Neuroscience letters
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Neuroscience letters · Jan 2015
Antiallodynic effect through spinal endothelin-B receptor antagonism in rat models of complex regional pain syndrome.
Complex regional pain syndrome (CRPS) is a very complicated chronic pain disorder that has been classified into two types (I and II). Endothelin (ET) receptors are involved in pain conditions at the spinal level. We investigated the role of spinal ET receptors in CRPS. ⋯ Intrathecal BQ 788 decreased the spinal ET-1 level. These results suggest that ET-1 is involved in the development of mechanical allodynia in CRPS. Furthermore, the ET-B receptor appears to be involved in spinal cord-related CRPS.
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Neuroscience letters · Jan 2015
Reduced brain edema and infarct volume in aquaporin-4 deficient mice after transient focal cerebral ischemia.
Aquaporin-4 (AQP4) is a water channel expressed in astrocyte end-feet lining the blood-brain barrier. AQP4 deletion in mice is associated with improved outcomes in global cerebral ischemia produced by transient carotid artery occlusion, and focal cerebral ischemia produced by permanent middle cerebral artery occlusion (MCAO). ⋯ Diffusion-weighted magnetic resonance imaging showed greatest reduction in apparent diffusion coefficient around the occlusion site after reperfusion, with remarkably lesser reduction in AQP4(-/-) mice. The reduced infarct volume in AQP4(-/-) mice following transient MCAO supports the potential utility of therapeutic AQP4 inhibition in stroke.
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Neuroscience letters · Jan 2015
Suppression of network activity in dorsal horn by gabapentin permeation of TRPV1 channels: implications for drug access to cytoplasmic targets.
The effectiveness of gabapentin (GBP) in the treatment of neuropathic pain depends on access to the α2δ-1 accessory subunit of voltage-gated Ca(2+) channels. Access may be limited by its rate of entry via the neuronal system L-neutral amino acid transporter. The open pore of capsaicin-activated TRPV1 channel admits organic molecules such as local anesthetics and we calculated that GBP entry via this route would be 500× more rapid than via the transporter. ⋯ Experiments with an inhibitor of the neutral amino acid transporter, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH 300 μM), showed the actions of GBP seen in the presence of capsaicin were independent of its entry by this route. Capsaicin potentiation of GBP depression of dorsal horn activity may therefore reflect drug permeation of TRPV1 channels. Agonist activation of TRP channels may provide a means for improving drug access to cytoplasmic targets in selective neuronal populations defined on the basis of type of TRP channel expressed.
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Neuroscience letters · Jan 2015
Rosuvastatin attenuated the existing morphine tolerance in rats with L5 spinal nerve transection through inhibiting activation of astrocytes and phosphorylation of ERK42/44.
Recent studies suggested that statins have anti-inflammatory effects beyond their lipid-lowering properties. In the present study, we sought to investigate whether rosuvastatin could alleviate morphine tolerance by attenuating the glia mediated neuroinflammation in the spinal cord. Using a rat model of L5 spinal nerve transection, on day 8 after surgery morphine (10 mg/kg) was injected subcutaneously twice daily for consecutive 10 days. ⋯ Rosuvastatin administration for 5 days could restore morphine antinociceptive effect significantly. Additionally, the activation of astrocytes, the phosphorylation of extracellular signal-regulated kinase 42/44 (ERK(42/44)) and the expressions of TNFα and IL-1β were inhibited significantly by rosuvastatin. Our data suggested that rosuvastatin was a promising choice to treat neuropathic pain in combination with morphine.
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Neuroscience letters · Jan 2015
Intra-articular administration of an antibody against CSF-1 receptor reduces pain-related behaviors and inflammation in CFA-induced knee arthritis.
Several studies have shown that blockade of colony stimulating factor-1 (CSF-1) or its receptor (CSF-1R) inhibits disease progression in rodent models of rheumatoid arthritis (RA); however, the role of the CSF-1/CSF-1R pathway in RA-induced pain and functional deficits has not been studied. Thus, we examined the effect of chronic intra-articular administration of a monoclonal anti-CSF-1R antibody (AFS98) on spontaneous pain, knee edema and functional disabilities in mice with arthritis. Unilateral arthritis was produced by multiple injections of complete Freund's adjuvant (CFA) into the right knee joint of adult male ICR mice. ⋯ Intra-articular treatment with anti-CSF-1R antibody significantly increased horizontal exploratory activity and vertical rearing as well as reduced spontaneous flinching behavior and knee edema as compared to CFA-induced arthritis mice treated with PBS. Treatment with this antibody neither significantly affect mouse body weight nor the number of peripheral leukocytes. These results suggest that blockade of CSF-1R at the initial injury site (joint) could represent a therapeutic alternative for improving the functional disabilities and attenuating pain and inflammation in patients with RA.