Articles: neuralgia.
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The proteasome inhibitor bortezomib (BTZ) is a potent first-line anticancer drug for multiple myeloma; nonetheless, it induced peripheral neuropathy. It has been suggested that many cytokines may play a role in mediating neuropathic pain, but the underlying molecular mechanism is not fully understood. Recent studies have shown that neuropathic pain is closely related to the purinergic ligand-gated ion channel 7 receptor (P2X7R), one of the P2X receptors, which is richly expressed in glial cells. ⋯ Inhibiting p38MAPK phosphorylation with SB203580 resulted in downregulation of P2X7R expression levels. Inhibition of P2X7R with Brilliant Blue G (BBG) reversed neuropathic pain might decrease through the expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 via inhibiting p38MAPK phosphorylation. The P2X7R/p38MAPK signaling pathway in SGCs of DRG and microglia of SDH might be a potential pharmacological target behind this mechanism as an opportunity to relieve BTZ-induced neuropathic pain.
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Physical exercise has been established as a low-cost, safe, and effective way to manage chronic pain, but exact mechanisms underlying such exercise-induced hypoalgesia (EIH) are not fully understood. Since a growing body of evidence implicated the amygdala (Amyg) as a critical node in emotional affective aspects of chronic pain, we hypothesized that the Amyg may play important roles to produce EIH effects. Here, using partial sciatic nerve ligation (PSL) model mice, we investigated the effects of voluntary running (VR) on the basal amygdala (BA) and the central nuclei of amygdala (CeA). ⋯ In addition, a tracer experiment demonstrated a marked increase in activated Glu neurons in the medBA projecting into the nucleus accumbens lateral shell in runner mice. Thus, our results suggest that VR may not only produce suppression of the negative emotion such as fear and anxiety closely related with pain chronification, but also promote pleasant emotion and hypoalgesia. Therefore, we conclude that EIH effects may be produced, at least in part, via such plastic changes in the Amyg.
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Mounting evidence has shown that sirtuin 1 (SIRT1), a class III histone deacetylase, alleviated several types of neuropathic pain in the spinal cord and dorsal root ganglion and regulated some aberrant behaviors in the ventral tegmental area (VTA) and the nucleus accumbens (NAc). ⋯ The discovery of the effect of SIRT1 on neuropathic pain in the VTA represents an important step forward in understanding the analgesic mechanisms of the VTA-NAc pathway.
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Journal of neurosurgery · Jan 2020
Neurochemical effects of motor cortex stimulation in the periaqueductal gray during neuropathic pain.
Motor cortex stimulation (MCS) is a neurosurgical technique used to treat patients with refractory neuropathic pain syndromes. MCS activates the periaqueductal gray (PAG) matter, which is one of the major centers of the descending pain inhibitory system. However, the neurochemical mechanisms in the PAG that underlie the analgesic effect of MCS have not yet been described. The main goal of this study was to investigate the neurochemical mechanisms involved in the analgesic effect induced by MCS in neuropathic pain. Specifically, we investigated the release of γ-aminobutyric acid (GABA), glycine, and glutamate in the PAG and performed pharmacological antagonism experiments to validate of our findings. ⋯ These results suggest that the neurotransmitters glycine and GABA released in the PAG may be involved in the analgesia induced by cortical stimulation in animals with neuropathic pain. Further investigation of the mechanisms involved in MCS-induced analgesia may contribute to clinical improvements for the treatment of persistent neuropathic pain syndromes.