Uncategorized

: This review aims to analyze the last years' experience of applying spinal cord stimulation (SCS) in complex regional pain syndrome (CRPS) patients with persistent or refractory chronic pain. : This is a narrative review which was executed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and was carried out through the following databases: PUBMED and Cochrane Library. Also, a search for trials in the metaRegister of controlled trials (www.clinicaltrials.gov) was performed. : SCS provides pain reduction and improves sensory, vasomotor and sudomotor symptoms. It can reduce opioid using, offering better life quality for the patients. : SCS found to be an excellent therapeutic alternative for patients with CRPS. It offers immediate pain relief and allows patients to regain functionality and have a better quality of life.

The primary motor cortex (M1) is involved in the control of voluntary movements and is extensively mapped in this capacity. Although the M1 is implicated in modulation of pain, the underlying circuitry and causal underpinnings remain elusive. We unexpectedly unraveled a connection from the M1 to the nucleus accumbens reward circuitry through a M1 layer 6-mediodorsal thalamus pathway, which specifically suppresses negative emotional valence and associated coping behaviors in neuropathic pain. By contrast, layer 5 M1 neurons connect with specific cell populations in zona incerta and periaqueductal gray to suppress sensory hypersensitivity without altering pain affect. Thus, the M1 employs distinct, layer-specific pathways to attune sensory and aversive-emotional components of neuropathic pain, which can be exploited for purposes of pain relief.

Visceral pain (VP) is a global problem with complex etiologies and limited therapeutic options. Guanylyl cyclase C (GUCY2C), an intestinal receptor producing cyclic GMP which regulates luminal fluid secretion, has emerged as a therapeutic target for VP. Indeed, FDA-approved GUCY2C agonists ameliorate VP in patients with chronic constipation syndromes, although analgesic mechanisms remain obscure. Here, we reveal that intestinal GUCY2C is selectively enriched in neuropod cells, a type of enteroendocrine cell that synapses with submucosal neurons in mice and humans. GUCY2CHigh neuropod cells associate with co-cultured dorsal root ganglia neurons and induce hyperexcitability, reducing the rheobase and increasing the resulting number of evoked action potentials. Conversely, the GUCY2C agonist linaclotide eliminated neuronal hyperexcitability produced by GUCY2C-sufficient, but not GUCY2C-deficient, neuropod cells, an effect independent of bulk epithelial cells or extracellular cGMP. Genetic elimination of intestinal GUCY2C amplified nociceptive signaling and VP that was comparable to chemically-induced VP but refractory to linaclotide. Importantly, eliminating GUCY2C selectively in neuropod cells also increased nociceptive signaling and VP that was refractory to linaclotide. In the context of loss of GUCY2C hormones in patients with VP, these observations suggest a specific role for neuropod GUCY2C signaling in the pathophysiology and treatment of these pain syndromes.

Diffuse peripheral neuropathy is a well-known complication of several conditions, whereas many patients have peripheral neuropathy of unknown etiology and pathophyisology. Increased knowledge of mechanisms may provide insight into enteric neuropathy with gastrointestinal dysmotility. The aim of the present systematic review was to identify mechanisms behind diffuse idiopathic peripheral neuropathies in humans. Searches were performed in PubMed, Embase, and Web of Science. Human original and review articles, written in English, describing mechanisms behind diffuse peripheral neuropathy verified by objective examinations were intended to be studied. Articles that described animal models, well-described hereditary diseases, drug-induced neuropathy, pain syndromes, malnutrition, and local neuropathy were excluded. In total, 4712 articles were identified. After scrutinizing titles and abstracts, 633 remained and were studied in full text. After the removal of articles not fulfilling inclusion or exclusion criteria, 52 were finally included in this review. The most frequently described neuropathy was diabetic neuropathy, with a wide range of mechanisms involving mitochondrial dysfunction such as oxidative stress and inflammation. Microvascular changes in diabetes and vasculitis lead to ischemia and secondary oxidative stress with inflammation. Structural changes in neurons and glial cells are observed, with abnormalities in different neurotrophic factors. Neuropathy induced by autoantibodies or immunological mechanisms is described in infectious and systemic inflammatory diseases. Several ion channels may be involved in painful neuropathy. No study identified why some patients mainly develop large fiber neuropathy and others small fiber neuropathy. Metabolic and immunological factors and channelopathy may be considered in diffuse idiopathic peripheral neuropathy.

Inflammatory bowel diseases (IBDs) are chronic, immune-mediated disorders that include Crohn's disease and ulcerative colitis. A pediatric onset of disease occurs in about 10% of all cases. Clinical presentation of IBD with rectal bleeding or perianal disease warrants direct referral for endoscopic evaluation. In the absence of red-flag symptoms, a combination of patient history and blood and fecal biomarkers can help to distinguish suspected IBD from other causes of abdominal pain or diarrhea. The therapeutic management of pediatric IBD has evolved by taking into account predictors of poor outcome, which justifies the upfront use of anti-tumor necrosis factor therapy for patients at high risk for complicated disease. In treating patients with IBD, biochemical or endoscopic remission, rather than clinical remission, is the therapeutic goal because intestinal inflammation often persists despite resolution of abdominal symptoms. Pediatric IBD comes with unique additional challenges, such as growth impairment, pubertal delay, the psychology of adolescence, and development of body image. Even after remission has been achieved, many patients with IBD continue to experience nonspecific symptoms like abdominal pain and fatigue. Transfer to adult care is a well-recognized risk for disease relapse, which highlights patient vulnerability and the need for a transition program that is continued by the adult-oriented IBD team. The general pediatrician is an invaluable link in integrating these challenges in the clinical care of patients with IBD and optimizing their outcomes. This state-of-the-art review aims to provide general pediatricians with an update on pediatric IBD to facilitate interactions with pediatric gastrointestinal specialists.

The pharmacological management of nonspecific chronic low back pain (NCLBP) aims to restore daily activities and improve the quality of life. No magic bullet exists for NCLBP; interventions to reduce pain and disability are available, but long-term results are unpredictable. Education in this regard needs to improve. This is often hard to accept for clinicians and patients, and provides a fertile soil to quacks, faith healers, and gurus to promote miraculous non-evidence-based solutions. The management of NCLBP is not well codified and extremely heterogeneous, and residual symptoms are common. Depending on the individual severity of NCLPB, pharmacological management may range from nonopioid to opioid analgesics. It is important to identify patients with generalized sensory hypersensitivity, who may benefit from a dedicated therapy. In this editorial, we provide an evidenced-based overview of the principles of pharmacological management of NCLPB.

Chronic musculoskeletal pain (CMP) is characterised by pain related to the muscles or the joints with a duration of three months or more and is associated with high symptomatic burden in patients in primary health care. CMP is commonly associated with impaired mental health, which may affect the rehabilitation process. The primary aim of this study was to compare symptoms of anxiety, depression, fatigue, and insomnia in patients in primary health care with and without CMP. The secondary aim was to assess difference in mental health symptoms related to number of pain sites and pain intensity.

Sleep deprivation can trigger migraine, and migraineurs often choose to sleep to relieve headaches during acute migraine. This study aimed to explore the effect of acute sleep deprivation on hyperalgesia induced by nitroglycerin in mice. In part one, after either 6-hour sleep deprivation or 6-hour normal sleep, mice were intraperitoneally injected with nitroglycerin or saline. The mechanical pain threshold and withdrawal latency of the hindpaw were measured every 30 minutes for 6 hours. Next, the same sleep deprivation and injection procedure was performed with new mice, and mice were sacrificed 4.5 hours after injection. The trigeminal nucleus caudalis and upper cervical spinal segments were taken for immunofluorescence Fos staining. In part two, after injection of saline or nitroglycerin, the mice were either deprived of sleep for 6 hours or allowed to sleep without interference. The mechanical and thermal pain threshold were measured after 6 hours. In part three, we compared the sleep time of mice after intraperitoneal injection of saline or nitroglycerin without interference. Sleep deprivation for 6 hours did not cause any changes in the baseline pain thresholds in mice. However, pretreatment with 6-hour sleep deprivation significantly prolonged the duration of hyperalgesia induced by nitroglycerin. Additionally, the expression of Fos at 4.5 hours was significantly higher in the 6-hour sleep deprivation and nitroglycerin group than in the other three groups. When intraperitoneal injection was given first, the mechanical pain threshold of the hind paw was significantly lower in the group that received nitroglycerin with 6-hour sleep deprivation than in the other groups. Compared to the saline injection, one-time nitroglycerin injection would result in a significant increase in sleep latency and decrease in sleep duration for the normal mice. Acute sleep deprivation significantly aggravated the hyperalgesia induced by nitroglycerin in mice, which highlights the importance of sleep disorders for migraine.

Rheumatoid arthritis is a chronic condition that is characterized by joint pain and inflammation. It is an autoimmune disorder in which the body tissues are erroneously attacked by the immune system of the host itself. It has been evident that rheumatoid arthritis symptoms follow a 24 h circadian rhythm and exhibit high thresholds of pain, functional disability, and stiffness predominantly early in the morning. Colon-specific drug delivery systems can be utilized in the formulations to be used in the treatment of rheumatoid arthritis. The colon-specific drug delivery system has shown promising results in the treatment of different diseases at the colonic site like Crohn's disease, ulcerative colitis, colon cancer, etc. The colon-specific drug delivery is capable of delivering the formulation at the predetermined location and predetermined time. The early morning symptoms of rheumatoid arthritis like pain and inflammation can be treated using the various approaches of the colon-specific drug delivery system because it will lead to patient compliance as the patient will not require administering the formulation immediately after waking up in the morning. This review also explains the immunological factors which may trigger rheumatoid arthritis in human beings. It further explores conventional approaches like pH-dependant, microorganisms-driven, pressure-controlled, and time-dependant formulations. By employing two or more conventional approaches given above the various novel approaches have been designed to eliminate the drawbacks of individual techniques.