NFAT1 Orchestrates Spinal Microglial Transcription and Promotes Microglial Proliferation via c-MYC Contributing to Nerve Injury-Induced Neuropathic Pain.

Peripheral nerve injury-induced spinal microglial proliferation plays a pivotal role in neuropathic pain. So far, key intracellular druggable molecules involved in this process are not identified. The nuclear factor of activated T-cells (NFAT1) is a master regulator of immune cell proliferation.

Plasticity of neuronal excitability and synaptic balance in the anterior nucleus of paraventricular thalamus after nerve injury.

The anterior nucleus of the paraventricular thalamus (aPVT) integrates various synaptic inputs and conveys information to the downstream brain regions for arousal and pain regulation. Recent studies have indicated that the PVT plays a crucial role in the regulation of chronic pain, but the plasticity mechanism of neuronal excitability and synaptic inputs for aPVT neurons in neuropathic pain remains unclear. Here, we report that spinal nerve ligation (SNL) significantly increased the neuronal excitability and reset the excitatory/inhibitory (E/I) synaptic inputs ratio of aPVT neurons in mice.

Ultrasound-guided Cervical Retro-laminar Block for Cervical Radicular Pain: A Comparative Analysis.

Study Design And Objective: Cervical radiculopathy is a common clinical condition, often treated with cervical epidural steroid injections (ESI). Retro-laminar cervical blocks (RLCB) may be considered safer than ESI as they do not require entering the neuroaxis.In this study, we evaluated the outcome of RLCB in patients with cervical radiculopathy who had failed conservative treatment and were candidates for cervical spine decompression surgery.

Decoding gene expression signatures in mice trigeminal ganglion across trigeminal neuropathic pain stages via high-throughput sequencing.

Trigeminal neuropathic pain (TNP) arises due to peripheral nerve injury, the mechanisms underlying which are little known. The altered gene expression profile in sensory ganglia is critical for neuropathic pain generation and maintenance. We, therefore, assessed the transcriptome of the trigeminal ganglion (TG) from mice at different periods of pain progression.

Short- and long-term effects of conventional spinal cord stimulation on chronic pain and health perceptions: A longitudinal controlled trial.

Background: The effectiveness and long-term outcomes of spinal cord stimulation (SCS) are not fully established, especially considering that data from patients who withdrew from the trial are rarely analysed, which may lead to overestimation of SCS efficacy. We evaluated short- and long-term effects of SCS on chronic pain and perceived health, beyond natural variability in these outcomes.

Methods: In a prospective design, 176 chronic pain patients referred to SCS were evaluated five times (baseline; retest ~6 weeks later; post-SCS trial; 8 and 28 weeks post-permanent implantation).

Effect of Implantable Electrical Nerve Stimulation on Cortical Dynamics in Patients With Herpes Zoster-Related Pain: A Prospective Pilot Study.

Implantable electrical nerve stimulation (ENS) can be used to treat neuropathic pain caused by herpes zoster. However, little is known about the cortical mechanism underlying neuromodulation therapy. Here, we recorded a 16-channel resting-state electroencephalogram after the application of spinal cord stimulation ( = 5) or peripheral nerve stimulation ( = 3).

Feasibility of Magnetic Resonance-Guided High-Intensity-Focused Ultrasound (MRgHIFU) Ablation of Stump Neuromas for the Relief of Chronic Postamputation Neuropathic Pain.

Up to 70% of limb amputees develop chronic postamputation neuropathic pain (CPANP) which includes phantom pain and residual limb neuropathic pain due to neuroma formation. CPANP often requires invasive procedures aimed at neuroma ablation. Five amputees received 6 noninvasive magnetic resonance-guided high-intensity-focused ultrasound MRgHIFU treatments ExAblate®, Insightec, Tirat-Carmel, Israel).

Long-term effectiveness and safety of medical cannabis administered through the metered-dose Syqe Inhaler.

Introduction: Preliminary clinical studies on medical cannabis (MC) treatment using the Syqe Inhaler showed short-term effectiveness and safety at very low and precise doses of MC.

Objectives: Here, we retrospectively analyzed "real-life" long-term data collected in real time on the potential effectiveness and safety of MC administered with this device.

Methods: Patients were monitored by Syqe's patient support program.

Abnormal Visual Evoked Responses to Emotional Cues Correspond to Diagnosis and Disease Severity in Fibromyalgia.

Background: Chronic pain disorders are often associated with cognitive-emotional dysregulation. However, the relations between such dysregulation, underlying brain processes, and clinical symptom constellations, remain unclear. Here, we aimed to characterize the abnormalities in cognitive-emotional processing involved in fibromyalgia syndrome (FMS) and their relation to disease severity.

Observation of curative effect on meridian theory-based extracorporeal shock wave therapy for non-specific low back pain: study protocol for a randomized controlled trial.

Background: Non-specific low back pain (NLBP) is a major global socioeconomic burden, and the prevalence of NLBP is still on the rise. At present, there is no ideal drug to cure this disease. This may be the reason why patients often use complementary therapies.

Medical cannabis and stigma: A qualitative study with patients living with chronic pain.

Aims And Objectives: To explore the ways in which stigma is experienced, and what strategies are used to manage stigma among patients using medical cannabis to ease suffering from chronic pain.

Background: Various jurisdictions have legalised medical cannabis in recent decades. Despite increasing prevalence and more liberal attitudes towards medical cannabis, it is possible that patients who use medical cannabis experience stigma.

Increased functional connectivity between limbic brain areas in healthy individuals with high versus low sensitivity to cold pain: A resting state fMRI study.

Background: The representation of variability in sensitivity to pain by differences in neural connectivity patterns and its association with psychological factors needs further investigation. This study assessed differences in resting-state functional connectivity (rsFC) and its association to cognitive-affective aspects of pain in two groups of healthy subjects with low versus high sensitivity to pain (LSP vs. HSP).

Progress on the Elucidation of the Antinociceptive Effect of Ginseng and Ginsenosides in Chronic Pain.

Ginseng (Panax ginseng C.A. Meyer) is a traditional Oriental herbal drug widely used in East Asia.

C/EBPβ Participates in Nerve Trauma-Induced TLR7 Upregulation in Primary Sensory Neurons.

Nerve trauma-induced toll-like receptor 7 (TLR7) expression level increases in primary sensory neurons in injured dorsal root ganglion (DRG) avails to neuropathic pain, but the reason is still unknown. In the current study, we showed that unilateral lumbar 4 (L4) spinal nerve ligation (SNL) upregulated CCAAT/enhancer-binding protein-β (C/EBPβ) expression in ipsilateral L4 DRG. Preventing this elevation attenuated the SNL-induced upregulation of TLR7 in the ipsilateral L4 DRG and inhibited cold/thermal hyperalgesia and mechanical allodynia.

The Role of Transient Receptor Potential A1 and G Protein-Coupled Receptor 39 in Zinc-Mediated Acute and Chronic Itch in Mice.

Itching is a common symptom of many skin or systemic diseases and has a negative impact on the quality of life. Zinc, one of the most important trace elements in an organism, plays an important role in the regulation of pain. Whether and how zinc regulates itching is largely unclear.

Enhanced function of NR2C/2D-containing NMDA receptor in the nucleus accumbens contributes to peripheral nerve injury-induced neuropathic pain and depression in mice.

N-methyl-d-aspartate receptors (NMDARs) dysfunction in the nucleus accumbens (NAc) participates in regulating many neurological and psychiatric disorders such as drug addiction, chronic pain, and depression. NMDARs are heterotetrameric complexes generally composed of two NR1 and two NR2 subunits (NR2A, NR2B, NR2C and NR2D). Much attention has been focused on the role of NR2A and NR2B-containing NMDARs in a variety of neurological disorders; however, the function of NR2C/2D subunits at NAc in chronic pain remains unknown.

Temporal Summation Predicts De Novo Contralateral Pain After Cordotomy in Patients With Refractory Cancer Pain.

Background: Percutaneous cervical cordotomy (PCC), which selectively interrupts ascending nociceptive pathways in the spinal cord, can mitigate severe refractory cancer pain. It has an impressive success rate, with most patients emerging pain-free. Aside from the usual complications of neurosurgical procedures, the risks of PCC include development of contralateral pain, which is less understood.

Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Accelerate Functional Recovery After Spinal Cord Injury by Promoting the Phagocytosis of Macrophages to Clean Myelin Debris.

Macrophage phagocytosis contributes predominantly to processing central nervous system (CNS) debris and further facilitates neurological function restoration after CNS injury. The aims of this study were to evaluate the effect of bone marrow mesenchymal stem cells (BMSC)-derived exosomes (BMSC-Exos) on the phagocytic capability of macrophages to clear myelin debris and to investigate the underlying molecular mechanism during the spinal cord injury (SCI) process. This work reveals that monocyte-derived macrophages (MDMs) infiltrating into the SCI site could efficiently engulf myelin debris and process phagocytic material.

ZNF382 controls mouse neuropathic pain via silencer-based epigenetic inhibition of Cxcl13 in DRG neurons.

Nerve injury-induced changes of gene expression in dorsal root ganglion (DRG) are critical for neuropathic pain genesis. However, how these changes occur remains elusive. Here we report the down-regulation of zinc finger protein 382 (ZNF382) in injured DRG neurons after nerve injury.

CXCR5 down-regulation alleviates cognitive dysfunction in a mouse model of sepsis-associated encephalopathy: potential role of microglial autophagy and the p38MAPK/NF-κB/STAT3 signaling pathway.

Background: Cognitive deficits are common in patients with sepsis. Previous studies in sepsis-associated encephalopathy (SAE) implicated the C-X-C chemokine receptor type (CXCR) 5. The present study used a mouse model of SAE to examine whether CXCR5 down-regulation could attenuate cognitive deficits.

Electrophysiological and Morphological Features of Rebound Depolarization Characterized Interneurons in Rat Superficial Spinal Dorsal Horn.

Substantia gelatinosa (SG) neurons, which are located in the spinal dorsal horn (lamina II), have been identified as the "central gate" for the transmission and modulation of nociceptive information. Rebound depolarization (RD), a biophysical property mediated by membrane hyperpolarization that is frequently recorded in the central nervous system, contributes to shaping neuronal intrinsic excitability and, in turn, contributes to neuronal output and network function. However, the electrophysiological and morphological properties of SG neurons exhibiting RD remain unclarified.