Search Results (319)

Irritable bowel syndrome (IBS) is a gut–brain axis chronic disorder, characterized by recurrent abdominal pain and altered bowel habits in the absence of organic pathology. Nutrition plays a central role in symptom management, yet no single dietary strategy has demonstrated universal effectiveness. This narrative review critically evaluates current nutritional approaches to IBS. The low-Fermentable Oligo-, Di-, Mono-saccharides and Polyols (FODMAP) diet is the most extensively studied and provides short-term symptom relief, but its long-term effects on microbiota diversity remain concerning. The Mediterranean diet, due to its anti-inflammatory and prebiotic properties, offers a sustainable, microbiota-friendly option; however, it has specific limitations in the context of IBS, particularly due to the adverse effects of certain FODMAP-rich foods. A gluten-free diet may benefit individuals with suspected non-celiac gluten sensitivity, although improvements are often attributed to fructan restriction and placebo and nocebo effects. Lactose-free diets are effective in patients with documented lactose intolerance, while a high-soluble-fiber diet is beneficial for constipation-predominant IBS. IgG-based elimination diets are emerging but remain controversial and require further validation. In this review, we present the 10 dietary commandments for IBS, pragmatic and easily retained recommendations. It advocates a personalized, flexible, and multidisciplinary management approach, avoiding rigidity and standardized protocols, with the aim of optimizing adherence, symptom mitigation, and health-related quality of life. Future research should aim to evaluate, in real-world clinical settings, the impact and applicability of the 10 dietary commandments for IBS in terms of symptom improvement and quality of life Full article

Chronic visceral pain, a significant contributor to morbidity in the United States, affects millions and results in substantial economic costs. Despite its impact, the mechanisms underlying disorders of gut–brain interaction (DGBIs), such as irritable bowel syndrome (IBS), remain poorly understood. Visceral hypersensitivity, a hallmark of chronic visceral pain, involves an enhanced pain response in internal organs to normal stimuli. Various factors like inflammation, intestinal hyperpermeability, and epigenetic modifications influence its presentation. Emerging evidence suggests that persistent colonic stimuli, disrupted gut barriers, and altered non-coding RNA (ncRNA) expression contribute to the pathophysiology of visceral pain. Additionally, cross-sensitization of afferent pathways shared by pelvic organs underpins the overlap of chronic pelvic pain disorders, such as interstitial cystitis and IBS. Central sensitization and viscerosomatic convergence further exacerbate pain, with evidence showing IBS patients exhibit hypersensitivity to both visceral and somatic stimuli. The molecular mechanisms of visceral pain involve critical mediators such as cytokines, prostaglandins, and neuropeptides, alongside ion channels like transient receptor potential vanilloid 1 (TRPV1) and acid-sensing ion channels (ASICs). These molecular insights indicate potential therapeutic targets and highlight the possible use of TRPV1 antagonists and ASIC inhibitors to mitigate visceral pain. This review explores the neurophysiological pathways of visceral pain, focusing on peripheral and central sensitization mechanisms, to advance the development of targeted treatments for chronic pain syndromes, particularly IBS and related disorders. Full article

Neuropathic pain (NP) is a prevalent clinical condition resulting from diseases or injuries affecting the somatosensory system. Conventional analgesics often exhibit limited efficacy, leading to suboptimal therapeutic outcomes. The pathogenesis of NP is complex and involves multiple mechanisms. The existing evidence suggests that maladaptive neuronal plasticity plays a central role in NP development. Additionally, emerging research highlights the contribution of neuroinflammatory responses mediated by glial cells in the onset of NP and associated sensory hypersensitivity. Among non-invasive neuromodulation techniques, transcranial direct current stimulation (tDCS) has gained prominence as a potential treatment for NP. Numerous studies have demonstrated its analgesic effects; however, the precise regulatory mechanisms remain unclear. The current evidence indicates that tDCS may alleviate NP by enhancing glial–neuronal interactions, which suppress nociceptive signaling pathways and reduce pain sensitivity. The reciprocal modulation between tDCS-mediated anti-inflammatory actions, as evidenced by decreased levels of pro-inflammatory cytokines and increased levels of anti-inflammatory mediators, and its facilitation of adaptive neural plasticity represents a particularly compelling therapeutic axis. This review elucidates inflammatory regulation by tDCS as a fundamental mechanism for NP alleviation, while delineating important unresolved questions regarding these complex interactions. Full article

Chronic neck pain is a multifactorial condition involving physical, psychological, and neurological dimensions. This case report describes the clinical course of a 25-year-old female with chronic neck pain and recurrent headaches who underwent a 6-week integrative intervention consisting of manual therapy and pain neuroscience-based sensorimotor retraining, administered three times per week. Outcome measures included the Headache Impact Test-6 (HIT-6), Neck Pain and Disability Scale (NPDS), Pain Catastrophizing Scale (PCS), Fear-Avoidance Beliefs Questionnaire (FABQ), pressure pain threshold (PPT), cervical range of motion (CROM), and functional near-infrared spectroscopy (fNIRS) to assess brain activity. Following the intervention, the patient demonstrated marked reductions in pain and psychological distress: HIT-6 decreased from 63 to 24 (61.9%), NPDS from 31 to 4 (87.1%), FABQ from 24 to 0 (100%), and PCS from 19 to 2 (89.5%). Improvements in PPT and CROM were also observed. fNIRS revealed decreased dorsolateral prefrontal cortex (DLPFC) activation during pain stimulation and movement tasks, suggesting a possible reduction in central sensitization burden. These findings illustrate that an integrative approach targeting biopsychosocial pain mechanisms may be beneficial in managing chronic neck pain, improving function, and modulating cortical responses. This report provides preliminary evidence in support of the clinical relevance of combining manual therapy with neurocognitive retraining in similar patients. Full article

Background/Objectives: Painful diabetic peripheral neuropathy (pDPN) significantly impacts quality of life, yet its diagnosis remains challenging due to reliance on subjective pain reports and limited objective biomarkers. This meta-analysis evaluated corneal nerve morphology parameters; corneal nerve fibre length (CNFL), corneal nerve fibre density (CNFD), and corneal nerve branch density (CNBD), measured through in vivo confocal microscopy (IVCM), as potential tools for differentiating painful and painless forms of diabetic neuropathy. Methods: A systematic review was performed comparing corneal nerve morphology across four groups: painful diabetic neuropathy (pDPN), non-painful diabetic neuropathy (npDPN), diabetes without neuropathy (DPN-), and healthy controls. Literature search extended over MEDLINE, EMBASE, Web of Science, and Cochrane Library, focusing on studies published since 2000. Study quality was assessed using the Newcastle–Ottawa Scale, while evidence certainly followed GRADE guidelines. Random-effects meta-analyses calculated mean differences (MDs) with 95% confidence intervals (CIs) for CNFL, CNFD, and CNBD. Results: Seven observational studies comprising 803 participants (213 pDPN, 275 npDPN, 99 DPN-, and 216 controls) revealed no significant differences between pDPN and npDPN groups in CNFL (MD = 0.79, 95% CI −0.64 to 2.22), CNFD (MD = 1.67, 95% CI −0.14 to 3.47), or CNBD (MD = 1.84, 95% CI −4.31 to 7.98). However, all metrics were markedly reduced in pDPN compared to DPN- and healthy controls. Conclusions: While effective in identifying diabetic neuropathy, common corneal nerve morphology parameters cannot reliably distinguish pDPN from npDPN. This highlights the need for research into mechanisms like central sensitization, inflammation, and micro-neuromas, which could refine diagnostic and therapeutic approaches for pDPN. Full article

Opioid use in patients with sleep disordered breathing (SDB) presents therapeutic challenges within chronic pain and sleep medicine. Opioids impair respiratory drive through μ-opioid receptor activation in brainstem respiratory centers, exacerbating both obstructive and central apneas. Chronic opioid use is also linked to a high prevalence of central sleep apnea and increased nocturnal hypoventilation. Simultaneously, SDB contributes to heightened pain sensitivity via intermittent hypoxia, systemic inflammation, and alterations in neural plasticity. These mechanisms may influence opioid efficacy and dosing requirements. This review summarizes current evidence on how SDB and opioid use interact, emphasizing chronic opioid use in the setting of chronic pain management. We discuss the underlying mechanisms, clinical impacts, and potential avenues for enhanced diagnosis and therapy in this population. We conclude that the intersection of SDB and opioid use presents a complex clinical challenge that demands a multidisciplinary approach. Enhanced screening, personalized pharmacologic strategies, and integration of advanced diagnostics are essential for mitigating risks and optimizing care. Future research should focus on mechanistic studies and interventional trials to guide evidence-based management of this high-risk population. Full article

Objectives: This study aims to identify the effectiveness of exercise in chronic tension-type headache and chronic migraine. Methods: The PICOS (Population, Intervention, Comparator, Outcomes, Study design) strategy was followed, where P—patients with chronic tension-type headache or chronic migraine; I—exercise; C—conventional treatment; O—pain reduction; and S—RCTs (randomized controlled trials) and quasi-experimental trials. Studies with a high risk of bias according to the RoB 2 (Risk of Bias) scale and with a score < 6 according to the PEDro (Physiotherapy Evidence Database) scale were excluded. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement was followed. The databases Pubmed, Web of Science, and Scopus were searched in November 2024. The PEDro and RoB2 scales were used to assess the risk of bias and internal validity of the studies. The results were synthesized qualitatively. Results: Ten studies with a total sample of 848 subjects were analyzed, comparing therapeutic interventions with an exercise versus conventional treatment. In most of the studies, the exercise group significantly outperformed the control group in pain reduction. Discussion: The findings suggest that exercise improves central pain modulation and reinforces the potential of body strategies such as postural integration. The main limitations found were the limited evidence on exercise’s role in chronic tension-type headache or migraine and the risk of bias due to the difficulty of blinding patients, therapists, and evaluators. Conclusions: The studies analyzed have shown that exercise could be an effective strategy to support the management of chronic tension-type headache and migraine. Full article

Ketamine, originally developed as an anesthetic, is gaining increasing attention due to its multifaceted pharmacological properties. In addition to its use in anesthesia, ketamine exerts potent analgesic effects via N-methyl-D-aspartate (NMDA) receptor antagonism, modulating pain perception and reducing central sensitization, particularly in chronic and neuropathic pain conditions. Emerging evidence also supports ketamine’s potential in the treatment of substance use disorder, where it may disrupt maladaptive reward-related memories and promote neuroplasticity which facilitates behavioral change. Moreover, in recent years, S-ketamine has shown rapid and potent antidepressant effects, especially in treatment-resistant depression (TRD), probably due to increased glutamatergic signaling, synaptic plasticity and the release of neurotrophic factors. This heterogeneous therapeutic profile positions ketamine as a unique agent at the interface of anesthesia, pain management, addiction medicine and psychiatry, warranting further exploration into its mechanism and long-term effectiveness. Full article

Adenylyl cyclases (ACs) are key regulators of cyclic adenosine monophosphate (cAMP) signaling—a pathway critical for neuroregeneration, synaptic plasticity, and neuronal survival. In both the central and peripheral nervous systems, injury-induced activation of ACs promotes axonal outgrowth and functional recovery through the stimulation of protein kinase A (PKA), exchange proteins directly activated by cAMP (Epac), and cAMP-response element-binding protein (CREB). Among the various AC isoforms, calcium-sensitive AC1, AC8, and AC5, as well as bicarbonate-responsive soluble AC (sAC), have emerged as crucial mediators of neuroplasticity and axon regeneration. These isoforms coordinate diverse cellular responses—including gene transcription, cytoskeletal remodeling, and neurotransmitter release—to metabolic, synaptic, and injury-related signals. Dysregulation of AC activity has been implicated in the pathophysiology of neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis, as well as in chronic pain syndromes. Pharmacological modulation of cAMP levels through AC activation, phosphodiesterase (PDE) inhibition, or pituitary adenylyl cyclase-activating polypeptide (PACAP) receptor signaling has shown therapeutic promise in preclinical models by enhancing neurogenesis, remyelination, and synaptic repair. Conversely, targeted inhibition of specific AC isoforms, particularly AC1, has demonstrated efficacy in reducing maladaptive plasticity and neuropathic pain. This review highlights the diverse roles of ACs in neuronal function and injury response and discusses emerging strategies for their therapeutic targeting. Full article

Systemic autoimmune rheumatic diseases (SARDs), such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren’s syndrome (SS), are traditionally characterized by chronic inflammation and immune-mediated damage to joints and other tissues. However, many patients also experience symptoms such as widespread pain, persistent fatigue, cognitive dysfunction, and autonomic disturbances that cannot be attributed directly or entirely to peripheral inflammation or structural pathology. These conditions suggest the involvement of interactions between the nervous and immune systems, which probably include both peripheral and central components. This review summarizes the current knowledge of neurological and neuroimmune mechanisms that may contribute to these symptoms in SARDs. Glial cell activation and neuroinflammation within the central nervous system (CNS), small-fiber neuropathy (SFN) affecting peripheral nociceptive pathways, central pain sensitization, and autonomic nervous system dysfunction will be discussed. In addition, the role of molecular mediators, including cytokines, neuropeptides, and microRNAs, that could potentially modulate neuroimmune signaling will be highlighted. Integrating findings from pathology, immunology, and neuroscience, this review seeks to provide a useful framework for understanding neuroimmune dysregulation in SARDs. It also highlights the clinical relevance of these mechanisms and summarizes new directions for diagnosis and treatment. Full article

Osteoarthritis (OA) is now widely recognized not merely as a cartilage-centric disease but as a multifactorial disorder affecting the entire joint as an organ, including the articular cartilage, subchondral bone, synovium, ligaments, menisci, and the innervating neural elements. This review explores the complex pathophysiology of OA with a focus on the emerging mechanisms of pain and inflammation that extend beyond articular cartilage degradation. Joint inflammation driven by immune activation in response to cellular stress signals promotes the release of pro-inflammatory mediators and catabolic enzymes. Key signaling pathways such as NF-κB, MAPKs, and JAK/STAT amplify these responses, and pain is sustained through peripheral and central sensitization, contributing to exacerbating symptoms even in the absence of visible joint damage. This review also integrates molecular and cellular mechanisms to highlight innovative therapies aimed at modifying both the structural damage and neurosensory drivers of pain. These approaches offer the potential to not only alleviate symptoms but also alter disease progression, signaling a move toward personalized, mechanism-based treatments. Given the intricate interactions among joint tissues, immune activation, and sensory processing, a comprehensive strategy that targets both structural degeneration and neuroinflammation is essential for the future of OA management. Emphasizing the joint as an integrated organ, we advocate for translational research linking molecular pathology with clinically meaningful outcomes. Full article

Objectives: This article describes the neurobiology of psychological injuries—chronic pain, concussion/mild traumatic brain injury (MTBI), and fear/posttraumatic stress disorder (PTSD)—toward elucidating common mechanisms in central and peripheral sensitization that contribute to their onset, exacerbation, and maintenance. Central sensitization refers to central nervous system (CNS) and related processes, while peripheral sensitization is typically referred to as receptor field expansion. The three psychological injury diagnoses/conditions are accompanied by impairments in function after negligent events (such as motor vehicle accidents (MVAs)) that lead to tort court action. Methods: The conducted literature review involved an extensive scoping review of recent neurobiological literature on chronic pain, PTSD, and MTBI. The literature review sought biological markers that distinguish them. Results: For chronic pain, concussion/MTBI, and fear/PTSD, this article reviewed definitions and critical neurobiological research. The literature review did not find evidence of biological markers, but the role of sensitization emerged as important. Conclusions: Common therapeutic processes, such as focusing on sensitization, might be helpful for these conditions. As for causal mechanisms related to sensitization in the causality of psychological injuries, the major ones hypothesized relate to the biopsychosocial model, psychological control, and activation–inhibition coordination. Full article

Background: Chronic shoulder pain is a prevalent musculoskeletal disorder often associated with central sensitisation, which limits the effectiveness of conventional therapies. Transcranial direct current stimulation (tDCS) has emerged as a non-invasive neuromodulatory intervention to modulate cortical excitability and potentially improve pain and functional outcomes. Methods: This scoping review followed the Joanna Briggs Institute (JBI) framework and PRISMA-ScR guidelines. A systematic search was conducted across MEDLINE, CENTRAL, Scopus, PEDro, and Web of Science to identify studies evaluating the effects of tDCS on pain and function in adults with rotator cuff disorders, myofascial pain syndrome (MPS), or subacromial pain syndrome (SAPS). Data were extracted and synthesised qualitatively. Results: Four studies met the inclusion criteria. tDCS demonstrated variable efficacy: some trials reported no additional benefit when used alongside corticosteroid injections or sensorimotor training (e.g., SAPS and rotator cuff tendinopathy), while others showed enhanced pain reduction and functional gains, particularly in MPS. Targeting the dorsolateral prefrontal cortex (DLPFC) appeared more effective than stimulating the primary motor cortex (M1) in modulating pain. Functional improvements were generally observed, though not consistently superior to sham interventions. Conclusions: Preliminary evidence suggests that tDCS may represent a promising adjunctive treatment for chronic shoulder pain, particularly in MPS. However, due to the limited number of studies and heterogeneity in methods, conclusions should be interpreted with caution. However, heterogeneity in study protocols, stimulation targets, and patient populations limits conclusive recommendations. Standardised protocols and larger trials are needed to determine the optimal application of tDCS in clinical shoulder pain management. Full article

Herein, a simple and effective analytical method was developed to monitor etoricoxib concentrations in human urine samples. Etoricoxib is a nonsteroidal anti-inflammatory drug for pain and inflammation relief in conditions such as osteoarthritis and rheumatoid arthritis. To determine its concentration, fabric phase sorptive extraction (FPSE) was combined with high-performance liquid chromatography and diode array detection (HPLC-DAD). FPSE is a green sample preparation technique that utilizes sol–gel-coated fabric substrates as extraction devices, offering numerous benefits in bioanalysis. Initially, different materials were tested for their affinity towards etoricoxib. The most critical FPSE parameters (i.e., sample amount, stirring rate, and adsorption time) were optimized using a face-centered central composite design (FC-CCD), while the remaining ones were explored by means of the one-variable-at-a-time approach. Afterwards, the analytical method was validated in terms of its selectivity, linearity, sensitivity, accuracy, and precision, while the environmental sustainability and the practicality of the method were also examined. The limit of detection was 0.03 μg mL⁻¹, and the lower limit of quantification was 0.10 μg mL⁻¹. The relative standard deviation was less than 7.2% in all cases, showing good precision. The proposed approach was successfully used to monitor urinary etoricoxib concentrations in real samples obtained from a volunteer after oral drug administration. Full article

Background and Clinical Significance: Altered pain perception is a diagnostic challenge for patients with a history of trauma and substance use. Familial dysautonomia (Riley-Day syndrome) may further complicate the sensory profiles. Case Presentation: We describe a male in his late twenties, originally from Central America, with a history of severe childhood trauma and chronic cannabis use, who reported diminished pain perception despite multiple injuries. Despite the absence of nociceptive pain (nociceptive hypoesthesia), abnormal sensations, such as tingling and itching (paresthesia), and occasionally unpleasant burning sensations (dysesthesia) were common symptoms in this case. Diagnosis: Clinical suspicion of familial dysautonomia was raised based on altered pain perception and minor autonomic signs. However, no genetic testing or neurological evaluation was performed. Psychological assessment revealed high levels of neuroticism, depression, and maladaptive coping. The Central Sensitization Inventory (CSI) and the Symptom Severity Scale (SS) further supported the presence of psychological symptoms suggestive of possible central sensitization. Outcome: Functional improvement was observed after a reduction in substance use and implementation of self-directed physical and cognitive rehabilitation. No standardized follow-up or formal interventions were recorded. Conclusions: This case illustrates the complexity of pain modulation in trauma-affected individuals and emphasizes the need for an integrative, interdisciplinary evaluation of atypical pain presentations. Full article