Brain research
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Recent studies indicate that reactive oxygen species (ROS) are involved in persistent pain, including neuropathic and inflammatory pain. Edaravone, a free radical scavenger, which is widely used clinically in Japan for acute cerebral infarction to prevent ischemia reperfusion injury, has been shown to inhibit inflammatory-induced pain in rats. However, it is unknown whether edaravone is effective on neuropathic pain. ⋯ Furthermore, we found that preemptive edaravone treatment can reduce the SNL-induced pJNK expression in the ipsilateral DRG. Taken together, the present study indicated that edaravone could prevent the development of SNL-induced neuropathic pain but had little effects on the established neuropathic pain. The inhibition of the signaling pathway of JNK cascade or suppression of the possible ROS-induced hyper-excitability of DRG neurons might be, at least in part, mechanisms underlying the effects of edaravone on SNL-induced neuropathic pain.
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Transient receptor potential vanilloid 1 (TRPV1) receptors are critical to nociceptive processing. Understanding how these receptors are modulated gives insight to potential therapies for pain. We demonstrate using double labeling immunohistochemistry that Group II metabotropic glutamate receptors (mGluRs) are co-expressed with TRPV1 on rat dorsal root ganglion (DRG) cells. ⋯ The data indicate that group II mGluRs and TRPV1 receptors are co-expressed on peripheral nociceptors and activation of mGluRs can inhibit painful sensory transmission following TRPV1 activation. The data are consistent with group II and TRPV1 receptors being linked intracellularly by the cAMP/PKA pathway. Peripheral group II mGluRs are important targets for drug discovery in controlling TRPV1-induced nociception.
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Perinatal development of the mammillothalamic tract and innervation of the anterior thalamic nuclei.
Axonal projections originating from the mammillary bodies represent important pathways that are essential for spatial information processing. Mammillothalamic tract is one of the main efferent projection systems of the mammillary body belonging to the limbic "Papez circuit". This study was aimed to describe the schedule of the mammillothalamic tract development in the rat using carbocyanine dye tracing. ⋯ Ipsilateral projections from the medial mammillary nucleus to the anteromedial and anteroventral thalamic nuclei develop from E20 to P6. Bilateral projections from the lateral mammillary nucleus to the anterodorsal thalamic nuclei develop later, on P3-P6, after the formation of the thalamic decussation of the mammillary body axons. Unique spatial and temporal pattern of the perinatal development of ascending mammillary body projections to the anterior thalamic nuclei may reflect the importance of these connections within the limbic circuitry.
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Recent results implicate a new original mechanism involving oxytocin (OT), as a mediator via descending fibers of the paraventricular hypothalamic nucleus (PVN), in antinociception and analgesia. In rats electrical stimulation of the PVN or topical application of OT selectively inhibits A-delta and C fiber responses in superficial dorsal horn neurons, and this inhibition is reversed by a selective OT antagonist. However, little is known about the mechanisms and the spinal elements participating in this phenomenon. ⋯ Moreover, the topical administration of naloxone or a mu-opiate receptor antagonist beta-funaltrexamine only partially blocks the inhibitory effects produced by OT application or PVN electrical stimulation. Thus, this OT mechanism only involves opiate participation to a minor extent. The OT-specific, endogenous descending pathway represents an interesting mechanism to resolve chronic pain problems in special the neuropathic pain.
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EUK-207 is a synthetic superoxide dismutase/catalase mimetic that has been shown to reverse age-related learning deficits and brain oxidative stress in mice. In the present experiments, we tested the effects of EUK-207 on oxygen/glucose deprivation (OGD)-induced cell death in cultured hippocampal slices and on several mechanisms that have been postulated to participate in this process. Cultured hippocampal slices were subjected to 1 h OGD followed by 3 or 24 h recovery in regular medium with glucose and oxygen. ⋯ In conclusion, EUK-207 provides neuroprotection against OGD-induced cell death in cultured hippocampal slices. As EUK-207 prevents free radical formation and lipid peroxidation, the neuroprotection is related to elimination of free radical generation and lipid peroxidation, as well as to decreased activation of pro-apoptotic factors. Our data support the further clinical evaluation of this class of molecules for the prevention of ischemic cell damage.