Mol Pain
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Muscle pain is a common condition that relates to various pathologies. Muscle overuse induces muscle pain, and neutrophils are key players in pain production. Neutrophils also play a central role in chronic pain by secreting interleukin (IL)-18. ⋯ In stimulated muscles, pressure pain thresholds decreased, and neutrophil and IL-18 levels increased compared with that in non-stimulated muscles. The administration of IL-18-binding protein and Brilliant Blue G attenuated hyperalgesia caused by excessive muscle contraction. These results suggest that increased IL-18 secretion from larger numbers of neutrophils elicits mechanical hyperalgesia.
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Background Diabetic peripheral neuropathy is a common long-term complication of diabetes. Accumulating evidence suggests that vascular impairment plays important roles in the pathogenesis of diabetic peripheral neuropathy, while the mechanism remains unclear. We recently reported that transient receptor potential ankyrin 1 (TRPA1) is sensitized by hypoxia, which can contribute to cold hypersensitivity. ⋯ However, no difference was observed between wild-type and TRPA1-knockout mice in the hyposensitivity for current or mechanical stimulation or the deceased density of intraepidermal nerve fibers eight weeks after the streptozotocin administration. Conclusion These results suggest that TRPA1 sensitization during diabetic vascular impairment causes cold, but not mechanical, hypersensitivity in the early painful phase of diabetic peripheral neuropathy. However, TRPA1 may play little or no role in the progression of diabetic peripheral neuropathy.
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Transcription factors are proteins that modulate the transcriptional rate of target genes in the nucleus in response to extracellular or cytoplasmic signals. Activating transcription factors 2 (ATF2) and 3 (ATF3) respond to environmental signals and maintain cellular homeostasis. There is evidence that inflammation and nerve injury modulate ATF2 and ATF3 expression. ⋯ ATF2 immunoreactivity was found in dorsal root ganglia and spinal cord co-labeling with NeuN mainly in non-peptidergic (IB4+) but also in peptidergic (CGRP+) neurons. ATF2 was found mainly in small- and medium-sized neurons. These results suggest that ATF2, but not ATF3, is found in strategic sites related to spinal nociceptive processing and participates in the maintenance of neuropathic pain in rats.
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Resveratrol has been showed to relieve neuropathic pain through its anti-inflammatory effects on the peripheral nerve system. However, it is not clear whether resveratrol, especially when administered systemically, is effective in alleviating the peripheral neuropathy-induced imbalance between pro- and anti-inflammatory responses in the central nervous system. To test this, we used a rat neuropathic pain model resulting from chronic constriction injury of the sciatic nerve. ⋯ After 14 days of resveratrol treatment, expression of several anti-inflammatory cytokine receptors, including IL-1RA and IL-1R2, was increased in the dorsal spinal cord of rats with chronic constriction injury, and IL-4Rα was increased in dorsal spinal cord neurons. Knockdown of IL-4Rα in a neuronal cell line reversed the resveratrol-induced upregulation of IL-1RA and IL-1R2. These results indicate that resveratrol enhances IL-4 receptor-mediated anti-inflammatory responses in the spinal cord and thus might contribute to the alleviation of central sensitization following peripheral nerve injury.
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Breast cancer cells release the signalling molecule glutamate via the system xC- antiporter, which is upregulated to exchange extracellular cystine for intracellular glutamate to protect against oxidative stress. Here, we demonstrate that this antiporter is functionally influenced by the actions of the neurotrophin nerve growth factor on its cognate receptor tyrosine kinase, TrkA, and that inhibiting this complex may reduce cancer-induced bone pain via its downstream actions on xCT, the functional subunit of system xC-. ⋯ Cumulatively, these data suggest that the activation of TrkA by nerve growth factor may have functional implications on system xC--mediated cancer pain. System xC--mediated TrkA activation therefore presents a promising target for therapeutic intervention in cancer pain treatment.