Articles: neuropathic-pain.
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We have demonstrated that electroacupuncture (EA) of "Weizhong" (BL 40) and "Huantiao" (GB 30) could evidently relieve mechanical hyperalgesia in spared nerve injury (SNI) rats. The present study was designed to observe the effect of EA on levels of cAMP, and protein kinase A (PKA) and cAMP response element binding protein (CREB) in the lumbar spinal cord of the same pain model rats, so as to explore its mechanisms underlying improvement of neuropathic pain. ⋯ EA intervention-induced down-regulation of cAMP, PKA and CREB levels in the lumbar spinal cord may contribute to its analgesic effect in neuropathic pain rats, suggesting an involvement of reduction of cAMP/PKA/CREB signaling of spinal cord in EA analgesia.
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Neuropathic pain is associated with gene expression changes within the dorsal root ganglion (DRG) after peripheral nerve injury, which involves epigenetic mechanisms. Coactivator-associated arginine methyltransferase 1 (CARM1), an epigenetic activator, regulates gene transcriptional activity by protein posttranslational modifications. ⋯ Furthermore, pharmacological inhibition of CARM1 mitigated peripheral nerve injury-induced mechanical allodynia and thermal hyperalgesia. Given that CARM1 inhibition or knockdown attenuated the induction and maintenance of neuropathic pain after peripheral nerve injury, our findings suggest that CARM1 may serve as a promising therapeutic target for neuropathic pain treatment in clinical applications.
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Acta neurochirurgica · Dec 2018
Spinal cord stimulation modulates descending pain inhibition and temporal summation of pricking pain in patients with neuropathic pain.
Spinal cord stimulation (SCS) is an established treatment option for patients with refractory chronic pain conditions. While effects of SCS on dorsal horn neuronal circuitries are intensively studied, current knowledge on the impact of SCS on descending pain pathways is scarce and relies on preclinical data. We aimed to address this topic and hypothesized a significant effect of SCS on descending pain modulation. In light of current efforts to determine the sensitivity of "static" versus "dynamic" somatosensory parameters to characterize pathophysiological pain conditions, all SCS patients were carefully investigated using both classes of somatosensory outcome parameters. ⋯ Our study provides first human evidence for an impact of SCS on descending pain pathways in the dorsolateral funiculus and emphasizes the significance of "dynamic" pain measures like "CPM"-efficacy and "temporal summation" to evaluate SCS treatment effects. Future prospective studies may use these measures of nociceptive processing to predict SCS therapy response.
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Descending brainstem control of spinal nociceptive processing permits a dynamic and adaptive modulation of ascending sensory information. Chronic pain states are frequently associated with enhanced descending excitatory drive mediated predominantly through serotonergic neurones in the rostral ventromedial medulla. In this study, we examine the roles of spinal 5-HT2A and 5-HT3 receptors in modulating ascending sensory output in normal and neuropathic states. ⋯ The inhibitory profiles of both drugs were altered in SNL rats; ondansetron additionally inhibited neuronal responses to lower intensity punctate mechanical stimuli and noxious heat evoked responses, whereas ketanserin inhibited innocuous and noxious evaporative cooling evoked responses. Neither drug had any effect on dynamic brush evoked responses nor on spontaneous firing rates in both sham and SNL rats. These data identify novel modality and intensity selective facilitatory roles of spinal 5-HT2A and 5-HT3 receptors on sensory neuronal processing within the spinothalamic-somatosensory cortical pathway.