Neuroscience letters
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Neuroscience letters · Mar 2008
Local application of capsaicin alleviates mechanical hyperalgesia after spinal nerve transection.
Whether modulation of C afferent fiber activities could relieve peripheral neuropathic pain was tested. After establishment of neuropathic pain induced by L5 and 6 spinal nerve transection (SNT), the sciatic nerve was treated with 2% capsaicin at the level of the midthigh. ⋯ Capsaicin treatment decreased TRPV1- and CGRP-positive neurons in L4 DRG of the treated side, but not the opposite side. These results suggest that local application of capsaicin onto the sciatic nerve can alleviate mechanical hyperalgesia, but not cold allodynia, in a peripheral neuropathic pain model and the pain alleviation may result from a decrease of TRPV1- and CGRP-positive sensory neurons of which fibers pass through the sciatic nerve.
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Neuroscience letters · Mar 2008
Enhanced activity of hippocampal BACE1 in a mouse model of postmenopausal memory deficits.
Ovarian hormone decline after menopause may influence cognitive performance and increase the risk for Alzheimer's disease (AD) in women. We have recently demonstrated that a combination of ovariectomy and chronic stress (OVX/stress) causes hippocampus-associated cognitive dysfunction in mice. In this study, we examined whether OVX/stress could affect the levels of AD-related molecules in the mouse hippocampus. ⋯ Although OVX or stress alone did not affect beta-site amyloid precursor protein (APP)-cleaving enzyme-1 (BACE1) activity, OVX/stress increased activity in hippocampal CA1 and CA3 regions, compared with other groups. In contrast, OVX/stress did not affect gamma-secretase activity, Abeta(1-40), and phosphorylated-tau levels in the hippocampus. These findings suggest that a stressful life after menopause can influence the levels of AD-related molecules and that BACE1 is the most sensitive molecule for such a situation.
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Neuroscience letters · Mar 2008
Prevention of chronic stress-induced depression-like behavior by inducible nitric oxide inhibitor.
Depression is associated with significant morbidity and functional disability, and it is thus important to reveal the mechanism of depression. A variety of studies suggest an involvement of neuronal nitric oxide synthase in the pathophysiological mechanism of none-stress-associated depression-like behavior in rodents. ⋯ Here we show that intra-hippocampal injections of the iNOS inhibitor aminoguanidine during chronic unexpected mild stress (CUMS) suppressed CUMS-induced depression-like behavioral changes, including a reduction in sucrose preference, body weight, locomotor activity, rearing and grooming in open field test, and increased duration of immobility in forced swimming test. Thus, inhibition of hippocampal iNOS may prevent the development of CUMS model of depression.
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Neuroscience letters · Mar 2008
Repeated administration of mirtazapine inhibits development of hyperalgesia/allodynia and activation of NF-kappaB in a rat model of neuropathic pain.
Antidepressants have been widely used to treat neuropathic pain for many years. However, the mechanisms of their analgesic actions are little known and remain controvertible. Recent studies indicate that cytokines in central nervous system (CNS) play a critical role in the pathological states of pain. ⋯ We found that mirtazapine (20 and 30 mg/kg) can markedly attenuate mechanical and thermal hyperalgesia produced by nerve transection, most significantly on the 14th day. The elevated TNFalpha, IL-1beta and NF-kappaB in brain were accordingly reduced, while the expression of increased IL-10 were even stimulated after repeated mirtazapine administration. Our data could conclude that mirtazapine suppressed neuropathic pain partially through inhibiting cerebral proinflammatory cytokines production and NF-kappaB activation in CNS.
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Neuroscience letters · Mar 2008
Implication of endogenous beta-endorphin in the inhibition of the morphine-induced rewarding effect by the direct activation of spinal protein kinase C in mice.
It has often been proposed that opioid addiction does not arise as a consequence of opioid treatment for pain. Recently, we demonstrated that activated protein kinase C (PKC) in the spinal cord associated with chronic pain-like hyperalgesia suppressed the morphine-induced rewarding effect in mice. In the present study, we investigated whether a gene deletion for an endogenous mu-opioid peptide beta-endorphin could affect pain-like behavior and the suppression of the morphine-induced rewarding effect by the direct activation of PKC in the spinal cord. ⋯ This suppression of morphine reward was eliminated in mice that lacked beta-endorphin. In contrast, thermal hyperalgesia and pain-like behaviors were not affected in beta-endorphin knockout mice. These results suggest that the activation of PKC in the spinal cord may play an essential role in the suppression of the morphine-induced rewarding effect in mice with neuropathic pain through the constant release of beta-endorphin.