dorsal horn neurons

Patients with systemic lupus erythematosus (SLE) frequently experience chronic pain due to the limited effectiveness and safety profiles of current analgesics. Understanding the molecular and synaptic mechanisms underlying abnormal neuronal activation along the pain signaling pathway is essential for developing new analgesics to address SLE-induced chronic pain. Recent studies, including those conducted by our team and others using the SLE animal model ( MRL / lpr lupus-prone mice), have unveiled heightened excitability in nociceptive primary sensory neurons within the dorsal root ganglia and increased glutamatergic synaptic activity in spinal dorsal horn neurons, contributing to the development of chronic pain in mice with SLE...

The dorsal root ganglion (DRG) serves as a pivotal site for managing chronic pain through dorsal root ganglion stimulation (DRG-S). In recent years, the DRG-S has emerged as an attractive modality in the armamentarium of neuromodulation therapy due to its accessibility and efficacy in alleviating chronic pain refractory to conventional treatments. Despite its therapeutic advantages, the precise mechanisms underlying DRG-S-induced analgesia remain elusive, attributed in part to the diverse sensory neuron population within the DRG and its modulation of both peripheral and central sensory processing pathways...

Photobiomodulation (PBM) has attracted attention as a treatment for chronic pain. Previous studies have reported that PBM of the sciatic nerve inhibits neuronal firing in the superficial layers (lamina I-II) of the spinal dorsal horn of rats, which is evoked by mechanical stimulation that corresponds to noxious stimuli. However, the effects of PBM on the deep layers (lamina III-IV) of the spinal dorsal horn, which receive inputs from innocuous stimuli, remain poorly understood. In this study, we examined the effect of PBM of the sciatic nerve on firing in the deep layers of the spinal dorsal horn evoked by mechanical stimulation...

Opioid pain medications, such as morphine, remain the mainstay for treating severe and chronic pain. Prolonged morphine use, however, triggers analgesic tolerance and hyperalgesia (OIH), which can last for a long period after morphine withdrawal. How morphine induces these detrimental side effects remains unclear. Here, we show that morphine tolerance and OIH are mediated by Tiam1-coordinated synaptic structural and functional plasticity in the spinal nociceptive network. Tiam1 is a Rac1 GTPase guanine nucleotide exchange factor (GEF) that promotes excitatory synaptogenesis by modulating actin cytoskeletal dynamics...

Huntington's disease (HD), referred to as Huntington's chorea, is an infrequent neurodegenerative ailment with an autosomal-dominant inheritance pattern characterized by the progressive deterioration of GABAergic neurons in the basal ganglia. Other ones include subcortical-type dementia, behavioral abnormalities, midlife psychosis, and gradual inadvertent choreoathetosis movements. HD is characterized by atrophy of the dorsal striatum (caudate nucleus and putamen) with concurrent expansion of the frontal horns of the lateral ventricles on imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI)...

Distribution of endomorphin-1 (EM-1) was immunohistochemically investigated in the rat cranial sensory ganglia. Small to medium-sized neurons in the trigeminal (TG), petrosal (PG), and jugular ganglia (JG) expressed EM-1-immunoreactivity. However, EM-1-immunoreactive (-ir) neurons were infrequent in the nodose ganglion. In the brainstem, EM-1-ir varicose fibers were detected in the superficial layer of the medullary dorsal horn and the caudal part of the nucleus tractus solitarius. By trichrome immunofluorescence analysis, approximately 70% of EM-1-ir neurons were also immunoreactive for transient receptor potential vanilloid 1 (TRPV1) in all the examined ganglia...

Diabetic neuropathy is the most common complication of diabetes and lacks effective treatments. Although sensory dysfunction during the early stages of diabetes has been extensively studied in various animal models, the functional and morphological alterations in sensory and motor systems during late stages of diabetes remain largely unexplored. In the current work, we examined the influence of diabetes on sensory and motor function as well as morphological changes in late stages of diabetes. The obese diabetic Leprdb/db mice (db/db) were used for behavioral assessments and subsequent morphological examinations...

In pilot work we showed that somatic nerve transfers can restore motor function in long-term decentralized dogs. We continue to explore the effectiveness of motor reinnervation in 30 female dogs. After anesthesia, 12 underwent bilateral transection of coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7, and hypogastric nerves. Twelve months post-decentralization, 8 underwent transfer of obturator nerve branches to pelvic nerve vesical branches, and sciatic nerve branches to pudendal nerves, followed by 10 months recovery (ObNT-ScNT Reinn)...

The management and therapy of bone cancer pain (BCP) remain formidable clinical challenges. Curcumin and its analogues have been shown to have anti-inflammatory and analgesic properties. In the present study, we investigated the efficacy of curcumin analogue NL04 (NL04) in modulating inflammation in spinal dorsal horn (SDH), thereby exploring its potential to reduce central sensitization of BCP in a rat model. Differing doses of NL04 and curcumin were administered intrathecally either once (on day 12 of BCP) or over seven consecutive days (from day 6-12 of BCP)...

The monosynaptic connection from the lateral parabrachial nucleus (LPB) to the central amygdala (CeA) serves as a fundamental pathway for transmitting nociceptive signals to the brain. The LPB receives nociceptive information from the dorsal horn and spinal trigeminal nucleus and sends it to the "nociceptive" CeA, which modulates pain-associated emotions and nociceptive sensitivity. To elucidate the role of densely expressed mu-opioid receptors (MORs) within this pathway, we investigated the effects of exogenously applied opioids on LPB-CeA synaptic transmission, employing optogenetics in mice expressing channelrhodopsin-2 in LPB neurons with calcitonin gene-related peptide (CGRP)...

Postamputation pain is currently managed unsatisfactorily with neuron-targeted pharmacological and interventional therapies. Non-neuronal pain mechanisms have emerged as crucial factors in the development and persistence of post-amputation pain. Consequently, these mechanisms offer exciting prospects as innovative therapeutic targets. We examined the hypothesis that engaging mesenchymal stem cells (MSCs) would foster local neuroimmune interactions, leading to a potential reduction in post-amputation pain. We utilized an ex vivo neuroma model from a phantom limb pain patient to uncover that the oligodeoxynucleotide IMT504 engaged human primary MSCs to promote an anti-inflammatory microenvironment...

Recent transcriptomic studies identified Gucy2d (encoding guanylate cyclase D) as a highly enriched gene within inhibitory dynorphin interneurons in the mouse spinal dorsal horn. To facilitate investigations into the role of the Gucy2d+ population in somatosensation, Gucy2d-cre transgenic mice were created to permit chemogenetic or optogenetic manipulation of this subset of spinal neurons. Gucy2d-cre mice created via CRISPR/Cas9 genomic knock-in were bred to mice expressing a cre-dependent reporter (either tdTomato or Sun1...

INTRODUCTION: Sustained opioid use has long-term negative impacts on future pain experience, particularly in women. This study aimed to investigate the underlying spinal neurobiology of this clinical observation in an experimental model of joint pain. OBJECTIVES: In this study, we tested the hypothesis that sustained opioid treatment exacerbates chronic pain responses and alters spinal cord dorsal horn astrogliosis and the expression of GluN2B-containing N-methyl-d-aspartate receptors in female rats...

Pathological pain emerges from nociceptive system dysfunction, resulting in heightened pain circuit activity. Various forms of circuitry plasticity, such as central sensitization, synaptic plasticity, homeostatic plasticity, and excitation/inhibition balance, contribute to the malfunction of neural circuits during pain pathogenesis. Recently, a new form of plasticity in the spinal dorsal horn (SDH), named neural circuit polarization (NCP), was discovered in pain models induced by HIV-1 gp120 and chronic morphine administration...

Spinal cord injury (SCI) leads to the development of neuropathic pain. Although a multitude of pathological processes contribute to SCI-induced pain, excessive intracellular calcium accumulation and voltage-gated calcium-channel upregulation play critical roles in SCI-induced pain. However, the role of calcium-channel blockers in SCI-induced pain is unknown. Omega-conotoxin MVIIA (MVIIA) is a calcium-channel blocker that selectively inhibits N-type voltage-dependent calcium channels and demonstrates neuroprotective effects...

Paclitaxel (PTX) is a chemotherapeutic agent that is widely used for the treatment of several types of tumors. However, PTX-induced peripheral neuropathy (PIPN) is an adverse effect generally induced by long-term PTX use that significantly impairs the quality of life. Necroptosis has been implicated in various neurodegenerative disorders. Necroptosis of dorsal root ganglion neurons triggers the pathogenesis of PIPN. Therefore, the present study aims to investigate the role of spinal neuronal necroptosis in PIPN...

Sensory feedback is integral for contextually appropriate motor output, yet the neural circuits responsible remain elusive. Here, we pinpoint the medial deep dorsal horn of the mouse spinal cord as a convergence point for proprioceptive and cutaneous input. Within this region, we identify a population of tonically active glycinergic inhibitory neurons expressing parvalbumin. Using anatomy and electrophysiology, we demonstrate that deep dorsal horn parvalbumin-expressing interneuron (dPV) activity is shaped by convergent proprioceptive, cutaneous, and descending input...

Anandamide (AEA) is an important modulator of nociception in the spinal dorsal horn, acting presynaptically through Cannabinoid (CB1 ) and Transient receptor potential vanilloid (TRPV1) receptors. The role of AEA (1 µM, 10 µM, and 30 µM) application on the modulation of nociceptive synaptic transmission under control and inflammatory conditions was studied by recording miniature excitatory postsynaptic currents (mEPSCs) from neurons in spinal cord slices. Inhibition of the CB1 receptors by PF514273, TRPV1 by SB366791, and the fatty acid amide hydrolase (FAAH) by URB597 was used...

The dorsal spinal cord is crucial for the transmission and modulation of multiple somatosensory modalities, such as itch, pain, and touch. Despite being essential for the well-being and survival of an individual, itch and pain, in their chronic forms, have increasingly been recognized as clinical problems. Although considerable progress has been made in our understanding of the neurochemical processing of nociceptive and chemical itch sensations, the neural substrate that is crucial for mechanical itch processing is still unclear...

ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis, the dried and ripe fruit of the magnolia family plant Schisandra chinensis (Turcz.) Baill, was commonly used in traditional analgesic prescription. Studies have shown that the extract of Schisandra chinensis (SC) displayed analgesic activity. However, the analgesic active component and the exact mechanisms have yet to be revealed. AIM OF THE STUDY: The present study was to investigate the anti-nociceptive constituent of Schisandra chinensis, assess its analgesic effect, and explore the potential molecular mechanisms...