Kilohertz high-frequency spinal cord stimulation (kHF-SCS) is a rapidly advancing neuromodulatory technique in the clinical management of chronic pain. However, the precise cellular mechanisms underlying kHF-SCS-induced paresthesia-free pain relief,...
New strategies for spinal cord stimulation (SCS) for chronic pain have emerged in recent years, which may work better via different analgesic mechanisms than traditional low-frequency (e.g., 50 Hz) paresthesia-based SCS. To determine if 10 kHz and bu...
Windup, a progressive increase in spinal response to repetitive stimulations of nociceptive peripheral fibers, is a useful model to study central sensitization to pain. Windup is expressed by neurons in both the dorsal and ventral horn of the spinal...
Among the myriad of cellular and molecular processes identified as contributing to pathological pain, disinhibition of spinal cord nociceptive signaling to higher cortical centers plays a critical role. Importantly, evidence suggests that impaired gl...
The mechanisms of inflammatory pain need to be identified in order to find new superior treatments. Protease-activated receptors 2 (PAR2) and transient receptor potential vanilloid 1 (TRPV1) are highly co-expressed in dorsal root ganglion neurons and...
Diminished inhibitory control of spinal nociception is one of the major culprits of chronic pain states. Restoring proper synaptic inhibition is a well-established rational therapeutic approach explored by several pharmaceutical companies. A particul...
Significant evidence now suggests that neonatal tissue damage can evoke long-lasting changes in pain sensitivity, but the underlying cellular and molecular mechanisms remain unclear. This review highlights recent advances in our understanding of how...
Neuropathic pain (NPP) is a devastating and unbearable painful condition. As prevailing treatment strategies have failed to mitigate its complications, there remains a demand for effective therapies. Electroacupuncture (EA) has proved a potent remedi...
Boiogito (BO), a Japanese traditional herbal medicine, has been proven to be clinically effective against knee osteoarthritis (KOA)-associated pain. However, the therapeutic mechanism of BO remains unclear. Thus, we investigated the analgesic mechani...
The insular cortex is an important hub for sensory and emotional integration. It is one of the areas consistently found activated during pain. While the insular’s connections to the limbic system might play a role in the aversive and emotional...
Pain transmission at the spinal cord is modulated by noradrenaline (NA)-mediated actions that arise from supraspinal areas. We studied the locus coeruleus (LC) to evaluate the expression of the cathecolamine-synthetizing enzyme tyrosine hydroxylase (...
Upon peripheral nerve injury, vesicular ATP is released from damaged primary afferent neurons. This extracellular ATP subsequently activates purinergic receptors of the spinal cord, which play a critical role in neuropathic pain. As an inhibitor of t...
Sexual dysfunction can be caused by impaired neurotransmission from the peripheral to the central nervous system. Therefore, it is important to evaluate the input of sensory information from the peripheral genital area and investigate the control mec...
We evaluated the mechanisms underlying the spinal cord stimulation (SCS)-induced analgesic effect on neuropathic pain following spared nerve injury (SNI). On day 3 after SNI, SCS was performed for 6 h by using electrodes paraspinally placed on the L4...
Sensory primary afferent fibers, conveying touch, pain, itch, and proprioception, synapse onto spinal cord dorsal horn neurons. Primary afferent central terminals express a wide variety of receptors that modulate glutamate and peptide release. Regula...
Neuropathic pain is more complex and severely affects the quality of patients’ life. However, the therapeutic strategy for neuropathic pain in the clinic is still limited. Previously we have reported that electroacupuncture (EA) has an attenuat...
Our previous studies have revealed the ultrasmall superparamagnetic iron oxide in the amine group USPIO-101 has an analgesic effect on inflammatory pain. Here, we further investigated its effect on the spinal cord and brain via electrophysiological a...
Peripheral nerve injuries induce a pronounced immune reaction within the spinal cord, largely governed by microglia activation in both the dorsal and ventral horns. The mechanisms of activation and response of microglia are diverse depending on the l...
TWIK (tandem-pore domain weak inward rectifying K+)-related spinal cord K+ channel (TRESK), a member of the two-pore domain K+ channel family, is abundantly expressed in dorsal root ganglion (DRG) neurons. It is well documented that TRESK expression...
The molecular mechanisms regulating neurogenesis involve the control of gene expression by transcription factors. Gbx1 and Gbx2, two members of the Gbx family of homeodomain-containing transcription factors, are known for their essential roles in cen...
Phorbol esters are analogues of diacylglycerol which activate C1 domain proteins, such as protein kinase C (PKC). Phorbol ester/PKC pathways have been proposed as potential therapeutic targets for chronic pain states, potentially by phosphorylating p...
Gabapentinoids (gabapentin and pregabalin) and antidepressants (tricyclic antidepressants and serotonin noradrenaline reuptake inhibitors) are often used to treat chronic pain. The descending noradrenergic inhibitory system from the locus coeruleus (...
Spinal microglia are crucial to neuronal hyper-excitability and pain hypersensitivity. The local anesthetic bupivacaine is commonly used for both peripheral and spinal anesthesia. The pain-relief effects resulting from the peripheral and systemic adm...
A complication of diabetes is neuropathic pain, which is difficult to control with medication. We have confirmed that neuropathic pain due to mechanical allodynia in diabetic mice is mediated by a characteristic neuropeptide in the spinal cord. We ev...
Background/Objectives: Chronic pain is a significant global health challenge and is associated with diverse conditions, such as diabetic neuropathic pain and spinal stenosis. Understanding the mechanisms of pain transmission is crucial, for both the...
Pain resulting from metastatic bone disease is a major unmet clinical need. Studying spinal processing in rodent models of cancer pain is desirable since the percept of pain is influenced in part by modulation at the level of the transmission system...
Intraspinal grafting of serotonergic (5-HT) neurons was shown to restore plantar stepping in paraplegic rats. Here we asked whether neurons of other phenotypes contribute to the recovery. The experiments were performed on adult rats after spinal cord...
Intervertebral disc (IVD) degeneration with Modic-like changes is strongly associated with pain. Lack of effective disease-modifying treatments for IVDs with endplate (EP) defects means there is a need for an animal model to improve understanding of...
Painful peripheral neuropathy is a common adverse effect of paclitaxel (PTX) treatment. To analyze the contribution of transient receptor potential vanilloid 1 (TRPV1) in the development of PTX-induced mechanical allodynia/hyperalgesia and thermal hy...
Hyperbaric oxygen (HBO) treatment has been proven to decrease neuroinflammation in rats. This study aimed to determine the potential mechanism underlying the anti-inflammatory effects of HBO treatment on burn-induced neuroinflammation in rats. Thirty...
Gamma-aminobutyric acid (GABA) and glycine act as inhibitory neurotransmitters. Three types of inhibitory neurons and terminals, GABAergic, GABA/glycine coreleasing, and glycinergic, are orchestrated in the spinal cord neural circuits and play critic...
The immune system is involved in the development of neuropathic pain. In particular, the infiltration of T-lymphocytes into the spinal cord following peripheral nerve injury has been described as a contributor to sensory hypersensitivity. We used the...
Background: A myocardial ischemia/reperfusion (IR) injury activates the transient receptor potential vanilloid 1 (TRPV1) dorsal root ganglion (DRG) neurons. The activation of TRPV1 DRG neurons triggers the spinal dorsal horn and the sympathetic prega...
Astrocytes make up the predominant cell population among glial cells in the mammalian brain, and they play a vital role in ensuring its optimal functioning. They promote neuronal health and survival and protect neurons from glutamate-induced excitoto...
Pharmacotherapy of neuropathic pain is still challenging. Our earlier work indicated an analgesic effect of dimethyl trisulfide (DMTS), which was mediated by somatostatin released from nociceptor nerve endings acting on SST4 receptors. Somatostatin r...
Hecogenin is a steroidal sapogenin largely drawn from the plants of the genus Agave, commonly known as ‘sisal’, and is one of the important precursors used by the pharmaceutical industry for the synthesis of steroid hormones. Hecogenin acetate (HA) i...
Despite the availability of several modalities of treatment, including surgery, pharmacological agents, and nerve blocks, neuropathic pain is often unresponsive and sometimes progresses to intractable chronic pain. Although exercise therapy is a cand...
Galanin is a neuropeptide expressed in a small percentage of sensory neurons of the dorsal root ganglia and the superficial lamina of the dorsal horn of the spinal cord. In this work, we systematically reviewed the literature regarding the role of ga...
Persistent pain is a prevalent symptom of Parkinson’s disease (PD), which is related to the loss of monoamines and neuroinflammation. Motor cortex stimulation (MCS) inhibits persistent pain by activating the descending analgesic pathways; however, it...
It was recently shown that coffee polyphenolic extract exerts preventive effects on central neuropathic pain development, but it is unknown whether its beneficial effects are associated with only one of its major polyphenolic compounds or if the whol...
Cocaine- and amphetamine-regulated transcript (CART) peptides are involved in several physiological and pathological processes, but their mechanism of action is unrevealed due to the lack of identified receptor(s). We provided evidence for the antihy...
Neurogenic inflammation and central sensitization play a role in chronic prostatitis/chronic pelvic pain syndrome. We explore the molecular effects of low-intensity shock wave therapy (Li-ESWT) on central sensitization in a capsaicin-induced prostati...
Neuropathic pain (NP) is a common type of chronic pain caused by a lesion or disease of the somatosensory nervous system. This condition imposes a considerable economic burden on society and patients. Daphnetin (DAP) is a natural product isolated fro...
Background: Burn scar pain is considered as neuropathic pain. The anti-inflammation and anti-neuroinflammation effects of adipose-derived stem cells (ASCs) were observed in several studies. We designed a study using a murine model involving the trans...
Activation of TRPV1, TRPA1 or TRPM8 channel expressed in the central terminal of dorsal root ganglion (DRG) neuron increases the spontaneous release of l-glutamate onto spinal dorsal horn lamina II (substantia gelatinosa; SG) neurons which play a piv...
Neuropathic pain indicates pain caused by damage to the somatosensory system and is difficult to manage and treat. A new treatment strategy urgently needs to be developed. Both autophagy and apoptosis are critical adaptive mechanisms when neurons enc...
Epigenetic mechanisms, including histone post-translational modifications (PTMs), play a critical role in regulating pain perception and the pathophysiology of burn injury. However, the epigenetic regulation and molecular mechanisms underlying burn i...
Andrographolide (Andro), the major constituent of Andrographis paniculata Nees (Acanthaceae), is was known to reduces inflammatory reaction. In the current study, the ability of Andro to reduce pain sensation in a rat post-operative wound model was e...
The endogenous antinociceptive descending pathway represents a circuitry of the supraspinal central nervous system whose task is to counteract pain. It includes the periaqueductal grey (PAG)-rostral ventromedial medulla (RVM)-dorsal horn (DH) axis, w...
Lameness in dairy cows is a worldwide prevalent disease with a negative impact on animal welfare and herd economy. Oxidative damage and antioxidant system dysfunction are common features of many CNS diseases, including chronic pain. The aim of this s...
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