Articles: neuropathic-pain.
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Pancreatitis-associated proteins (PAPs) display multiple functions in visceral diseases. Previous studies showed that the expression level of PAP-I was low in the DRG of naive rats but was de novo expressed after peripheral nerve injury. However, its role in neuropathic pain remains unknown. ⋯ Here we reveal that, after peripheral nerve injury, PAP-I can be transported to the spinal dorsal horn and is crucial in the progression of neuropathic pain. Importantly, we prove that PAP-I mainly functions through activating the spinal microglia via the CCR2-p38 MAPK pathway. Furthermore, we confirm that the proinflammatory effect of PAP-I is more prominent after the establishment of neuropathic pain, thus indicating that microglia also participate in the maintenance phase of neuropathic pain.
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Background and Objectives: Currently, few studies have reported the effects of opioids during continuous epidural infusion (CEI) to control pain owing to herpes zoster (HZ). This study aimed to retrospectively compare the effectiveness of epidural opioids in the treatment of acute HZ pain. Materials and Methods: We reviewed medical records of 105 patients who were divided into two groups: R group (CEI with ropivacaine) and RF group (CEI with ropivacaine and fentanyl). ⋯ However, the difference was not statistically significant. Conclusions: No difference was observed in the management of HZ pain and the prevention of postherpetic neuralgia between the two groups. The incidence of complications tended to be higher in the RF group than in the R group.
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Voltage-gated T-type Ca2+ (CaV3) channels regulate diverse physiological events, including neuronal excitability, and have been linked to several pathological conditions such as absence epilepsy, cardiovascular diseases, and neuropathic pain. It is also acknowledged that calcium/calmodulin-dependent protein kinase II and protein kinases A and C regulate the activity of T-type channels. Interestingly, peripheral nerve injury induces tactile allodynia and upregulates CaV3.2 channels and cyclin-dependent kinase 5 (Cdk5) in dorsal root ganglia (DRG) and spinal dorsal horn. ⋯ The present work shows that the exacerbated expression of Cdk5 in a preclinical model of neuropathic pain increases the functional expression of CaV3.2 channels. This finding is relevant for the understanding of the molecular pathophysiology of the disease. Additionally, this work may have a substantial translational impact, since it describes a novel molecular pathway that could represent an interesting therapeutic alternative for neuropathic pain.
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Frontiers in pharmacology · Jan 2020
ReviewDrug Repositioning for the Prevention and Treatment of Chemotherapy-Induced Peripheral Neuropathy: A Mechanism- and Screening-Based Strategy.
Chemotherapy-induced peripheral neuropathy (CIPN) is a severe adverse effect observed in most patients treated with neurotoxic anti-cancer drugs. Currently, there are no therapeutic options available for the prevention of CIPN. Furthermore, few drugs are recommended for the treatment of existing neuropathies because the mechanisms of CIPN remain unclear. ⋯ Cancer chemotherapy is performed in a planned manner; therefore, preventive strategies can be planned for CIPN. Drug repositioning studies, which identify the unexpected actions of already approved drugs, have increased in recent years. We have also focused on drug repositioning studies, especially for prevention, because they should be rapidly translated to patients suffering from CIPN.
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Antimicrotubulin chemotherapeutic agents, including plant-derived vincaalkaloids such as vincristine, can cause peripheral neuropathic pain. Exogenously activated heme oxygenase 1 (HO-1) is a potential therapy for chemotherapy-induced neuroinflammation. In this study, we investigated a role for Nrf2/HO-1/CO in mediating vincristine-induced neuroinflammation by inhibiting connexin 43 (Cx43) production in the spinal cord following the intrathecal application of the HO-1 inducer protoporphyrin IX cobalt chloride (CoPP) or inhibitor protoporphyrin IX zinc (ZnPP), and we analyzed the underlying mechanisms by which levo-corydalmine (l-CDL, a tetrahydroprotoberberine) attenuates vincristine-induced pain. ⋯ Furthermore, l-CDL had no effect on Cx43 following the silencing of the HO-1 gene. Taken together, our findings reveal a novel mechanism by which Nrf2/HO-1/CO mediates Cx43 expression in vincristine-induced neuropathic pain. In addition, the present findings suggest that l-CDL likely protects against nerve damage and attenuates vincristine-induced neuroinflammation by upregulating Nrf2/HO-1/CO to inhibit Cx43 expression.