Mol Pain
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It is documented that sensory transmission, including pain, is subject to endogenous inhibitory and facilitatory modulation at the dorsal horn of the spinal cord. Descending facilitation has received a lot of attention, due to its potentially important roles in chronic pain. ⋯ It also provides the neuronal basis to link emotional disorders such as anxiety, depression, and loss of hope to somatosensory pain and sufferings. In this review, I will review a brief history of the discovery of brainstem-spinal descending facilitation and explore new information and hypothesis for descending facilitation in chronic pain.
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Hyperbaric oxygen therapy is increasingly used in adjuvant therapies to treat neuropathic pain. However, the specific targets of hyperbaric oxygen treatment in neuropathic pain remain unclear. Recently, we found that hyperbaric oxygen therapy produces an antinociceptive response via the kindlin-1/wnt-10a signaling pathway in a chronic pain injury model in rats. ⋯ Our findings demonstrate that kindlin-1 is a key protein in the action of hyperbaric oxygen therapy in the treatment of neuropathic pain. Indeed, interference with kindlin-1 may be a drug target for reducing the neuroinflammatory responses of the glial population in neuropathic pain.
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Effective axon regeneration is achieved mainly by precise regulation of gene expression after peripheral nerve injury. MicroRNAs play an important role in controlling axon regeneration owe to its key epigenetic function in regulating gene expression. Here, we reveal that microRNA-9 (miR-9) may be a new suppressor of axon regeneration and FoxP1 is the functional target of miR-9. ⋯ Full rescuing effect of axon regeneration was achieved by FoxP1 up-regulation. Most importantly, we showed that miR-9-FoxP1 might be a new signaling pathway to regulate mammalian axon regrowth. Moreover, we provided the first evidence that maintaining a higher level of FoxP1 in sensory neurons by the microRNA is necessary for efficient axon regeneration.
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Nociception is maintained by genome-wide regulation of transcription in the dorsal root ganglia—spinal cord network. Hence, transcription factors constitute a promising class of targets for breakthrough pharmacological interventions to treat chronic pain. DNA decoys are oligonucleotides and specific inhibitors of transcription factor activities. A methodological series of in vivo–in vitro screening cycles was performed with decoy/transcription factor couples to identify targets capable of producing a robust and long-lasting inhibition of established chronic pain. Decoys were injected intrathecally and their efficacy was tested in the spared nerve injury and chronic constriction injury models of chronic pain in rats using repetitive von Frey testing. ⋯ These data highlight KLF6, KLF9, and KLF15 as transcription factors required for the maintenance of chronic pain and illustrate the potential therapeutic benefits of AYX2 for the treatment of chronic pain.