Neuropathic pain rats

The spinal cord microglia play a pivotal role in neuroinflammation and neuropathic pain (NP). Sodium tanshinone IIA sulfonate (STS), a derivative of tanshinone IIA, has anti-inflammatory and anti-hyperalgesic effects. However, its underlying mechanism in NP remains unclear. This study aimed to investigate the effect of STS and elucidate possible mechanisms in a rat model of spared nerve injury. In vivo experiments, STS and AG490 were administered intraperitoneally once daily for 14 consecutive days after surgery...

Refractory peripheral neuropathy can occur as a side effect in 60-70% of patients receiving Paclitaxel (PTX). Yokukansan (YKS) is a Japanese herbal medicine reported to have analgesic properties for entrapment nerve injuries. Therefore, we investigated the anti-allodynic effect of Yokukansan on Paclitaxel-induced neuropathic pain. All experiments used 6-week-old male Sprague Dawley rats. Mechanical allodynia was evaluated using a dynamic plantar aesthesiometer. A mobile touch-stimulator unit applied progressively increasing force to the mid-plantar region of the hind paw in a vertical direction until the animal withdrew its paw...

BACKGROUND: Pannexin1 (Panx1) is a membrane channel expressed in different cells of the nervous system and is involved in several pathological conditions, including pain and inflammation. At the central nervous system, the role of Panx1 is already well-established. However, in the periphery, there is a lack of information regarding the participation of Panx1 in neuronal sensitization. The dorsal root ganglion (DRG) is a critical structure for pain processing and modulation. For this reason, understanding the molecular mechanism in the DRG associated with neuronal hypersensitivity has become highly relevant to discovering new possibilities for pain treatment...

EC5026 is a novel soluble epoxide hydrolase inhibitor being developed clinically to treat neuropathic pain and inflammation. In the current study, we employed the LC-ESI-Q-TOF-MS/MS technique to identify four in-vivo phase-I metabolites of EC5026 in rat model, out of which three were found to be novel. The identified metabolites include aliphatic hydroxylation, di-hydroxylation, terminal desaturation, and carboxylation. No phase-II metabolites were found. The pharmacokinetic profile of identified metabolites was established after a single oral dose of EC5026 to Wistar rats...

Chronic postsurgical pain (CPSP) with high incidence negatively impacts the quality of life. X-C motif chemokine 13 (CXCL13) has been associated with postsurgery inflammation and exacerbates neuropathic pain in patients with CPSP. This study was aimed to illustrate the relationship between CXCL13 and nod-like receptor protein-3 (NLRP3), which is also involved in CPSP. A CPSP model was constructed by skin/muscle incision and retraction (SMIR) in right medial thigh, and the rats were divided into three groups: Sham, SMIR, and SMIR + anti-CXCL13 (intrathecally injected with anti-CXCL13 antibody)...

Preclinical studies indicate that diverse muscarinic receptor antagonists, acting via the M1 sub-type, promote neuritogenesis from sensory neurons in vitro and prevent and/or reverse both structural and functional indices of neuropathy in rodent models of diabetes. We sought to translate this as a potential therapeutic approach against structural and functional indices of diabetic neuropathy using oxybutynin, a muscarinic antagonist approved for clinical use against overactive bladder. Studies were performed using sensory neurons maintained in vitro, rodent models of type 1 or type 2 diabetes and human subjects with type 2 diabetes and confirmed neuropathy...

Animal models remain necessary tools to study neuropathic pain. This manuscript describes the distal infraorbital nerve chronic constriction injury (DIoN-CCI) model to study trigeminal neuropathic pain in mice. This includes the surgical procedures to perform the chronic constriction injury and the postoperative behavioral tests to evaluate the changes in spontaneous and evoked behavior that are signs of ongoing pain and mechanical allodynia. The methods and behavioral readouts are similar to the infraorbital nerve chronic constriction injury (IoN-CCI) model in rats...

A large proportion of patients with chronic pain experience co-morbid anxiety. The medial prefrontal cortex (mPFC) is proposed to underlie this comorbidity, but the molecular and neuronal mechanisms are not fully understood. Here, we reported that impaired neuronal macroautophagy in the prelimbic cortical (PrL) subregion of the mPFC paralleled the occurrence of anxiety-like behaviors in rats with chronic spared nerve injury (SNI). Intriguingly, such macroautophagy impairment was mainly observed in a FOS/c-Fos+ neuronal subpopulation in the PrL...

Bestrophin-1, a calcium-activated chloride channel (CaCC), is involved in neuropathic pain; however, it is unclear whether it has a dimorphic role in female and male neuropathic rats. This study investigated if 17β-estradiol and estrogen receptor alpha (ERα) activation regulate bestrophin-1 activity and expression in neuropathic rats. Neuropathic pain was induced by L5-spinal nerve transection (SNT). Intrathecal administration of CaCCinh-A01 (0.1-1 µg), a CaCC blocker, reversed tactile allodynia induced by SNT in female but not male rats...

Tinnitus is known to affect 10-15 % of the population, severely impacting 1-2 % of those afflicted. Canonically, tinnitus is generally a consequence of peripheral auditory damage resulting in maladaptive plastic changes in excitatory/inhibitory homeostasis at multiple levels of the central auditory pathway as well as changes in diverse nonauditory structures. Animal studies of primary auditory cortex (A1) generally find tinnitus-related changes in excitability across A1 layers and differences between inhibitory neuronal subtypes...

Growing evidence supports the analgesic efficacy of electroacupuncture (EA) in managing chronic neuropathic pain (NP) in both patients and NP models induced by peripheral nerve injury. However, the underlying mechanisms remain incompletely understood. Ferroptosis, a novel form of programmed cell death, has been found to be activated during NP development, while EA has shown potential in promoting neurological recovery following acute cerebral injury by targeting ferroptosis. In this study, to investigate the detailed mechanism underlying EA intervention on NP, male Sprague-Dawley rats with chronic constriction injury (CCI)-induced NP model received EA treatment at acupoints ST36 and GV20 for 14 days...

BACKGROUND: Neuropathic pain (NP) is a highly challenging condition with complex pathological mechanisms, and the spinal gamma aminobutyric acid A receptor receptor plays a crucial role in its progression. Recent studies have revealed a potential interaction between neuroplastin 65 (NP65) and gamma aminobutyric acid A receptor α2 subunit (GABAAR-α2) on the cell surface. We hypothesize that NP65 is involved in the pathogenesis of NP by regulating the level of GABAAR-α2...

OBJECTIVE: To determine the effective dose and therapeutic potential of maropitant using through expression of mediators of oxidative stress, inflammatory and of the unfolded protein response (UPR) (bio) markers on spinal cord using a model of neuropathic pain induced through chronic constriction injury (CCI) in rats. STUDY DESIGN: Randomized, blinded, prospective experimental study. ANIMALS: 98 male Wistar rats. METHODS: Rats were anesthetized with sevoflurane and after CCI, they were randomly assigned to the following groups that received: vehicle, 3, 6, 15, 30 e 50 mg/kg/24q of maropitant...

Trigeminal neuropathic pain is emotionally distressing and disabling. It presents with allodynia, hyperalgesia and dysaesthesia. In preclinical models it has been assumed that cephalic nerve constriction injury shows identical molecular, cellular, and sex dependent neuroimmune changes as observed in extra-cephalic injury models. This study sought empirical evidence for such assumptions using the infraorbital nerve chronic constriction model (ION-CCI). We compared the behavioural consequences of nerve constriction with: (i) the temporal patterns of recruitment of macrophages and T-lymphocytes at the site of nerve injury and in the trigeminal ganglion; and (ii) the degree of demyelination and axonal reorganisation in the injured nerve...

AIM: To explore the post-translational regulation of TRPV1, which plays an important role in neuropathic low back pain (NLBP). MATERIAL AND METHODS: qPCR was used to examine the gene mRNA levels. Western blot was used to examine the protein level. NLBP rat model was established for confirming what we observed in clinical samples. Dual-luciferase assay was used to verify the miR-199 targets on the 3'UTR of TRPV1. Cell coculture was used to explore the interaction between macrophages and nerve cells...

The glymphatic system plays a crucial role in maintaining optimal central nervous system (CNS) function by facilitating the removal of metabolic wastes. Aquaporin-4 (AQP4) protein, predominantly located on astrocyte end-feet, is a key pathway for metabolic waste excretion. β-Dystroglycan (β-DG) can anchor AQP4 protein to the end-feet membrane of astrocytes and can be cleaved by matrix metalloproteinase (MMP)-9 protein. Studies have demonstrated that hyperglycemia upregulates MMP-9 expression in the nervous system, leading to neuropathic pain...

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Experimental autoimmune neuritis is a common animal model for acute human immune-mediated polyneuropathies. Although already established in 1955, a number of pathophysiological mechanisms remain unknown. In this study, we extensively characterize experimental autoimmune neuritis progression in Lewis rats, including new insights into the integrity of small nerve fibres, neuropathic pain and macrophage activation. Acute experimental autoimmune neuritis was induced with P253-78 peptide and consequently investigated using the gait analysis system CatWalk XT, electrophysiological and histopathological analyses, quantitative polymerase chain reaction (PCR), dorsal root ganglia outgrowth studies, as well as the von Frey hair and Hargreaves tests...

This study aimed to elucidate the mechanism of Wenzheng Jiedu Powder Modified Formula (WJPMF) in treating neuropathic pain (NP). Network pharmacology and experimental verification were integrated to explore the therapeutic effects and key targets of WJPMF. Active components, corresponding target genes, and absorption, distribution, metabolism, and excretion (ADME) genes of WJPMF against NP were screened from public databases. Network analysis and molecular docking were conducted to identify key targets and verify binding abilities...

Previously, we found that serotonin (5-HT) release in the central nucleus of the amygdala (CeA) of anesthetized rats decreases in response to innocuous stroking of the skin, irrespective of stimulus laterality, but increases in response to noxious pinching applied to a hindlimb contralateral to the 5-HT measurement site. The aim of the present study was to determine whether intra-CeA 5-HT release responses to cutaneous stimulation were altered in an animal model of neuropathic pain induced by ligation of the left L5 spinal nerve...