The Journal of neuroscience : the official journal of the Society for Neuroscience
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There is compelling evidence that oligodendrocyte apoptosis, in response to CNS inflammation, contributes significantly to the development of the demyelinating disorder multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Therefore, approaches designed to protect oligodendrocytes would likely have therapeutic value. Activation of pancreatic endoplasmic reticulum kinase (PERK) signaling in response to endoplasmic reticulum (ER) stress increases cell survival under various cytotoxic conditions. ⋯ Importantly, we found that enhanced activation of PERK signaling specifically in oligodendrocytes significantly attenuated EAE disease severity, which was associated with reduced oligodendrocyte apoptosis, demyelination, and axonal degeneration. This effect was not the result of an altered degree of the inflammatory response in EAE mice. Our results provide direct evidence that activation of PERK signaling in oligodendrocytes is cytoprotective, protecting mice against EAE.
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Intrathecal application of morphine is among the most powerful methods used to treat severe chronic pain. However, this approach commonly produces itch sufficiently severe that patients are forced to choose between relief of pain or itch. The neuronal populations responsible for processing and transmitting information underlying itch caused by intrathecal application of morphine have not been identified and characterized. ⋯ In addition, intrathecal application of morphine increased responses to pruritogens injected into the skin and greatly heightened responses to innocuous mechanical stimuli. In contrast, the ongoing activity and responses to noxious pinches in nociceptive VTT neurons were frequently inhibited by the same dose of morphine. These results reveal that i.t. application of morphine affects specific subpopulations of VTT neurons in ways that may produce itch, hyperknesis, alloknesis, and analgesia.