Articles: neuropathic-pain.
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Neurochemical research · May 2016
JAB1 is Involved in Neuropathic Pain by Regulating JNK and NF-κB Activation After Chronic Constriction Injury.
Neuropathic pain, caused by a lesion or dysfunction of the somatosensory nervous system, is a severe debilitating condition with which clinical treatment remains challenging. Jun activation domain-binding protein (JAB1) is a multifunctional protein that participates in several signaling pathways, controlling cell proliferation and apoptosis. However, the expression and possible function of JAB1 in the pathogenesis of neuropathic pain has not been elucidated. ⋯ In addition, we showed that CCI induced phosphorylation of p65 and JNK in vivo. Intrathecal injection of JAB1 siRNA significantly attenuated the CCI-induced JNK and p65 phosphorylation and alleviated both mechanical allodynia and heat hyperalgesia in rats. Taken together, these results suggested that JAB1 promotes neuropathic pain via positively regulating JNK and NF-κB activation.
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The current study was to examine the underlying mechanisms responsible for the role of mammalian target of rapamycin (mTOR) in regulating bone cancer-evoked pain and the tolerance of systemic morphine. Breast sarcocarcinoma Walker 256 cells were implanted into the tibia bone cavity of rats and this evoked significant mechanical and thermal hyperalgesia. Our results showed that the protein expression of p-mTOR, mTOR-mediated phosphorylation of 4E-binding protein 4 (4E-BP1), p70 ribosomal S6 protein kinase 1 (S6K1) as well as phosphatidylinositide 3-kinase (p-PI3K) pathways were amplified in the superficial dorsal horn of the spinal cord of bone cancer rats compared with control rats. ⋯ Additionally, rapamycin enhanced attenuations of protein kinase Cɛ (PKCɛ)/protein kinase A (PKA) induced by morphine and further extended analgesia of morphine via µ-opioid receptor (MOR). Our data for the first time revealed specific signaling pathways leading to bone cancer pain, including the activation of mTOR and PI3K and downstream PKCɛ/PKA, and resultant sensitization of MOR. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of bone cancer pain often observed in clinics.
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Glutamate transporter-1 (GLT-1) reduction causes dysregulation of excitatory-inhibitory balance, contributing toward neuropathic pain development. However, the mechanisms underlying GLT-1 downregulation are still unclear. Histone acetylation plays a pivotal role in the regulation of gene expression. ⋯ Immunofluorescent histochemistry showed that both GLT-1 and AcH3 had high expressions in the dorsal horn. Double staining indicated that several GLT-1-positive cells were colocalized with AcH3. Our data provide evidence that histone deacetylation may contribute toward the loss of GLT-1 and this could be a new consideration for the development of more effective strategies for treating neuropathic pain.
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Neuroscience letters · Apr 2016
Mas-related gene (Mrg) C receptors inhibit mechanical allodynia and spinal microglia activation in the early phase of neuropathic pain in rats.
Mas-related gene (Mrg) C receptors are exclusively expressed in the trigeminal and dorsal root ganglia (DRG). However, their functional roles are poorly understood. This study was aimed to determine the effect of MrgC receptors on pain hypersensitivity in the early phase of neuropathic pain and its underlying mechanisms. ⋯ On the other hand, SNL, but not sham, surgery reduced the expression of MrgC receptor mRNA in the injured L5 DRG without changing thier levels in the adjacent uninjured L4 or L6 DRG on day 2 following the surgery. These results suggest that the activation of MrgC receptors can relieve pain hypersensitivity by the inhibition of nNOS increase in DRG neurons and microglia activation in the spinal dorsal horn in the early time following peripheral nerve injury. This study provides evidence that MrgC receptors could be targeted as a novel therapy for neuropathic pain with limited unwanted effects.
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Dexmedetomidine (Dex) is a novel Alpha 2-adrenoceptor agonist. It decreases sympathetic tone and attenuates the stress responses to anesthesia and surgery. People exposed to cold suffer unpleasant thermal pain, which is experienced as stress and causes the release of noradrenaline from the sympathetic terminals. ⋯ A significant decrease of serum IL-6 and TNF-α was demonstrated in CCI+RCS and CCI+Dex groups. The therapeutic effectiveness of dexmedetomidine in neuropathic pain may be through inhibition of proinflammatory cytokines, primarily IL-6 and TNF-α. Moreover, cold stress may result in increased resistance to neuropathic pain.