Sensitivity Of Central Nervous System Research Articles

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.

Abstract CT202: CSFctDNA as a surrogate for tumor tissue DNA in BC pts with CNS metastases: First results from the Brainstorm program (Oncodistinct 006)

Abstract Background: Central nervous system (CNS) metastases display molecular alterations that differ from primary tumors and metastatic sites, which might confer special CNS sensitivity for targeted treatments. Brain biopsies are an invasive approach and liquid biopsies (LB) are therefore being investigated as a potential tool for detecting these molecular alterations in cerebrospinal fluid (CSF) ctDNA. Methods: The BrainStorm program (NCT04109131) is an international, prospective, interventional study aiming to build a large clinico-pathological database to investigate the development of CNS metastases: (A) before the diagnosis; (B) at diagnosis; and (C) after the diagnosis of CNS metastases. Molecular landscape of CSFctDNA was analyzed and explored as a surrogate for CNS tumor tissue DNA using large next-generation sequencing panels in tumor tissue and tumor-informed targeted gene panels in LB (OncoDEEP®/OncoFOLLOW®) for patients (pts) included in Part (B). Results: As of October 2023, CSF was available for 30 out of 67 pts included in Part (B) of the study and analyses were performed for 12 matched extra-CNS tumor, plasma and CSF samples. The 12 cases were derived from pts with breast cancer (BC) (luminal n=6; triple negative (TN) n=2; HER2-positive n=4) and among them 4 pts were diagnosed with leptomeningeal metastases (LM). CSFctDNA was detectable in 7 out of the 12 CSF samples (58%) and in 3 out of 4 pts with LM (75%). In pts with detectable CSFctDNA, detection rate for known pathogenic molecular alterations was 80% (Table 1). No safety concerns from lumbar puncture were identified. Conclusion: The use of CSFctDNA as a surrogate for tumor tissue DNA in CNS metastases appears to be a feasible and safe approach. Clinically actionable alterations have been identified in CSFctDNA of pts with BC. Further results will be presented at a later stage. TABLE 1: NAND Table 1: Pathogenic molecular alterations in matched tumor, plasma and CSF from pts with detectable CSFctDNA Tumor type Extra-CNS tumor tissue Plasma CSF TNBC PIK3Ca pH1047R PIK3Ca pH1047R PIK3Ca pH1047R Luminal BC PIK3Ca Q546R PIK3Ca Q546R PIK3Ca Q546R Luminal (LM) None KRAS pG13D None Luminal BC BRCA2 p.Y1655, PIK3CA pE545K BRCA2 pY1655, PIK3CA pE545K BRCA2 pY1655, PIK3CA pE545K TNBC (LM) None None None Luminal (LM) ESR1 D538G, PIK3CA H1047R ESR1 D538G, PIK3CA H1047R ESR1 D538G, PIK3CA H1047R HER2-positive BC ErbB2 amplification None None Citation Format: Nuria Kotecki, Diogo Martins-Branco, Guilherme Nader-Marta, Andrea Gombos, Philippe Barthelemy, Anthony Gonçalves, Edith Borcoman, Florian Clatot, Stéphane Holbrechts, Eleonora Stephane de Maio D’Esposito, Claire Cheymol, Vincent Vanhaudenarde, François Duhoux, Caroline Duhem, Paul Clement, Lore Decoster, Hannelore Denys, Florence Lefranc, Jean-Luc Canon, Joseph Gligorov, Luca Arecco, Nadège Kindt, Ahmad Awada. CSFctDNA as a surrogate for tumor tissue DNA in BC pts with CNS metastases: First results from the Brainstorm program (Oncodistinct 006) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT202.

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.

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.

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.

Pelvic pain comorbidities associated with quality of life after endometriosis surgery

After endometriosis surgery, pain can persist or recur in a subset of patients. A possible reason for persistent pain after surgery is central nervous system sensitization and associated pelvic pain comorbidities. Surgery addresses the peripheral component of endometriosis pain pathophysiology (by lesion removal) but may not treat this centralized pain. Therefore, endometriosis patients with pelvic pain comorbidities related to central sensitization may experience worse pain-related outcomes after surgery, such as lower pain-related quality of life. This study aimed to determine whether baseline (preoperative) pelvic pain comorbidities are associated with pain-related quality of life at follow-up after endometriosis surgery. This study used longitudinal prospective registry data from the Endometriosis Pelvic Pain Interdisciplinary Cohort at the BC Women's Centre for Pelvic Pain and Endometriosis. Participants were aged ≤50 years with confirmed or clinically suspected endometriosis, and underwent surgery (fertility-sparing or hysterectomy) for endometriosis pain. Participants completed the pain subscale of the Endometriosis Health Profile-30 quality of life questionnaire preoperatively and at follow-up (1-2 years). Linear regression was performed to measure the individual relationships between 7 pelvic pain comorbidities at baseline and follow-up Endometriosis Health Profile-30 score, controlling for baseline Endometriosis Health Profile-30 and type of surgery received. These baseline (preoperative) pelvic pain comorbidities included abdominal wall pain, pelvic floor myalgia, painful bladder syndrome, irritable bowel syndrome, Patient Health Questionnaire 9 depression score, Generalized Anxiety Disorder 7 score, and Pain Catastrophizing Scale score. Least absolute shrinkage and selection operator regression was then performed to select the most important variables associated with follow-up Endometriosis Health Profile-30 from 17 covariates (including the 7 pelvic pain comorbidities, baseline Endometriosis Health Profile-30 score, type of surgery, and other endometriosis-related factors such as stage and histologic confirmation of endometriosis). Using 1000 bootstrap samples, we estimated the coefficients and confidence intervals of the selected variables and generated a covariate importance rank. The study included 444 participants. The median follow-up time was 18 months. Pain-related quality of life (Endometriosis Health Profile-30) of the study population significantly improved at follow-up after surgery (P<.001). The following pelvic pain comorbidities were associated with lower quality of life (higher Endometriosis Health Profile-30 score) after surgery, controlling for baseline Endometriosis Health Profile-30 score and type of surgery (fertility-sparing vs hysterectomy): abdominal wall pain (P=.013), pelvic floor myalgia (P=.036), painful bladder syndrome (P=.022), Patient Health Questionnaire 9 score (P<.001), Generalized Anxiety Disorder 7 score (P<.001), and Pain Catastrophizing Scale score (P=.007). Irritable bowel syndrome was not significant (P=.70). Of the 17 covariates included for least absolute shrinkage and selection operator regression, 6 remained in the final model (lambda=3.136). These included 3 pelvic pain comorbidities that were associated with higher follow-up Endometriosis Health Profile-30 scores or worse quality of life: abdominal wall pain (β=3.19), pelvic floor myalgia (β=2.44), and Patient Health Questionnaire 9 depression score (β=0.49). The other 3 variables in the final model were baseline Endometriosis Health Profile-30 score, type of surgery, and histologic confirmation of endometriosis. Pelvic pain comorbidities present at baseline before surgery, which may reflect underlying central nervous system sensitization, are associated with lower pain-related quality of life after endometriosis surgery. Particularly important were depression and musculoskeletal/myofascial pain (abdominal wall pain and pelvic floor myalgia). Therefore, these pelvic pain comorbidities should be candidates for a formal prediction model of pain outcomes after endometriosis surgery.

Central sensitization and mental health outcomes of endometriosis patients during the COVID-19 pandemic

To determine whether central nervous system sensitization in patients with endometriosis was associated with worse mental health outcomes during the COVID-19 pandemic. Data were linked between two British Columbia databases: the prospective Endometriosis Pelvic Pain Interdisciplinary cohort (EPPIC) that phenotypes endometriosis patients; and the Rapid Evidence Study of a Provincial Population Based Cohort for Gender and Sex cohort (RESPPONSE) that follows mental health outcomes during the COVID-19 pandemic. The predictors were the Central Sensitization Inventory (CSI) score and central sensitivity syndrome (CSS) comorbidities at baseline from EPPIC. The primary outcomes were PHQ-9 (depression) and GAD-7 (anxiety) scores in Phase 1 of the pandemic from RESPPONSE. Bivariate and multivariable analyses were performed. There were N=329 subjects in the linked dataset. On bivariate analysis, more central sensitization at baseline (i.e. higher CSI scores and more CSS comorbidities) was strongly associated with worse mental health during the pandemic (i.e. higher PHQ-9 and GAD-7 scores). On multivariable regression, after controlling for baseline mental health measures, age, BMI, and parity, both the CSI score and the number of CSS comorbidities at baseline were associated with worse PHQ-9 (P <0.0001, P = 0.0075) and worse GAD-7 (P <0.0001, P = 0.0054) scores during the pandemic. Central nervous system sensitization was associated with worse mental health for endometriosis patients during the COVID-19 pandemic. Central sensitization may predict mental health outcomes in the face of a pandemic or other stressors.

Abnormal immune system response in the brain of women with Fibromyalgia after experimental endotoxin challenge

BackgroundThe pathophysiology of fibromyalgia (FM) is thought to include an overactive immune system, leading to central nervous system sensitization, allodynia, and hyperalgesia. We aimed to test this theory using an experimental immune system activation procedure and neuroimaging with magnetic resonance spectroscopic imaging (MRSI). MethodsTwelve women with FM and 13 healthy women (healthy controls; HC) received 0.3 or 0.4 ng/kg endotoxin and underwent MRSI before and after the infusion. Changes in brain levels of choline (CHO), myo-inositol (MI), N-Acetylaspartate (NAA), and MRSI-derived brain temperature were compared between groups and dosage levels using mixed analyses of variance. ResultsSignificant group-by-time interactions in brain temperature were found in the right thalamus. Post-hoc testing revealed that brain temperature increased by 0.55 °C in the right thalamus in FM (t(10) = -3.483, p = 0.006), but not in HCs (p > 0.05). Dose-by-time interactions revealed brain temperature increases in the right insula after 0.4 ng/kg (t(12) = -4.074, p = 0.002), but not after 0.3 ng/kg (p > 0.05). Dose-by-time interactions revealed decreased CHO in the right Rolandic operculum after 0.4 ng/kg endotoxin (t(13) = 3.242, p = 0.006) but not 0.3 ng/kg. In the left paracentral lobule, CHO decreased after 0.3 ng/kg (t(9) = 2.574, p = 0.030) but not 0.4 ng/kg. Dose-by-time interactions affected MI in several brain regions. MI increased after 0.3 ng/kg in the right Rolandic operculum (t(10) = -2.374, p = 0.039), left supplementary motor area (t(9) = -2.303, p = 0.047), and left occipital lobe (t(10) = -3.757, p = 0.004), with no changes after 0.4 ng/kg (p > 0.05). Group-by time interactions revealed decreased NAA in the left Rolandic operculum in FM (t(13) = 2.664, p = 0.019), but not in HCs (p > 0.05). A dose-by-time interaction showed decreased NAA in the left paracentral lobule after 0.3 ng/kg (t(9) = 3.071, p = 0.013) but not after 0.4 ng/kg (p > 0.05). In the combined sample, there was a main effect of time whereby NAA decreased in the left anterior cingulate (F[1,21] = 4.458, p = 0.047) and right parietal lobe (F[1,21] = 5.457, p = 0.029). ConclusionWe found temperature increases and NAA decreases in FM that were not seen in HCs, suggesting that FM patients may have abnormal immune responses in the brain. The 0.3 and 0.4 ng/kg had differential effects on brain temperature and metabolites, with neither dose effecting a stronger response overall. There is insufficient evidence provided by the study to determine whether FM involves abnormal central responses to low-level immune challenges.

The Use of Peppermint Oil in Gastroenterology.

For decades, mint has been used worldwide for its relieving effects against gastrointestinal disturbances. Peppermint is a perennial herb common in Europe and North America. The active ingredient of peppermint oil is menthol and has various gastroenterological and non-gastroenterological uses, especially in the context of functional gastrointestinal disorders (FGIDs). We conducted a literature search on the main medical databases for original articles, reviews, meta-analyses, randomized clinical trials, and case series using the following keywords and acronyms and their associations: peppermint oil, gastro-intestinal motility, irritable bowel syndrome, functional dyspepsia, gastrointestinal sensitivity and gastrointestinal endoscopy. Peppermint oil and its constituents exert smooth muscle relaxant and anti-spasmodic effects on the lower esophageal sphincter, stomach, duodenum, and large bowel. Moreover, peppermint oil can modulate visceral and central nervous system sensitivity. Taken together, these effects suggest using peppermint oil both for improved endoscopic performance and for treating functional dyspepsia and irritable bowel syndrome. Importantly, peppermint oil has an attractive safety profile compared to classical pharmacological treatments, especially in FGIDs. Peppermint oil is a safe herbal medicine therapy for application in gastroenterology, with promising scientific perspectives and rapidly expanding use in clinical practice.

Durable patient-reported outcomes following 60-day percutaneous peripheral nerve stimulation (PNS) of the medial branch nerves

BackgroundChronic low back pain (CLBP) is often associated with clinical evidence of central nervous system sensitization and finding a clear source of nociceptive input can be challenging. Conventional therapies targeting peripheral spinal pain structures can fail to address centrally-mediated, underlying causes of pain. Sixty-day percutaneous peripheral nerve stimulation (PNS) applied to the lumbar medial branch nerves is a non-surgical, non-opioid treatment that may restore the balance of peripheral inputs to the central nervous system and reverse maladaptive changes in central pain processing. As a minimally invasive, non-destructive treatment, percutaneous PNS was designed to be used earlier in the treatment continuum than radiofrequency ablation or permanently-implanted neurostimulation systems. ObjectiveThe objective of this clinical trial was to characterize the durability of responses to medial branch PNS in a prospective multicenter case series study of CLBP patients recalcitrant to multiple non-surgical treatments. DesignProspective, multicenter clinical trial. PopulationAdults with CLBP without radicular leg pain who had previously failed multiple types of conventional treatments. InterventionSixty-day percutaneous PNS applied to the lumbar medial branch nerves. MethodsPercutaneous PNS leads were implanted under image guidance (ultrasound and/or fluoroscopy) and treatment was applied for up to 60 days, after which the leads were removed. Participants were followed through 14 months (12 months after the 2-month PNS treatment). Prospectively-defined endpoints included assessments of pain intensity, disability, pain interference, health-related quality of life, depression, and patient global impression of change. ResultsTreatment of CLBP with 60-day percutaneous PNS treatment produced clinically meaningful improvements in average pain intensity, disability, and/or pain interference for a majority of participants through the entire 14 month follow up period without requiring permanent system implantation. The proportion of participants experiencing clinically meaningful improvement in at least one outcome (pain intensiy, disability, pain interference) with PNS was 91% after 2 months, 79% at 5 months, 73% at 8 months, 75% at 11 months, and 77% at 14 months. There were no serious or unanticipated study-related adverse events. ConclusionThis prospective multicenter clinical trial demonstrates the clinical utility of percutaneous PNS when applied to the medial branch nerves for the treatment of chronic low back pain recalcitrant to non-surgical treatments. Given the minimally invasive nature of percutaneous PNS and the significant benefits experienced by participants, percutaneous PNS provides a safe and effective first-line neuromodulation treatment for patients with CLBP that may obviate the need for neuroablative procedures or permanent neurostimulation system implantation.

Central sensitization in patients with deep endometriosis.

Dear Editor, The association between endometriosis and pelvic pain is widely known, but the specific mechanisms by which endometriosis causes pain are still poorly understood [1]. Central sensitization (CS) is a phenomenon in which alterations in the central nervous system cause changes in the perception of pain [2], and these changes have the potential to exacerbate pain symptoms and predispose women with endometriosis to the development of other chronic conditions. Previous research suggested that endometriosis-associated chronic pelvic pain is often related to the presence of CS [3] and could lead to worse response to treatments or lower health-related quality of life (HRQoL) and a higher risk of depression and anxiety. The Central Sensitization Inventory (CSI) was designed to apply the concept of CS to the clinical management of patients with chronic pain [4]. The CSI questionnaire has been validated to differentiate between centrally sensitized and non-sensitized patients in the chronic pain literature, having strong psychometric properties, good internal consistency, and good test–retest validity [4]. A recently published study has shown that CSI could serve as a tool to help identify patients with endometriosis who have pain contributors related to central nervous system sensitization [5]. On the other hand, previous studies evaluating patients with endometriosis did not take into account the severity and type of disease. Moreover, to our knowledge, no previous study has evaluated the presence of CS-related symptoms in patients with deep endometriosis (DE), the type of endometriosis associated with higher levels of pain [1].

Neurophysiology of pain education knowledge, pain disability, patient satisfaction and central sensitization in chronic musculoskeletal pain

Chronic musculoskeletal pains are multifaceted, and Central sensitization is a potential pathophysiological mechanism underlying a group of chronic musculoskeletal pain disorders. Neurophysiology of pain education knowledge and patient satisfaction levels of chronic musculoskeletal pain subjects may contribute to central nervous system sensitization. Hence, the aim of the study was to evaluate the impact of neurophysiology of pain education knowledge and patient satisfaction levels on central sensitization in large population of patient with chronic musculoskeletal pain. The study included 200 chronic musculoskeletal pain subjects that persisted more than 3 months with average age of 43.93±13.62. A cross-sectional study used non probability sampling. Neurophysiology of pain Questionnaire (NPQ) to know the conceptualization of pain, mood rating scale(MRS) to measure patient’s mood fluctuation because of pain, pain disability scale (PDS) for evaluating patients ability to perform certain activity, central sensitization inventory(CSI) to measure nervous system sensitization and patients satisfaction scale(PSS) to understand patient’s satisfaction towards the treatment and health care provider were used. Descriptive and correlation analyses were used for analysis. The correlation analyses showed that patient disability scale negatively correlated with mood scale and positively correlated with the age, duration of the condition, impact of pain on ADL and central sensitization. And there was a positive correlation between patient satisfaction and impact of pain on ADL. The age, mood, duration of the condition and pain disability were the factors behind central sensitization in patients with chronic musculoskeletal pain. And the neuro physiology of pain knowledge had impact on pain disability and patient satisfaction.

Bio Psychosocial Factors and Central Sensitization in Patients with Chronic Musculoskeletal Pain

Introduction: Central sensitization (CS) is a neurological sensitivity phenomenon that causes patients to perceive more pain and broader discomfort. However, the bio psychosocial factors associated with the phenomenon of perception continue to explore and further the current knowledge on CS in patients with chronic musculoskeletal pain. The main purpose of this study was to determine the extent of associative relationship between central nervous system sensitization and bio psychosocial measures in patients with chronic musculoskeletal pain. Settings and Design: An observational cross-sectional study was carried out in a tertiary care hospital’s outpatient unit. Methods and Materials: Two hundred patients with chronic musculoskeletal pain were included in the present cross-sectional study. They completed questionnaires such as Central sensitisation inventory (CSI), Tampa Scale of Kinesiophobia (TSK), Pain Catastrophizing index (PCI), Insomnia Severity Index (ISI), Widespread Pain Index (WPI), Symptom Severity Score (SS), Kessler Psychological Distress Scale (K10 SCORE) and Fatigue Severity Scale (FSS). Results: The bio psychosocial factors showed mild to moderate correlation with CSI score ,FSS (r=0.432); TSK (r=0.432); K10 score (r=0.450);PCI score (r=0.465); Total (WPI+SS) score (r=0.467) and ISI score(r=0.249).These bio psychosocial factors in a statistically significant hierarchical regression model showed 37.9 % variance on CSI score (F- 31.39;P&lt; 0.001) where kinesiophobia and Insomnia did not satisfy the model fit. Conclusion: Even the CS showed a significant association with bio psychosocial factors, it kept kinesiophobia and Insomnia out in its variance contribution.

Relationships of autonomic dysfunction with disease severity and neuropathic pain features in fibromyalgia: is it really a sympathetically maintained neuropathic pain?

BackgroundThe pathophysiology of fibromyalgia (FM) involves many mechanisms including central nervous system sensitization theory, autonomic nervous system (ANS) dysfunction, and recently small fiber neuropathy. While the small fiber neuropathy itself can cause ANS dysfunction and neuropathic pain (NP), it is still unknown whether ANS problems have an association with severity of disease and NP in patients with FM. The aim of this study was to evaluate ANS dysfunction in FM patients and to explore possible associations of ANS dysfunction with disease severity and NP.MethodsTwenty-nine FM patients and 20 healthy controls were included in this cross-sectional study. Participants were tested using sympathetic skin responses (SSR) and R-R interval variation analyses for sympathetic and parasympathetic ANS dysfunction, respectively. Disease severity and somatic symptoms of patients with FM were evaluated using the ACR-2010 scales and Fibromyalgia Impact Questionnaire, and NP symptoms were evaluated using the Pain Detect Questionnaire and Douleur Neuropathique questionnaire.ResultsFM patients were found to have ANS dysfunction characterized by increased sympathetic response and decreased parasympathetic response. SSR amplitudes were found to be correlated with a more severe disease. Although non-significant, NP severity tended to be associated with a decrease in sympathetic and parasympathetic activities.ConclusionsANS dysfunction may play a role in the pathophysiology of FM. The trend of decreased ANS functions in FM patients exhibiting NP contradicts the notion that FM is a sympathetically maintained NP and may be explained with small fiber involvement.