Mol Pain
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Effects of Fu's Subcutaneous Needling on Mitochondrial Structure and Function in Rats with Sciatica.
To observe the effects of Fu's subcutaneous needling (FSN) and acupuncture treatment on the mitochondrial structure and function of the skeletal muscle tissue of rats with sciatica. Forty Sprague-Dawley rats were divided into control, model, acupuncture, and FSN groups (10 each) according to a random number table. The control group was left untreated. ⋯ The state of mitochondria in the FSN group was close to that in the control group and was remarkably better than that in the acupuncture group. The activities of mitochondrial CS and respiratory chain complex II in the skeletal muscle of the treated rats decreased compared with the control group (p < 0.05), and their levels were better in the FSN group than in the acupuncture group (p < 0.05). FSN treatment for 1 week considerably improved the pain thresholds and improved the skeletal muscle mitochondrial ultrastructure and mitochondrial function in rats with sciatica.
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Development of chronic pain has been attributed to dysfunctional GABA signaling in the spinal cord. Direct pharmacological interventions on GABA signaling are usually not very efficient and often accompanied by side effects due to the widespread distribution of GABA receptors in CNS. Transplantation of GABAergic neuronal cells may restore the inhibitory potential in the spinal cord. ⋯ We observed beneficial effects of the grafted cells in reducing hypersensitivity in all grafted animals, especially potent in the recombinant group. The level of pain-related cytokines was reduced in the grafted animals and correlation between these pain markers and actual behavior was indicated. This study demonstrated the feasibility of recombinant cell transplantation in the management of chronic pain.
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Chronic pain increases the risk of developing anxiety, with limbic areas being likely neurological substrates. Despite high clinical relevance, little is known about the precise behavioral, hormonal, and brain neuroplastic correlates of anxiety in the context of persistent pain. Previous studies have shown that decreased nociceptive thresholds in chronic pain models are paralleled by anxiety-like behavior in rats, but there are conflicting ideas regarding its effects on the stress response and circulating corticosterone levels. ⋯ Global DNA methylation was decreased in the amygdala, with no changes in DNMT3a abundance in any of the regions examined. Persistent inflammatory pain promotes anxiety -like behaviors, HPA axis activation, and epigenetic regulation through DNA methylation in the amygdala. These findings describe a molecular mechanism that links pain and stress in a well-characterized rodent model.
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Ginsenoside Rh2 is one of the major bioactive ginsenosides in Panax ginseng. Although Rh2 is known to enhance immune cells activity for treatment of cancer, its anti-inflammatory and neuroprotective effects have yet to be determined. In this study, we investigated the effects of Rh2 on spared nerve injury (SNI)-induced neuropathic pain and elucidated the potential mechanisms. ⋯ Rh2 treatment blocked the mitogen-activated protein kinase (MAPK) signaling pathway by inhibiting of phosphorylated extracellular signal-regulated kinase expression. Finally, intrathecal injection of TLR8 agonist VTX-2337 reversed the analgesic effect of Rh2. These results indicated that Rh2 relieved SNI-induced neuropathic pain via inhibiting the miRNA-21-TLR8-MAPK signaling pathway, thus providing a potential application of Rh2 in pain therapy.
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T-type Ca2+ channels play a dual role in modulating the excitability of dorsal root ganglia neurons.
A subgroup of low-threshold dorsal root ganglia (DRG) neurons discharge action potentials (APs) with an afterdepolarizing potential (ADP). The ADP is formed by T-type Ca2+ currents. It is known that T-type Ca2+ currents contribute to neuropathic pain. ⋯ After injury, the proportion of DRG neurons with large T-type Ca2+ currents increased in parallel with the increase in the incidence of large-amplitude-ADP firing. And in addition to Cav3.2, Cav3.3 channels are also likely to contribute to low-threshold firing. The data revealed that T-type Ca2+ channels may play a dual role in modulating the injured neurons' high excitability through a cooperative process with Na+ channels, thereby contributing to neuropathic pain.