Pain Conditions Research Articles

Do we want to know the enormity of women's severe menstrual disorders and chronic pelvic pain?

ObjectiveThe purpose of this paper is to call for a nationwide study to assess the prevalence and incidence of women health problems related to menstrual disorders and severe pelvic pain. RationaleThe exact prevalence and incidence of endometriosis, adenomyosis, severe painful menstrual disorders, and of severe chronic pelvic pain are unknown. These issues severely impact women's quality of life and represent huge costs for our societies. Using adapted questionnaires, recent progresses in diagnosis and increased fundings announced by politicians, we can and should change this situation by performing a nationwide study to assess prevalence and incidence of these women problems in the French general population. The huge, anticipated costs of this study do appear quite reasonable when accounting for the enormous costs and societal consequences of endometriosis, menstrual disorders and severe pelvic pain. ConclusionThese long-awaited data will improve our understanding of the causes, consequences, and natural history of endometriosis. These data will allow women to better understand that pain is not always related to endometriosis, thus preventing unjustified fears. Physicians will be able to adapt and improve medical managements, particularly the diagnosis. Politicians will have the tools to improve women's health and gender equality.

Evaluating the Potential of Green Light Exposure on Nociception-A Mini Review.

The capacity of animals to react to unpleasant stimuli that might endanger their integrity is known as nociception. Pharmacological treatments do not show satisfactory results in response to nociception. In the recent era, light therapy emerged as a potential non-pharmacological approach for treating various diseases, including seasonal affective disorders, migraine, pain, and others. Evaluating the potential of green light exposure on nociception involves studying its effects on different types of pain and pain-related conditions and determining the optimal exposure methods. This review provides the beneficial effects of green light on the reduction in the frequency of pain. The green light exposure on nociception changes the activity of pain-related genes and proteins in cells. This review could provide insights into the underlying mechanisms by which green light modulates pain. Overall, evaluating the potential of green light exposure on nociception requires a multidisciplinary approach and should consider the safety, efficacy, optimal dose, and duration of green light exposure and the type of pain. However, few studies have been reported so far; therefore, light therapy for treating migraines require more studies on animal models to provide precise results of light effects on nociception.

Hippocampus diffusivity abnormalities in classical trigeminal neuralgia

Abstract Introduction: Patients with chronic pain frequently report cognitive symptoms that affect memory and attention, which are functions attributed to the hippocampus. Trigeminal neuralgia (TN) is a chronic neuropathic pain disorder characterized by paroxysmal attacks of unilateral orofacial pain. Given the stereotypical nature of TN pain and lack of negative symptoms including sensory loss, TN provides a unique model to investigate the hippocampal implications of chronic pain. Recent evidence demonstrated that TN is associated with macrostructural hippocampal abnormalities indicated by reduced subfield volumes; however, there is a paucity in our understanding of hippocampal microstructural abnormalities associated with TN. Objectives: To explore diffusivity metrics within the hippocampus, along with its functional and structural subfields, in patients with TN. Methods: To examine hippocampal microstructure, we utilized diffusion tensor imaging in 31 patients with TN and 21 controls. T1-weighted magnetic resonance images were segmented into hippocampal subfields and registered into diffusion-weighted imaging space. Fractional anisotropy (FA) and mean diffusivity were extracted for hippocampal subfields and longitudinal axis segmentations. Results: Patients with TN demonstrated reduced FA in bilateral whole hippocampi and hippocampal body and contralateral subregions CA2/3 and CA4, indicating microstructural hippocampal abnormalities. Notably, patients with TN showed significant correlation between age and hippocampal FA, while controls did not exhibit this correlation. These effects were driven chiefly by female patients with TN. Conclusion: This study demonstrates that TN is associated with microstructural hippocampal abnormalities, which may precede and potentially be temporally linked to volumetric hippocampal alterations demonstrated previously. These findings provide further evidence for the role of the hippocampus in chronic pain and suggest the potential for targeted interventions to mitigate cognitive symptoms in patients with chronic pain.

Prevalence and Risk Factors of Distal Symmetric Polyneuropathy Among Predominantly Non-Hispanic Black, Low-Income Patients.

Distal symmetric polyneuropathy (DSP) is a disabling, often painful condition associated with falls and reduced quality of life. Non-Hispanic Black people and people with low income are underrepresented in existing DSP studies; therefore, it is unknown whether data accurately reflect the prevalence, risk factors, and burden of disease in these populations. Patients older than 40 years presenting to an outpatient internal medicine clinic predominantly serving Medicaid patients in Flint, Michigan, were enrolled in a cross-sectional study. Demographics, clinical characteristics, including medication use, anthropomorphic measurements, fasting lipids, and hemoglobin A1c were collected. DSP was defined using the modified Toronto Clinical Neuropathy Score (mTCNS). Multivariable logistic regression was performed to model DSP and undiagnosed DSP as a function of potential risk factors age, metabolic syndrome, and race. DSP burden was measured using Peripheral Neuropathy Quality of Life Instrument-97. Two hundred participants were enrolled, and 169 (85%) completed all data collection. The population was 55% female of mean age (SD) 58.2 years (10.4) and 69% non-Hispanic Black. Among the population, 50% had diabetes, 67% had metabolic syndrome, and 47% had a household income <$20,000. DSP was present in 73% of the population, of which 75% were previously undiagnosed. Neuropathic pain was documented in 57% of participants with DSP. DSP based on mTCNS criteria was associated with older age (odds ratio [OR] 1.1 [95% confidence interval (CI) 1.03-1.2]) and metabolic syndrome (OR 4.4 [1.1-18.1]). Non-Hispanic Black participants had lower odds of DSP (OR 0.1 [0.01-0.4]) than non-Hispanic White and Hispanic participants. DSP burden was high, including increased pain, health-related worry, and poorer quality of life (all p < 0.001). DSP is extremely common and often underrecognized in this predominantly non-Hispanic Black, low-income population and leads to substantial disease burden. Metabolic syndrome is a highly prevalent, modifiable risk factor in this population that should be managed to lower DSP prevalence.

Substance P’s Impact on Chronic Pain and Psychiatric Conditions—A Narrative Review

Substance P (SP) plays a crucial role in pain modulation, with significant implications for major depressive disorder (MDD), anxiety disorders, and post-traumatic stress disorder (PTSD). Elevated SP levels are linked to heightened pain sensitivity and various psychiatric conditions, spurring interest in potential therapeutic interventions. In chronic pain, commonly associated with MDD and anxiety disorders, SP emerges as a key mediator in pain and emotional regulation. This review examines SP’s impact on pain perception and its contributions to MDD, anxiety disorders, and PTSD. The association of SP with increased pain sensitivity and chronic pain conditions underscores its importance in pain modulation. Additionally, SP influences the pathophysiology of MDD, anxiety disorders, and PTSD, highlighting its potential as a therapeutic target. Understanding SP’s diverse effects provides valuable insights into the mechanisms underlying these psychiatric disorders and their treatment. Further research is essential to explore SP modulation in psychiatric disorders and develop more effective treatment strategies.

Discovery of ITI-333, a Novel Orally Bioavailable Molecule Targeting Multiple Receptors for the Treatment of Pain and Other Disorders.

Development of more efficacious medications with improved safety profiles to manage and treat multiple forms of pain is a critical element of healthcare. To this end, we have designed and synthesized a novel class of tetracyclic pyridopyrroloquinoxalinone derivatives with analgesic properties. The receptor binding profiles and analgesic properties of these tetracyclic compounds were studied. Systematic optimizations of this novel scaffold culminated in the discovery of the clinical candidate, (6bR,10aS)-8-[3-(4-fluorophenoxy)propyl]-6b,7,8,9,10,10a-hexahydro-1H-pyrido[3',4':4,5]pyrrolo[1,2,3-de]quinoxalin-2(3H)-one (compound 5, ITI-333), which exhibited potent binding affinity to serotonin 5-HT2A (Ki = 8.3 nM) and μ-opioid receptors (MOR, Ki = 11 nM) and moderate affinity to adrenergic α1A (Ki = 28 nM) and dopamine D1 (Ki = 50 nM) receptors. ITI-333 acts as a 5-HT2A receptor antagonist, a MOR partial agonist, and an adrenergic α1A receptor antagonist. ITI-333 exhibited dose-dependent analgesic effects in rodent models of acute pain. Currently, this investigational new drug is in phase I clinical development.

Medical cannabis use in Australia seven years after legalisation: findings from the online Cannabis as Medicine Survey 2022–2023 (CAMS-22)

BackgroundCannabis was legalised for medical purposes in 2016. Uptake was initially slow, but since 2019 there has been a large increase in the number of Australians who have been prescribed cannabis for medical reasons. Yet a significant number of consumers continue to treat their medical conditions via illicitly-sourced cannabis. Little is known about how these two groups of medical cannabis consumers differ.MethodsThe anonymous Cannabis-As-Medicine Survey 2022–2023 (CAMS-22) was available for completion online from December 2022 to April 2023 to adult Australians who had used cannabis to treat a medical condition in the previous year. Recruitment occurred through social media, consumer forums, and medical practices. Questions included demographic characteristics, patterns of cannabis use, conditions treated, and self-rated effectiveness.ResultsOf the 3323 respondents included in these analyses, 2352 (73%) mainly used prescribed medical cannabis, 871 (27%) mainly used illicit. Prescribed users were significantly more likely than illicit users to have had their health condition diagnosed (OR = 1.7, 95% CI 1.3, 2.2), to consume their cannabis via oral (OR = 1.9; CI 1.5, 2.4) or vaporised (OR = 5.2; CI 4.0, 6.8) routes, and to be sure of the composition of their medical cannabis (OR = 25.0; CI 16.7, 50.0). Prescribed users were significantly less likely to have used cannabis non-medically before medical use (OR = 0.6, CI 0.5, 0.7), consume cannabis via smoked routes (OR = 0.2, CI 0.1, 0.2), and to report any side effects (OR = 0.1; CI 0.1, 0.2). The most common conditions among both prescribed and illicit users were pain (37%), mental health (36%), and sleep (15%) conditions. Prescribed users were significantly more likely to use cannabis to mainly treat a pain (OR = 1.3; CI 1.1, 1.5) or sleep condition (OR = 1.4; CI 1.1, 1.7) and less likely to treat a mental health condition (OR = 0.8; CI 0.7, 0.9). There were no between-group differences in effectiveness with 97% saying medical cannabis had improved their symptoms.ConclusionsFrom a harm-reduction perspective there is much to recommend prescribed medical cannabis; it has fewer side-effects than illicit, is used more safely (oral or vaporised versus smoked routes), gives consumers greater certainty regarding the composition and quality of their medicine, and does not risk exposure to the criminal justice system. Of concern, however, is the apparent willingness of prescribers to prescribe for indications for which there is limited evidence of efficacy, such as mental health and sleep conditions.

The Use of Compounds Derived from Cannabis sativa in the Treatment of Epilepsy, Painful Conditions, and Neuropsychiatric and Neurodegenerative Disorders

The Use of Compounds Derived from Cannabis sativa in the Treatment of Epilepsy, Painful Conditions, and Neuropsychiatric and Neurodegenerative Disorders

Effects of mind-regulating acupuncture on pain, negative emotion and sleep quality in patients with postherpetic neuralgia： a randomized controlled pilot trial.

To observe the effect of mind-regulating acupuncture on pain intensity, sleep quality, negative emotion in patients with postherpetic neuralgia (PHN), and evaluate the clinical effect of mind-regulating acupuncture combined with surrounding needling and heavy moxibustion at Ashi points (Extra) in treatment of PHN. The patients with PHN were randomly divided into a control group (35 cases, 2 cases dropped out) and a comprehensive therapy group (35 cases). The patients in the control group were treated with surrounding needling and heavy moxibustion at Ashi points. In the comprehensive therapy group, the mind-regulating acupuncture therapy was delivered besides the treatment as the control group. The treatment was given once daily, one course of treatment was composed of 6 days and 2 courses were required in the 2 groups. Before and after treatment, the pain conditions were assessed using pain rating index (PRI), visual analogue scale (VAS) and present pain intensity (PPI), the negative emotions were assessed using Hamilton anxiety scale (HAMA) and Hamilton depression scale (HAMD), and the sleep quality with Pittsburgh sleep quality index (PSQI). One week before and one week after treatment, the average sleep time was recorded. The therapeutic effect of 2 groups was evaluated. The effective cases of 2 groups were followed up in 2 months after treatment completion and the recurrence of neuralgia was recorded. There were no statistical differences in the above indicators between the 2 groups before treatment. After 2 courses of treatment, the scores of PRI, VAS, PPI, HAMA, HAMD and PSQI were reduced when compared with those before treatment in the patients of the 2 groups (P<0.05), and the average sleep time was increased (P<0.05). The scores of PRI, VAS, PPI, HAMA, HAMD and PSQI in the comprehensive therapy group, as well as the average sleep time were all improved when compared with those of the control group (P<0.05). The total effective rate in the comprehensive therapy group (34/35, 97.14%) was higher than that of the control group (27/33, 81.82%, P<0.05) and the recurrence rate was lower (［2/34, 5.88%］vs［8/27, 29.63%］, P<0.05). The combination of mind-regulating acupuncture with surrounding needling and heavy moxibustion at Ashi acupoint can effectively relieve PHN. Compared with the traditional surrounding acupuncture in pain area combined with moxibustion at Ashi points, this comprehensive therapy is more effective for ameliorating pain intensity, improving sleep quality and reducing negative emotions. It is also effective for declining the recurrence.

Assessment for Diabetic Neuropathy: Treatment and Neurobiological Perspective.

Diabetic neuropathy, also known as diabetic peripheral sensorimotor neuropathy (DPN), is a consequential complexity of diabetes, alongside diabetic nephropathy, diabetic cardiomyopathy, and diabetic retinopathy. It is characterized by signs and symptoms of peripheral nerve damage in diabetes patients after ruling out other causes. Approximately 20% of people with diabetes are affected by this painful and severe condition. The development of diabetic neuropathy is influenced by factors such as impaired blood flow to the peripheral nerves and metabolic issues, including increased polyol pathway activation, myo-inositol loss, and nonenzymatic glycation. The present review article provides a brief overview of the pathological changes in diabetic neuropathy and the mechanisms and types of DPN. Various diagnostic tests and biomarkers are available to assess nerve damage and its severity. Pharmacotherapy for neuropathic pain in diabetic neuropathy is complex. This review will explore current treatment options and potential future developments to improve the quality of life for patients suffering from diabetic neuropathy.

Magic Realism in Rabindra Sameer's Mrityuko Aayu

This article analyzes the novel Mrityuko Aayu in the light of Magic Realism. Applying magic realism is methodological approach for critical analysis of the novel in this article. It follows interpretive textual analysis. Free translation has been used while taking the citation from the novel. I have drawn the conclusion that the novel is a magic realist novel as it has introduced innovative style of narrating the story. The story begins from the death of the protagonist, but he is capable of seeing everything even after the death. It has blended mundane and supernatural, ordinary and extraordinary and real and fantastical elements in an unquestionable way. The novel's extracts are analyzed within five parameters that include fantastical elements, real world setting, incorporation of myth, meta-fiction and social/ political critique. Even after the death of the protagonist, the story moves ahead from the spirit's perspective. The spirit is capable of seeing, feeling and experiencing everything. The readers accept all such actions and happenings as normal without questioning the reliability of them and feel sorry for his painful and pathetic condition. Therefore, the writer is successful in using magic realism in the novel. It is hoped that this article will encourage researchers to study other works of fiction from the point of view of Magic Realism.

Global trends and hotspots in pain associated with bipolar disorder in the last 20 years: a bibliometric analysis

PurposeThe prevalence of comorbid pain and Bipolar Disorder in clinical practice continues to be high, with an increasing number of related publications. However, no study has used bibliometric methods to analyze the research progress and knowledge structure in this field. Our research is dedicated to systematically exploring the global trends and focal points in scientific research on pain comorbidity with bipolar disorder from 2003 to 2023, with the goal of contributing to the field.MethodsRelevant publications in this field were retrieved from the Web of Science core collection database (WOSSCC). And we used VOSviewer, CiteSpace, and the R package “Bibliometrix” for bibliometric analysis.ResultsA total of 485 publications (including 360 articles and 125 reviews) from 66 countries, 1019 institutions, were included in this study. Univ Toront and Kings Coll London are the leading research institutions in this field. J Affect Disorders contributed the largest number of articles, and is the most co-cited journal. Of the 2,537 scholars who participated in the study, Stubbs B, Vancampfort D, and Abdin E had the largest number of articles. Stubbs B is the most co-cited author. “chronic pain,” “neuropathic pain,” “psychological pain” are the keywords in the research.ConclusionThis is the first bibliometric analysis of pain-related bipolar disorder. There is growing interest in the area of pain and comorbid bipolar disorder. Focusing on different types of pain in bipolar disorder and emphasizing pain management in bipolar disorder are research hotspots and future trends. The study of pain related bipolar disorder still has significant potential for development, and we look forward to more high-quality research in the future.

Co-occurring Chronic Pain and PTSD Among US Military Veterans: Prevalence, Correlates, and Functioning.

The prevalence of co-occurring chronic pain and posttraumatic stress disorder (PTSD) has yet to be established in a nationally representative sample of US veterans, and little is known about the individual contributing roles of these disorders to the psychiatric and functional burden of this comorbidity. To determine the prevalence of chronic pain, PTSD, and co-occurring chronic pain and PTSD, and psychiatric comorbidities and psychosocial functioning in these groups. Data were analyzed from the National Health and Resilience in Veterans Study, which surveyed a nationally representative sample of US veterans. Veterans (n=4069) were classified into four groups: control (i.e., no PTSD or chronic pain), chronic pain only, PTSD only, and co-occurring chronic pain and PTSD. A probable PTSD diagnosis was established using the PTSD Checklist for DSM-5, and a chronic pain diagnosis using a self-report item that queried health care professional diagnoses. Psychiatric and functional status were assessed using the Patient Health Questionnaire-4, Alcohol Use Disorders Identification Test, Screen of Drug Use, Suicide Behaviors Questionnaire-Revised, Short Form Health Survey-8, Brief Inventory of Psychosocial Functioning, and Medical Outcomes Study Cognitive Functioning Scale. A total of 3.8% of veterans reported both probable PTSD and a diagnosis of chronic pain. Relative to veterans with chronic pain alone, those with co-occurring chronic pain and probable PTSD were more likely to screen positive for psychiatric disorders (odds ratios [ORs]=2.59-9.88) and scored lower on measures of psychosocial functioning (Cohen's ds=0.38-1.43). Relative to veterans with probable PTSD only, those with co-occurring chronic pain and probable PTSD were more likely to have attempted suicide (OR=4.79; 95%CI, 1.81-12.69). Results underscore the importance of whole health care that considers a broad range of health and functional domains in the assessment and treatment of co-occurring chronic pain and PTSD in veterans.

Onychocryptosis Is Associated with Low Income in a Matched Cohort Study Using the All of Us Database

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Onychocryptosis is a common and often painful nail condition, but risk factors have been relatively unexplored. We aimed to analyze associations between onychocryptosis, comorbidities, and income level. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Using the National Institute of Health All of Us Research Program Database, a matched case-control study was performed for patients with onychocryptosis diagnosis and comorbidities and lifestyle factors. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; A total of 6,246 cases of onychocryptosis and 24,984 controls were analyzed. Patients with onychocryptosis versus controls had increased risk of onychogryphosis (OR 5.66; 95% CI 4.87, 6.58), onychomycosis (2.63; 2.06, 3.36), hallux valgus (1.68; 1.50, 1.87), type 2 diabetes mellitus (1.49; 1.40, 1.60), obesity (1.38; 1.30, 1.48), and peripheral vascular disease (1.24; 1.14, 1.35) compared to controls. Patients who reported living in low-income households more often had onychocryptosis (reference group annual income &amp;gt;200 k; annual income &amp;lt;10 k USD, OR: 1.76; 95% CI: 1.46, 2.12, &lt;i&gt;p&lt;/i&gt; &amp;lt; 0.001 vs. annual income 150–200 k USD, OR: 1.26; 95% CI: 0.99, 1.61, &lt;i&gt;p&lt;/i&gt; = 0.06). &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; Low income, obesity, PVD, and T2DM were associated with onychocryptosis diagnosis. It is recommended that these at-risk populations be screened for onychocryptosis and counseled on proper nail trimming techniques. Future studies are needed to examine the relationship between household income and onychocryptosis risk.

Nabilone for Chronic Non-Cancer Pain

What Is the Issue? Chronic pain is pain that lasts beyond 3 months. Chronic non-cancer pain conditions include osteoarthritis, low back pain, musculoskeletal pain, fibromyalgia, and neuropathic pain. Approximately 1 in 5 people in Canada live with chronic pain. Nabilone (a cannabinoid) is indicated for the management of severe nausea and vomiting associated with cancer chemotherapy. Nabilone is also used in the management of chronic non-cancer pain. It is important to understand the potential benefits and harms of nabilone in people living with chronic non-cancer pain to support decision-making. What Did We Do? We sought to identify, summarize, and critically appraise literature comparing the clinical effectiveness of nabilone and placebo or alternative pharmacological options. We also searched for evidence-based guidelines that provide recommendations about the use of nabilone for the treatment of chronic non-cancer pain. We searched key resources, including journal citation databases, and conducted a focused internet search for relevant evidence published since 2015. One reviewer screened articles for inclusion based on predefined criteria, critically appraised the included studies, and narratively summarized the findings. What Did We Find? We found 1 overview of reviews and 2 systematic reviews that assessed the clinical efficacy and safety of nabilone for the treatment of chronic non-cancer pain. The evidence on the clinical efficacy of nabilone was mixed with some studies reporting an improvement in pain in those treated with nabilone versus placebo or active comparators and other studies reporting no difference between groups. Adverse events were more common in people living with chronic non-cancer pain who received nabilone than those who received placebo, ibuprofen, or amitriptyline. Adverse events were more common in those who received dihydrocodeine or gabapentin than nabilone. It is uncertain if nabilone is an effective treatment for people living with chronic non-cancer pain due to the varied results and methodological limitations of the included studies. We found 1 guideline that included a recommendation specific to nabilone and 2 guidelines that included recommendations on the use of cannabinoids in general. One guideline recommends against the use of nabilone for chronic pain, 1 guideline recommends offering a trial of non-inhaled cannabinoids (such as nabilone) for people living with chronic pain, and 1 guideline suggests cannabinoids be avoided in people with osteoarthritis and low back pain and discussed with people with neuropathic pain. What Does This Mean? Due to the uncertainty of the clinical evidence, decision-makers may wish to consider other factors such as costs, equity, and patient values and preferences when making decisions on the use of nabilone for people living with chronic non-cancer pain. Future high-quality, longer-term (e.g., RCT with follow-up studies) studies are needed to understand the efficacy and safety of nabilone for the treatment of people living with chronic non-cancer pain.

Isolated Kratom Use Disorder Treated with Extended-Release Buprenorphine Taper.

This case report highlights a 36-year-old male without history of psychiatric disease, chronic pain, or substance use disorder who developed severe substance use disorder per Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria to kratom. He was successfully treated with sublingual buprenorphine after a 3-year period of intermittent withdrawal management and trials of oral and extended-release injectable naltrexone. After a period of abstinence from kratom, he was tapered from buprenorphine using 2 monthly injections of 100 mg extended-release buprenorphine. His case underscores some of the current uncertainties around kratom use disorder diagnosis and treatment.

Prevention of persistent pain with lidocaine infusions in breast cancer surgery (PLAN): study protocol for a multicenter randomized controlled trial

BackgroundPersistent pain is a common yet debilitating complication after breast cancer surgery. Given the pervasive effects of this pain disorder on the patient and healthcare system, post-mastectomy pain syndrome (PMPS) is becoming a larger population health problem, especially as the prognosis and survivorship of breast cancer increases. Interventions that prevent persistent pain after breast surgery are needed to improve the quality of life of breast cancer survivors. An intraoperative intravenous lidocaine infusion has emerged as a potential intervention to decrease the incidence of PMPS. We aim to determine the definitive effects of this intervention in patients undergoing breast cancer surgery.MethodsPLAN will be a multicenter, parallel-group, blinded, 1:1 randomized, placebo-controlled trial of 1,602 patients undergoing breast cancer surgery. Adult patients scheduled for a lumpectomy or mastectomy will be randomized to receive an intravenous 2% lidocaine bolus of 1.5 mg/kg with induction of anesthesia, followed by a 2.0 mg/kg/h infusion until the end of surgery, or placebo solution (normal saline) at the same volume. The primary outcome will be the incidence of persistent pain at 3 months. Secondary outcomes include the incidence of pain and opioid consumption at 1 h, 1–3 days, and 12 months after surgery, as well as emotional, physical, and functional parameters, and cost-effectiveness.DiscussionThis trial aims to provide definitive evidence on an intervention that could potentially prevent persistent pain after breast cancer surgery. If this trial is successful, lidocaine infusion would be integrated as standard of care in breast cancer management. This inexpensive, widely available, and easily administered intervention has the potential to reduce pain and suffering in an already afflicted patient population, decrease the substantial costs of chronic pain management, potentially decrease opioid use, and improve the quality of life in patients.Trial registrationThis trial has been registered on clinicaltrials.gov (NCT04874038, Dr. James Khan. Date of registration: May 5, 2021).

Dilip's Transmucosal Internal Sphincterotomy: A Simplified Approach to Lateral Internal Sphincterotomy for Fissure-in-Ano.

Fissure in ano is a prevalent and painful condition, typically treated by lateral internal sphincterotomy (LIS) after conservative measures fail. Dilip's transmucosal internal sphincterotomy (TMIS) introduces a simplified approach that reduces the risk of damaging the external sphincter, making it particularly suitable for less experienced surgeons. This innovation offers a less invasive method with minimal risk of incontinence, providing a safer, more accessible option. TMIS simplifies the LIS process, offering a tailored approach that eliminates the need for extensive dissection. This method allows surgeons complete control over the internal sphincter bundle, facilitating a precise, customizable cut without the risks associated with traditional LIS, especially in obese patients where the intersphincteric groove is not visible, leading to potentially harmful blind incisions. The procedure is performed under saddle block anesthesia with the patient in lithotomy position. A distinctive approach involving the use of retractors and stay sutures allows the internal sphincter to be made prominent and secured without extensive dissection. The division of the internal sphincter is achieved through a minimal mucosal incision, requiring no closure and significantly reducing postoperative pain and complications. Between December 2020 and February 2022, 124 patients received TMIS, showing significant benefits with a median operative time of 7 minutes and low post-operative pain. With a 2.5% infection rate effectively managed and a 3% transient incontinence rate, the majority healed within 9 weeks. Recurrence was rare at 1.6%. TMIS presents significant advantages over traditional LIS, including reduced pain, lower risk of complications such as hematoma, abscess, or fistula formation, and the absence of painful postoperative nodules. TMIS's success suggests it should be incorporated into surgical education, offering a less daunting, more reproducible method for treating fissure-in-ano, especially beneficial for junior surgeons and improving patient outcomes.

Schwann cell TRPA1 elicits reserpine-induced fibromyalgia pain in mice.

Fibromyalgia is a complex clinical disorder with an unknown aetiology, characterized by generalized pain and co-morbid symptoms such as anxiety and depression. An imbalance of oxidants and antioxidants is proposed to play a pivotal role in the pathogenesis of fibromyalgia symptoms. However, the precise mechanisms by which oxidative stress contributes to fibromyalgia-induced pain remain unclear. The transient receptor potential ankyrin 1 (TRPA1) channel, known as both a pain sensor and an oxidative stress sensor, has been implicated in various painful conditions. The feed-forward mechanism that implicates reactive oxygen species (ROS) driven by TRPA1 was investigated in a reserpine-induced fibromyalgia model in C57BL/6J mice employing pharmacological interventions and genetic approaches. Reserpine-treated mice developed pain-like behaviours (mechanical/cold hypersensitivity) and early anxiety-depressive-like disorders, accompanied by increased levels of oxidative stress markers in the sciatic nerve tissues. These effects were not observed upon pharmacological blockade or global genetic deletion of the TRPA1 channel and macrophage depletion. Furthermore, we demonstrated that selective silencing of TRPA1 in Schwann cells reduced reserpine-induced neuroinflammation (NADPH oxidase 1-dependent ROS generation and macrophage increase in the sciatic nerve) and attenuated fibromyalgia-like behaviours. Activated Schwann cells expressing TRPA1 promote an intracellular pathway culminating in the release of ROS and recruitment of macrophages in the mouse sciatic nerve. These cellular and molecular events sustain mechanical and cold hypersensitivity in the reserpine-evoked fibromyalgia model. Targeting TRPA1 channels on Schwann cells could offer a novel therapeutic approach for managing fibromyalgia-related behaviours.

Cytokines in Bladder Pain Syndrome: A Review of the Literature.

Bladder pain syndrome (BPS) is poorly understood with both the aetiology and pathophysiology being unknown. Symptoms overlap with other disorders, such as overactive bladder (OAB) and chronic pelvic pain disorders such as endometriosis, making a consensus on how to diagnosis and manage patients challenging. The development of biomarkers for BPS may be the key to understanding more about its pathophysiology, as well as aiding diagnosis, subclassification, and discovering new drug targets for its management. As inflammation is widely understood to hold a central role in BPS, the evaluation of cytokines has gained interest. This article summarises the current literature and understanding of urinary, serum, and bladder tissue cytokines found elevated in patients with bladder pain syndrome. literature search using Pub Med with the keywords "bladder pain syndrome", "painful bladder syndrome", "bladder pain", "Interstitial cystitis" AND "cytokines" or "inflammation". This study was except from institutional approval. Thirty-six cytokines have been identified as being statistically significantly elevated in either the serum, urine, or bladder tissue of patients with bladder pain syndrome in the 22 studies identified in this review of the literature. These cytokines include those from the interleukin group (n = 14), the CXC chemokine group (n = 5), and the C-C chemokine group (n = 7). CXCL-1, CXCL-8, CXCL-9, CXCL-10, CXCL-11 from the CXC chemokine group, and CCL2, CCL4, CCL5, CCL7, and CCL11 from the C-C chemokine group have been found to be significantly elevated in patients with bladder pain in the literature. Many of these analytes also have supporting evidence for their roles in bladder pain from animal models and studies in other chronic inflammatory conditions. It is likely that a single cytokine will not serve as an adequate biomarker of disease in bladder pain syndrome for either diagnosis or disease severity. Instead, panels of inflammatory mediators may reveal more about the different pathways of inflammation leading to similar presentations of bladder pain in patients.