Pain pathway

Neuropathic pain can occur during the prediabetic stage, even in the absence of hyperglycemia. The presence of prediabetic neuropathic pain (PDNP) poses challenges to the management of individuals with prediabetes. However, the mechanisms underlying this pain remain unclear. This study aims to investigate the underlying mechanism and identify potential therapeutic targets of PDNP. A prediabetic animal model induced by a high-energy diet exhibits both mechanical allodynia and thermal hyperalgesia. Furthermore, hyperexcitability and decreased potassium currents are observed in the dorsal root ganglion (DRG) neurons of these rats...

INTRODUCTION: Small fiber neuropathy (SFN) is a common cause of neuropathic pain in peripheral neuropathies. Good accessibility of diagnostics and treatment is necessary for an accurate diagnosis and treatment of SFN. Evidence is lacking on the quality performance of the diagnostic SFN service in the Netherlands. Our aim was to determine the patient satisfaction and -accessibility of the diagnostic SFN service, and to identify areas for improvement. METHODS: In a single-center, prospective, survey-based cohort study, 100 visiting patients were asked to fill in the SFN patient satisfaction questionnaire (SFN-PSQ), with 10 domains and 51 items...

UNLABELLED: Osteoporosis-pseudoglioma syndrome (OPPG) and LRP5 high bone mass (LRP5-HBM) are two rare bone diseases with opposite clinical symptoms caused by loss-of-function and gain-of-function mutations in LRP5. Bisphosphonates are an effective treatment for OPPG patients. LRP5-HBM has a benign course, and age-related bone loss is found in one LRP5-HBM patient. PURPOSE: Low-density lipoprotein receptor-related protein 5 (LRP5) is involved in the canonical Wnt signaling pathway...

Uterine leiomyosarcoma is a rare malignant gynecologic tumor that arises from the myometrial or endometrial stromal precursor cells. This tumor has the highest prevalence in the pre- and post-is more frequent between 40 and 60 years old. It has a very unfavorable prognosis: only early-stage tumors have an acceptable prognosis; unfortunately, it is often diagnosed accidentally, typically on an advanced stage, when hematological metastases have already spread. Surgery is the main treatment strategy, while systemic treatment and radiotherapy are not recommended due to the lack of results...

Obesity is a growing global health crisis intricately connected to various chronic conditions, including arthritis. This paper explores the intricate web of hormonal changes in the context of obesity and their profound influence on the development and progression of arthritis. Hormones, such as leptin, insulin, cortisol, and estrogen, all altered in obesity, play pivotal roles in inflammation, cartilage degradation, mechanical stress, and pain associated with obesity-related arthritis. Additionally, the mechanical stress placed on weight-bearing joints by excess body weight accelerates joint wear and tear, contributing to arthritis...

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This study aims to explore the mechanism of aqueous extract of Strychni Semen(SA) in relieving pain in the rat model of rheumatoid arthritis(RA) via Toll-like receptor 4(TLR4)/tumor necrosis factor-α(TNF-α)/matrix metalloproteinase-9(MMP-9) signaling pathway. Firstly, the main chemical components of Strychni Semen were searched against TCMSP, TCMID, ETCM, and related literature, and the main targets of the chemical components were retrieved from TargetNet and SwissTargetPrediction. The main targets of RA and pain were searched against GeneCards, Online Mendelian Inheritance in Man(OMIM), and Therapeutic Target Database(TTD)...

ETHNOPHARMACOLOGICAL RELEVANCE: Acute Gouty Arthritis (AGA) is characterized by a rapid inflammatory reaction caused by the build-up of monosodium urate (MSU) crystals in the tissues surrounding the joints. This condition often associated with hyperuricemia, is distinguished by its symptoms of intense pain, active inflammation, and swelling of the joints. Traditional approaches in AGA management often fall short of desired outcomes in clinical settings. However, recent ethnopharmacological investigations have been focusing on the potential of Traditional Herbal Medicine (THM) in various forms, exploring their therapeutic impact and targets in AGA treatment...

BACKGROUND: Diabetic neuropathy (DN) is the most common complication of diabetes, and approximately 50% of patients with this disease suffer from peripheral neuropathy. Nerve fiber loss in DN occurs due to myelin defects and is characterized by symptoms of impaired nerve function. Schwann cells (SCs) are the main support cells of the peripheral nervous system and play important roles in several pathways contributing to the pathogenesis and development of DN. We previously reported that human tonsil-derived mesenchymal stem cells differentiated into SCs (TMSC-SCs), named neuronal regeneration-promoting cells (NRPCs), which cells promoted nerve regeneration in animal models with peripheral nerve injury or hereditary peripheral neuropathy...

INTRODUCTION: Orthopedic surgeons are the third highest prescribers of narcotics. Previous work demonstrated that surgeons prescribe three times the narcotics required, and most patients do not properly dispose of leftover medication following surgery. This has prompted the creation of multimodal pain regimens to reduce reliance on narcotics. It is unknown if these pathways can effectively eliminate opioids following total knee arthroplasty (TKA). Our purpose was to evaluate a multimodal regimen without schedule II narcotics following TKA, in a randomized, blinded fashion...

BACKGROUND: Patients with irritable bowel syndrome with constipation (IBS-C) experience persistent abdominal pain, a common symptom leading to greater healthcare utilization and reports of treatment non-response. Clinically significant improvements in abdominal pain were observed in clinical trials of tenapanor, a first-in-class inhibitor of sodium/hydrogen exchanger isoform 3 (NHE3), for the treatment of IBS-C in adults. AIM: This narrative review reports the current knowledge about visceral hypersensitivity as a mechanism for abdominal pain in patients with IBS-C and explores the published evidence for hypothesized mechanisms by which tenapanor may reduce visceral hypersensitivity leading to the observed clinical response of decreased abdominal pain...

The thalamus and its cortical connections play a pivotal role in pain information processing, yet the exploration of its electrophysiological responses to nociceptive stimuli has been limited. Here, in 2 experiments we recorded neural responses to nociceptive laser stimuli in the thalamic (ventral posterior lateral nucleus and medial dorsal nucleus) and cortical regions (primary somatosensory cortex [S1] and anterior cingulate cortex) within the lateral and medial pain pathways. We found remarkable similarities in laser-evoked brain responses that encoded pain intensity within thalamic and cortical regions...

Phosphodiesterases (PDEs) are vital in signal transduction, specifically by hydrolyzing cAMP and cGMP. Within the PDE family, PDE10A is notable for its prominence in the striatum and its regulatory function over neurotransmitters in medium-spiny neurons. Given the dopamine deficiency in Parkinson's disease (PD) that affects striatal pathways, PDE10A inhibitors could offer therapeutic benefits by modulating D1 and D2 receptor signaling. This study was motivated by the successful history of quinazoline/quinazoline scaffolds in the inhibition of PDE10A...

BACKGROUND AND PURPOSE: The spinal cord is a key structure involved in the transmission and modulation of pain. Pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP), are expressed in the spinal cord. These peptides activate G protein-coupled receptors (PAC1 , VPAC1 and VPAC2 ) that could provide targets for the development of novel pain treatments. However, it is not clear which of these receptors are expressed within the spinal cord and how these receptors signal...

Neuropathic pain (NP) is a prevalent condition often associated with heightened pain responsiveness suggestive of central sensitization. Neuroimaging biomarkers of treatment outcomes may help develop personalised treatment strategies, but white matter (WM) properties have been under-explored for this purpose. Here we assessed whether WM pathways of the default mode network (DMN: medial prefrontal cortex (mPFC), posterior cingulate cortex (PCC), precuneus (PCu)) and descending pain modulation system (periaqueductal gray (PAG)) are associated with ketamine analgesia and attenuated temporal summation of pain (TSP, reflecting central sensitization) in NP...

ETHNOPHARMACOLOGICAL RELEVANCE: Shentong Zhuyu Decoction (STZYD) is a traditional prescription for promoting the flow of Qi and Blood which is often used in the treatment of low back and leg pain clinicall with unclear mechanism. Neuropathic pain (NP) is caused by disease or injury affecting the somatosensory system. LncRNAs may play a key role in NP by regulating the expression of pain-related genes through binding mRNAs or miRNAs sponge mechanisms. AIM OF THE STUDY: To investigate the effect and potential mechanism of STZYD on neuropathic pain...

OBJECTIVES: Trigeminal neuralgia (TN) is a severe chronic neuropathic pain that mainly affects the distribution area of the trigeminal nerve with limited treating efficacy. There are numerous treatments for TN, but currently the main clinical approach is to suppress pain by carbamazepine (CBZ). Brain-derived neurotrophic factor (BDNF) is closely related to chronic pain. This study aims to determine the effects of CBZ treatment on BDNF expression in both the trigeminal ganglion (TG) and serum of TN via a chronic constriction injury of the infraorbital nerve (ION-CCI) rat model...

As the management of acute pain for children undergoing surgical procedures as well as recognition of the short and long term risks of exposure to opioids has evolved, multimodal and multidisciplinary approaches using organized pathways has resulted in improved perioperative outcomes and patient satisfaction. In this 2023 symposium held at the American Academy of Pediatrics on Surgery meeting, a multidisciplinary discussion on current enhanced recovery after surgery pathways, alternate methods of effective pain control and education and advocacy efforts for opioid reduction were discussed, and highlights are included in this article...

Inflammatory Bowel Diseases (IBD) cause diarrhea and abdominal pain that impair quality of life. Digestive damage frequently leads to undernutrition and sarcopenia, which worsen the prognosis of the disease. This led to the development of PROACTIVE, a multimodal prehabilitation program designed to improve the functional capacities, nutritional status and quality of life of IBD patients. 19 patients have been included in our pilot program, with an initial personalized multimodal assessment, 10 group sessions with 4 patients, and a final multimodal assessment proposing personalized care for home...

The pancreas is a heterocrine gland that has both exocrine and endocrine parts. Most pancreatic cancer begins in the cells that line the ducts of the pancreas and is called pancreatic ductal adenocarcinoma (PDAC). PDAC is the most encountered pancreatic cancer type. One of the most important characteristic features of PDAC is neuropathy which is primarily due to perineural invasion (PNI). PNI develops tumor microenvironment which includes overexpression of fibroblasts cells, macrophages, as well as angiogenesis which can be responsible for neuropathy pain...