VCP controls KCC2 degradation through FAF1 recruitment and accelerates emergence from anesthesia.

Ubiquitin-proteasomal degradation of K/Cl cotransporter 2 (KCC2) in the ventral posteromedial nucleus (VPM) has been demonstrated to serve as a common mechanism by which the brain emerges from anesthesia and regains consciousness. Ubiquitin-proteasomal degradation of KCC2 during anesthesia is driven by E3 ligase Fbxl4. However, the mechanism by which ubiquitinated KCC2 is targeted to the proteasome has not been elucidated.

Blocking proteinase-activated receptor 2 signaling relieves pain, suppresses nerve sprouting, improves tissue repair, and enhances analgesic effect of B vitamins in rats with Achilles tendon injury.

Tendon injury produces intractable pain and disability in movement, but the medications for analgesia and restoring functional integrity of tendon are still limited. In this study, we report that proteinase-activated receptor 2 (PAR2) activation in dorsal root ganglion (DRG) neurons contributes to chronic pain and tendon histopathological changes produced by Achilles tendon partial transection injury (TTI). Tendon partial transection injury increases the expression of PAR2 protein in both somata of DRG neurons and their peripheral terminals within the injured Achilles tendon.

Diabetic Neuropathic Pain: Directions for Exploring Treatments.

Diabetic neuropathic pain (DNP) is one of the common and severe late-stage complications of diabetes mellitus, which could greatly influence the patients' quality of life. Patients with DNP often experience spontaneous pain and evoked pain such as mechanical allodynia and thermal hyperalgesia, meaning that their physical and psychological health are severely impaired. Unfortunately, the mechanisms of DNP remain highly elusive, so substantial breakthrough in effective DNP targeted treatments is still clinically challenging.

Neurobiological basis of emergence from anesthesia.

The suppression of consciousness by anesthetics and the emergence of the brain from anesthesia are complex and elusive processes. Anesthetics may exert their inhibitory effects by binding to specific protein targets or through membrane-mediated targets, disrupting neural activity and the integrity and function of neural circuits responsible for signal transmission and conscious perception/subjective experience. Emergence from anesthesia was generally thought to depend on the elimination of the anesthetic from the body.

Vitamins in neuropathy: pathophysiological and therapeutic roles.

Purpose Of Review: Vitamin deficiency is a risk factor in the development of peripheral neuropathy, which leads to complex and severe diseases. This review provides an update overview of the literature on the roles of vitamins in peripheral neuropathy, highlighting their pathophysiological and therapeutic roles.

Recent Findings: The importance and clinical manifestations and implications of the vitamins and vitamin deficiencies are further demonstrated in peripheral neuropathy and the associated diseases.

Lactobacillus rhamnosus GG and butyrate supplementation in rats with bone cancer reduces mechanical allodynia and increases expression of μ-opioid receptor in the spinal cord.

Introduction: Chronic cancer pain is one of the most unbearable symptoms for the patients with advanced cancer. The treatment of cancer pain continues to possess a major challenge. Here, we report that adjusting gut microbiota via probiotics can reduce bone cancer pain (BCP) in rats.

Characterization of Inflammatory Signals in BV-2 Microglia in Response to Wnt3a.

Activation of microglia is one of the pathological bases of neuroinflammation, which involves various diseases of the central nervous system. Inhibiting the inflammatory activation of microglia is a therapeutic approach to neuroinflammation. In this study, we report that activation of the Wnt/β-catenin signaling pathway in a model of neuroinflammation in Lipopolysaccharide (LPS)/IFN-γ-stimulated BV-2 cells can result in inhibition of production of nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α).

Emergence of consciousness from anesthesia through ubiquitin degradation of KCC2 in the ventral posteromedial nucleus of the thalamus.

The emergence of consciousness from anesthesia, once assumed to be a passive process, is now considered as an active and controllable process. In the present study, we show in mice that, when the brain is forced into a minimum responsive state by diverse anesthetics, a rapid downregulation of K/Cl cotransporter 2 (KCC2) in the ventral posteromedial nucleus (VPM) serves as a common mechanism by which the brain regains consciousness. Ubiquitin-proteasomal degradation is responsible for KCC2 downregulation, which is driven by ubiquitin ligase Fbxl4.

Gut microbiota depletion by antibiotics ameliorates somatic neuropathic pain induced by nerve injury, chemotherapy, and diabetes in mice.

Background: Gut microbiota has been found involved in neuronal functions and neurological disorders. Whether and how gut microbiota impacts chronic somatic pain disorders remain elusive.

Methods: Neuropathic pain was produced by different forms of injury or diseases, the chronic constriction injury (CCI) of the sciatic nerves, oxaliplatin (OXA) chemotherapy, and streptozocin (STZ)-induced diabetes in mice.

Differential Activation of pERK1/2 and c-Fos Following Injury to Different Regions of Primary Sensory Neuron.

Nerve injury causes hyperexcitability of the dorsal root ganglion (DRG) and spinal dorsal horn (DH) neurons, which results in neuropathic pain. We have previously demonstrated that partial dorsal rhizotomy (PDR) produced less severe pain-like behavior than chronic constriction injury (CCI) or chronic compression of DRG (CCD) and did not enhance DRG neuronal excitability. However, the mechanisms underlying such discrepancy remain unclear.

Role of Matrix Metalloproteinases in Myelin Abnormalities and Mechanical Allodynia in Rodents with Diabetic Neuropathy.

The treatment of diabetic neuropathic pain (DNP) is a major clinical challenge. The underlying mechanisms of diabetic neuropathy remain unclear, and treatment approaches are limited. Here, we report that the gelatinases MMP-9 and MMP-2 play a critical role in axonal demyelination and DNP in rodents.

Self-Healing: A Concept for Musculoskeletal Body Pain Management - Scientific Evidence and Mode of Action.

Traditionally, musculoskeletal pain management has focused on the use of conventional treatments to relieve pain. However, multi-modal integrative medicine including alternative/complementary treatments is becoming more widely used and integrated into treatment guidelines around the world. The uptake of this approach varies according to country, with generally a higher uptake in developed countries and in females aged more than 40 years.

Spinal beta-amyloid1-42 acts as an endogenous analgesic peptide in CCI-induced neuropathic pain.

Background: The mechanism for reduced pain sensitivity associated with Alzheimer's disease (AD) has not been illustrated. We hypothesize that amyloid beta 1-42 (Aβ1-42) in the spinal cord acts as an endogenous analgesic peptide to suppress pain induced by nerve injury.

Methods: We used chronic constriction injury of the sciatic nerve (CCI) to produce neuropathic pain in Sprague-Dawley rats.

Distinct Gene Expression Patterns of Ion Channels and Cytokines in Rat Primary Sensory Neurons During Development of Bone Cancer and Cancer Pain.

Cancer and cancer pain processes a major clinical challenge and the underlined mechanisms of pathogenesis remain elusive. We examined the specific changes in the transcriptomic profiles in the dorsal root ganglion (DRG) neurons of rats with bone cancer and bone cancer pain (BCP) using RNA sequencing technology. The bone cancer and BCP was induced by tumor cells implantation (TCI) into the tibia bone cavity in adult female rats.

Pain during and after coronavirus disease 2019: Chinese perspectives.

The coronavirus disease 2019 (COVID-19) global pandemic poses a major threat to human health and health care systems. Urgent prevention and control measures have obstructed patients' access to pain treatment, and many patients with pain have been unable to receive adequate and timely medical services. Many patients with COVID-19 report painful symptoms including headache, muscle pain, and chest pain during the initial phase of the disease.

B vitamins as a treatment for diabetic pain and neuropathy.

What Is Known And Objective: B vitamin therapy is a common treatment for diabetic pain and neuropathy, yet its use remains controversial in patients lacking B vitamin deficiencies. The aim of this review was to summarize the current evidence for the efficacy of B vitamin therapy in diabetic patients with neuropathy.

Comment: We screened the English literature for clinical studies evaluating B vitamins as a therapy for pain and neuropathy in diabetic patients.

The revised International Association for the Study of Pain definition of pain: concepts, challenges, and compromises.

The current International Association for the Study of Pain (IASP) definition of pain as "An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage" was recommended by the Subcommittee on Taxonomy and adopted by the IASP Council in 1979. This definition has become accepted widely by health care professionals and researchers in the pain field and adopted by several professional, governmental, and nongovernmental organizations, including the World Health Organization. In recent years, some in the field have reasoned that advances in our understanding of pain warrant a reevaluation of the definition and have proposed modifications.

Activation of EphB receptors contributes to primary sensory neuron excitability by facilitating Ca2+ influx directly or through Src kinase-mediated N-methyl-D-aspartate receptor phosphorylation.

EphrinB-EphB receptor tyrosine kinases have been demonstrated to play important roles in pain processing after peripheral nerve injury. We have previously reported that ephrinB-EphB receptor signaling can regulate excitability and plasticity of neurons in spinal dorsal horn, and thus contribute to spinal central sensitization in neuropathic pain. How EphB receptor activation influences excitability of primary neurons in dorsal root ganglion (DRG), however, remains unknown.

Systematic Administration of B Vitamins Alleviates Diabetic Pain and Inhibits Associated Expression of P2X3 and TRPV1 in Dorsal Root Ganglion Neurons and Proinflammatory Cytokines in Spinal Cord in Rats.

Background: Treatment of diabetic neuropathic pain (DNP) continues to be a major challenge, and underlying mechanisms of DNP remain elusive. We investigated treatment effects of B vitamins on DPN- and DNP-associated alterations of neurochemical signaling in the nociceptive dorsal root ganglion (DRG) neurons and the spinal cord in rats.

Methods: DNP was produced in male, adult, Sprague Dawley rats by single i.

IFNβ Treatment Inhibits Nerve Injury-induced Mechanical Allodynia and MAPK Signaling By Activating ISG15 in Mouse Spinal Cord.

Neuropathic pain is difficult to treat and remains a major clinical challenge worldwide. While the mechanisms which underlie the development of neuropathic pain are incompletely understood, interferon signaling by the immune system is known to play a role. Here, we demonstrate a role for interferon β (IFNβ) in attenuating mechanical allodynia induced by the spared nerve injury in mice.

Wnt signaling contributes to withdrawal symptoms from opioid receptor activation induced by morphine exposure or chronic inflammation.

Preventing and treating opioid dependence and withdrawal is a major clinical challenge, and the underlying mechanisms of opioid dependence and withdrawal remain elusive. We hypothesized that prolonged morphine exposure or chronic inflammation-induced μ-opioid receptor activity serves as a severe stress that elicits neuronal alterations and recapitulates events during development. Here, we report that Wnt signaling, which is important in developmental processes of the nervous system, plays a critical role in withdrawal symptoms from opioid receptor activation in mice.

Cyclic nucleotide signaling in sensory neuron hyperexcitability and chronic pain after nerve injury.

The cyclic nucleotide signaling, including cAMP-PKA and cGMP-PKG pathways, has been well known to play critical roles in regulating cellular growth, metabolism and many other intracellular processes. In recent years, more and more studies have uncovered the roles of cAMP and cGMP in the nervous system. The cAMP and cGMP signaling mediates chronic pain induced by different forms of injury and stress.