that mask the pain can fail to address centrally-mediated, underlying causes of pain. Sixty-day percutaneous peripheral nerve stimulation (PNS) applied to medial branch nerves offers a non-opioid, non-destructive, and non-surgical treatment designed to restore the balance of peripheral inputs to the central nervous system and reverse maladaptive changes in central pain processing, which can be applied earlier in the treatment continuum than permanently-implanted neurostimulation systems. The objective of this large multicenter clinical trial was to characterize the responses to medial branch PNS in a prospective multicenter case series study in patients recalcitrant to multiple non-surgical treatments. Additional goals of the clinical trial were to determine which low back pain patient phenotypes may be more or less likely to respond to PNS.