Brain research
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Secondary brain damage plays a critical role in the outcome of patients with traumatic brain injury (TBI). The multiple mechanisms underlying secondary brain damage, including posttraumatic cerebral ischemia, glutamate excitotoxicity, oxidative stress, calcium overload and inflammation, are associated with increased mortality and morbidity after head injury. TBI is documented to have detrimental effects on mitochondria, such as alterations in glucose utilization and the depression of mitochondrial oxidative phosphorylation. ⋯ The differences may indicate the degree of metabolic and physiologic dysfunction. Our results will better define the roles of gene expression and metabolic function in long-term prognosis and outcome after TBI. With a considerable understanding of post-injury mitochondrial dysfunction, therapeutic interventions targeted to the mitochondria may prevent secondary brain damage that leads to long-term cell death and neurobehavioral disability.
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A subset of German function verbs can be used either in a full, concrete, 'heavy' ("take a computer") or in a more metaphorical, abstract or 'light' meaning ("take a shower", no actual 'taking' involved). The present magnetoencephalographic (MEG) study explored whether this subset of 'light' verbs is represented in distinct cortical processes. A random sequence of German 'heavy', 'light', and pseudo verbs was visually presented in three runs to 22 native German speakers, who performed lexical decision task on real versus pseudo verbs. ⋯ Thus, 'heavy' versus 'light readings' of verbs already modulate early posterior visual evoked response even when verbs are presented in isolation. This response becomes clearer in the disambiguating contextual condition. This type of study shows for the first time that language processing is sensitive to representational differences between two readings of one and the same verb stem.
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Tolerance to peripheral antinociception after chronic exposure to systemic morphine was assessed in mice with chronic CFA-inflammation; cross-tolerance to locally administered mu, delta and kappa-opioid agonists and levels of beta-arrestins in the injured paw, were also evaluated. Tolerance was induced by the subcutaneous implantation of a 75 mg morphine-pellet, and antinociception evaluated with the Randall-Selitto test, 5 min after the subplantar injection of morphine, fentanyl, buprenorphine, DPDPE, U-50488H or CRF. Experiments were performed in the absence and presence of CFA-inflammation, in animals implanted with a morphine or placebo pellet. ⋯ Tolerance did not alter beta-arrestins, but partially prevented the increase induced by inflammation. The results suggest that peripheral beta-arrestins could facilitate peripheral OR-desensitization and tolerance development. Clinically, the experiments could be useful to establish the effectiveness of local opioid administration in patients with musculoskeletal pain, chronically receiving morphine analgesia.
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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.