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Neuropathic pain (NeP) is a type of persistent pain initiated by diseases or injuries of the nervous system. Although the underlying pathophysiological mechanisms of NeP are poorly understood, the immune system plays a key role in this condition. M2 macrophages have a key role in tissue healing and the reduction of inflammation. This systematic study aims to provide an overview of the role and importance of M2 macrophages in NeP after spinal cord injury (SCI). A comprehensive systematic review was conducted utilizing Scopus, PubMed, Embase, and ISI Web of Science databases. Two independent reviewers conducted the article selection. All publications examine the impact of M2 macrophages on NeP following spinal cord injuries. A quality assessment was conducted on bias entities that had been predetermined. Eleven papers met the criteria. According to the findings, focusing on immune cell polarization presents viable therapeutic options for treating NeP and enhancing recovery after SCI. M2 macrophages are essential for reducing neuropathic pain and promoting recovery after spinal cord injury. The modulation of M2 macrophages by a number of therapeutic approaches, including ivermectin-functionalized MWCNTs, isorhamnetin, Neuregulin-1 administration, TMEM16F inhibition, lentivirus-mediated delivery of anti-inflammatory cytokines, epigallocatechin-3-gallate, and red-light therapy promotes neuroregeneration, decreases neuroinflammatory cytokines, and reduces NeP. The results of these preclinical investigations must, however, be interpreted with caution, according to the quality assessment and risk of bias analysis of the studies that were included. Targeting M2 macrophages may have therapeutic benefits as they are essential for the management of NeP and recovery following spinal cord damage. [ABSTRACT FROM AUTHOR]

Neuropathic pain, a debilitating condition, remains a significant challenge due to the lack of effective therapeutic solutions. This study aimed to evaluate the potential of mesenchymal stromal cell (MSC)-derived conditioned medium in alleviating neuropathic pain induced by sciatic nerve compression injury in adult male rats. Forty Wistar rats were randomly assigned to four groups: control, nerve injury, nerve injury with intra-neural injection of conditioned medium, and nerve injury with intra-neural injection of culture medium. Following sciatic nerve compression, the respective groups received either 10 µl of conditioned medium from amniotic fluid-derived stem cells or an equal volume of control culture medium. Behavioral tests for cold allodynia, mechanical allodynia, and thermal hyperalgesia were conducted, and the spinal cord was analyzed using Western Blot and oxidative stress assays. The behavioral experiments showed a decrease in mechanical hyperalgesia and cold allodynia in the group receiving conditioned medium compared to the injury group and the control medium group. Western blot data revealed a decrease in the expression of the CCL2 protein and an increase in GAD65. Oxidative stress tests also showed increased levels of SOD and glutathione in conditioned media-treated animals compared to animals with nerve injury. The findings suggest that conditioned medium derived from amniotic fluid-derived stem cells can effectively reduce neuropathic pain, potentially through the provision of supportive factors that mitigate oxidative stress and inflammation in the spinal cord. [ABSTRACT FROM AUTHOR]

One of the best and most effective applied and tolerable approaches for cardioprotection is the regular exercise. In the situation of exercise activity and even cardiac ischemic injury, the activity of the myocardial stem cells and their recruiting factors are changed so that contribute to the adaptation and repairment of the myocardium. The aim of this study was to investigate the effect of myocardial preconditioning with HIIT on SDF-1a myocardial levels, CXCR4 receptors, and c-kit after acute myocardial infarction in male rats. Twenty male Wistar were randomly divided into 4 groups: control (C), training (T), myocardial infarction (MI), and training + myocardial infarction (T + MI). The training groups performed 2 weeks of high-intensity interval training in four sections. Protein expression of SDF-1, C-Kit, and CXCR4 receptors was measured by the western blot method in the myocardial tissue, and myocardial injury enzymes were measured in serum. The results showed that SDF-1, CXCR4 receptors, and C-Kit had a significant increase after two weeks of HIIT and myocardial infarction. Also, serum enzyme measurements showed a positive effect of exercise, so that in the myocardium injury, enzymes significantly increased in the MI group compared with the other three groups (p < 0.001), and there was a significant difference between the groups of T + MI in all of the enzymes of the myocardium injury compared to the C and T groups. Even short terms of HIIT can increase the levels of proteins SDF1-a, C-Kit, and CXCR4 receptors in order to cardioprotection against myocardial injury through the recruitment of stem cells. [ABSTRACT FROM AUTHOR]

Neuropathic pain (NP) following spinal cord injury (SCI) often lasts for a long time and causes a range of problems that reduce the quality of life. Current treatments are not generally effective; however, photobiomodulation therapy (PBMT) has made some progress in this area. Due to the novelty of this treatment, standard therapeutic protocols have not yet been agreed upon. In the present study, we compare the analgesic effect of two PBMT protocols (2 and 4 weeks of radiation). A total of thirty-two adult male Wistar rats were divided into four groups: control, SCI, 2 W PBMT, and 4 W PBMT. SCI was induced by an aneurism clip and PBMT used a 660-nm, initiated 30 min post-SCI, and continued daily for 2 or 4 weeks. Functional recovery, hyperalgesia, and allodynia were measured weekly. At the end of the study, the Gad65, interleukin 1-alpha (IL1α), interleukin 10 (IL10), IL4, and purinergic receptor (P2xR and P2yR) expressions were measured. Data were analyzed by Prism6. The results showed PBM irradiation for 2 and 4 weeks had the same effects in improving hyperalgesia. In the case of allodynia and functional recovery, 4 W PBMT was more effective (p<0.01). 4 W PBMT increased the Gad65 expression (p <0.001) and reduced P2Y4R (p <0.05) compared to SCI animals. The effects of 2 and 4 W PBMT were the same for IL1α, IL10, and P2X3 receptors. 4 W PBMT was more effective in reducing the complications of SCI such as pain and disability. PBMT therapy is an effective method aimed at immune system function modulation to reduce NP and motor dysfunction. [ABSTRACT FROM AUTHOR]

Background: Memory deficit is a common cognitive comorbid in patients with neuropathic pain that need better treatment. Recent research revealed that nanocurcumin has an antinociceptive action and a protective effect against memory disorders, suggesting its possible effectiveness for the treatment of neuropathic pain and its comorbidity. Methods: Adult male albino Wistar rats (n = 32) were randomly divided into four experimental groups: CCI+ nanocurcumin, CCI + vehicle, sham + nanocurcumin, and sham + vehicle. Neuropathic pain induced by a chronic constriction injury of the sciatic nerve. Nanocurcumin or vehicle was injected intraperitoneally for 10 days. Behavioral assessment achieved to evaluate pain threshold in the von Frey test and radiant heat test, also spatial learning and memory examined by the Morris water maze (MWM) test. To explore the possible relation, IL-1β, and TNF-α levels of the hippocampus measured by enzyme-linked immunosorbent assay (ELISA). Results: Our data showed that CCI caused neuropathic pain-related behaviors and spatial learning and memory disorders in rats. Chronic treatment with nanocurcumin significantly increased pain threshold (P < 0.001; F = 27.63, F = 20.58), improved spatial memory (P < 0.01; F = 47.37), and decreased the hippocampal levels of IL-1β (P < 0.001; F = 33.57) and TNF-α (P < 0.01; F = 7.25) in CCI rats. Conclusion: Chronic nanocurcumin can ameliorate pain-related behavior, improve spatial learning and memory deficits, and is associated with the reduction of IL-1β and TNF-α levels in the hippocampus in CCI rats. Nanocurcumin may be potentially providing a therapeutic alternative for the treatment of neuropathic pain and its memory impairment comorbidity. [ABSTRACT FROM AUTHOR]

Neuropathic pain (NP) is caused by damage to the nervous system due to reactive oxygen spices (ROS) increase, antioxidants reduction, ATP production imbalance, and induction of apoptosis. In this investigation, we applied low-level laser 660 nm (photobiomodulation therapy) as a new strategy to modulate pain. In order to study the effects of photobiomodulation therapy (660 nm) on NP, chronic constriction injury (CCI) model was selected. Low-level laser of 660 nm was used for 2 weeks. Thermal and mechanical hyperalgesia were measured before and after surgery on days 7 and 14, respectively. Paw withdrawal thresholds were also evaluated. Expression of p2x3, Bax, and bcl2 protein was measured by western blotting. The amount of glutathione (GSH) was measured in the spinal cord by continuous spectrophotometric rate determination method. The results are presented as mean ± SD. Statistical analysis of data was carried out using SPSS 21. CCI decreased the pain threshold, 2-week photobiomodulation therapy significantly increased mechanical and thermal threshold, decreased P2X3 expression (p < 0.001), and increased bcl2 expression (p < 0.01), but it was not effective on the Bax expression. We speculated that although photobiomodulation therapy increased ROS generation, it increased antioxidants such as GSH. Increase in bcl2 is another mitochondrial protection mechanism for cell survival and that pain relief and decrease in P2X3 expression confirm it. [ABSTRACT FROM AUTHOR]

The adipocytokine apelin is a peptide that was isolated from a bovine stomach for the first time. This peptide and its receptor are abundantly expressed in the nervous and cardiovascular systems. According to previous studies, apelin-13 protects cardiomyocytes from ischemic injury as well as apoptosis. In addition, this peptide has a neuroprotective effect on hippocampal and cultured mouse cortical neurons against NMDA receptor-mediated excitotoxicity. The present study was conducted to determine whether apelin-13 provides protection in transient focal cerebral ischemia. Focal ischemia was induced by 60-min middle cerebral artery occlusion (MCAO), followed by 23-h reperfusion. Saline as a vehicle and apelin-13 at doses of 25, 50, and 100 μg were injected intracerebroventriculary (ICV) at the beginning of ischemia. Infarct volume ,brain edema, motor dysfunction, and apoptosis were assessed 24 h after MCAO. Treatment with apelin-13 at doses of 50 and 100 μg ICV markedly reduced total infarct volumes by 45 and 55 %, respectively ( P < 0.001), but injection of apelin at lower dose (25 μg) did not change infarct volume significantly ( P > 0.05). In addition, apelin-13 at doses of 50 and 100 μg reduced brain edema ( P < 0.001) and inhibited apoptosis by decreasing caspase-3 activation ( P < 0.001). Apelin-13 did not significantly change neurological dysfunction ( P > 0.05). [ABSTRACT FROM AUTHOR]

Purpose: Ascorbic acid (AA) diminishes superoxide and thereby prevents peroxynitrite formation from superoxide and nitric oxide (NO). As the neuropathic pain could be a consequence of a defect in antioxidant defenses and changes in reactive nitrogen species, the present study was designed to investigate the involvement of NO pathway in the analgesic effect of ascorbate in the chronic constriction injury (CCI) of the sciatic nerve model in rats. Methods: Neuropathic pain induced by CCI of sciatic nerve. Sixty-four adult male rats were randomly set aside to experimental groups (control, vehicle, and treatment received AA, treatment received AA and l-arginine or l-NAME). Ascorbic acid (1, 5 mg/kg) or saline injected intraperitoneally 2 weeks after CCI. Paw withdrawal threshold and response rate were assessed by a radiant heat and acetone spray test 30 and 60 min after injection. To investigate the possible implication of NO on the analgesic effect of 5 mg/kg of AA on the second week after CCI, 60 min after injection of saline or AA, animals received an intraperitoneal injection of l-arginine (500 mg/kg), or l-NAME (20 mg/kg) and behavioral tests achieved 20 min after on. Blood samples were collected from animal groups 2 weeks after the onset of treatment for evaluation of the activities of antioxidant defense system factors such as superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione (GSH), and catalase. At the same time, lipid hydroperoxide (LPO) as a prooxidant marker, and ascorbic acid concentration also determined in plasma. Results: Single injection of 5 mg/kg but not 1 mg/kg of AA decreased pain symptoms in the second week after CCI (P < 0.001, F = 3, F = 3.2). Injection of 5 mg/kg AA alleviated the nociceptive effect of l-arginine and enhanced the analgesic effect of l-NAME and pain threshold was significantly altered in these two groups comparing the animals which received normal saline instead of AA (P < 0.001, P < 0.05, F = 2, F = 1.8, respectively). Ascorbic acid treatment (5 mg/kg) significantly improved oxidative damage as according to the decrease in the lipid peroxidation level (P < 0.01, F = 5), increasing in glutathione, glutathione peroxidase, and superoxide dismutase levels (P < 0.001, F = 11.25, F = 12.52, F = 5.65) and rising in catalase activity (P < 0.001, F = 4.7) and ascorbic acid (P < 0.001, F = 4.5) in plasma as compared with normal saline-treated rats. Conclusions: Data of this study implied the implication of nitric oxide pathway in defending effect of ascorbic acid against CCI-induced behavioral and biochemical changes in rats. [ABSTRACT FROM AUTHOR]