Articles: neuropathic-pain.
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Neuropeptide Y (NPY) modulates nociception in the spinal cord, but little is known about its mechanisms of release. We measured NPY release in situ using the internalization of its Y1 receptor in dorsal horn neurons. Y1 receptor immunoreactivity was normally localized to the cell surface, but addition of NPY to spinal cord slices increased the number of neurons with Y1 internalization in a biphasic fashion (EC50s of 1 nM and 1 μM). ⋯ Mechanical stimulation in vivo, with rub or clamp of the hindpaw, elicited robust Y1 receptor internalization in rats with spared nerve injury but not sham surgery. In summary, NPY is released from dorsal horn interneurons or primary afferent terminals by electrical stimulation and by activation of TRPV1, PKA or NMDA receptors in. Furthermore, NPY release evoked by noxious and tactile stimuli increases after peripheral nerve injury.
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Although ketamine has been known and clinically applied for a long time, questions still arise around the many possible indications in which the anesthetic and analgesic substance could be used. In particular, these questions relate to new indications in which ketamine is used in low subanesthetic doses. ⋯ Possible applications include the prevention of chronic postoperative pain as well as the treatment of neuropathic pain. With the treatment of refractory depression completely new therapeutic areas for ketamine could be established.
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We provide an updated review of the pharmacological treatment of neuropathic pain, with emphasis on the latest evidence-based recommendations. Drugs proposed as first line include tricyclic antidepressants (particularly amitriptyline), serotonin-noradrenaline reuptake inhibitors (particularly duloxetine), pregabalin and gabapentin. Second-line treatments include 5% lidocaine medicated plasters and capsaicin 8% patches, only for peripheral neuropathic pain and tramadol; whereas potent opioids and botulinum toxin A (for peripheral neuropathic pain) are considered third-line treatments. Future perspectives include the development of new drugs and a more personalised therapeutic approach, which is made possible by recent progress in the assessment and understanding of neuropathic pain.
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Antineoplastic drugs induce dramatic transcriptional changes in dorsal root ganglion (DRG) neurons, which may contribute to chemotherapy-induced neuropathic pain. K2p 1.1 controls neuronal excitability by setting the resting membrane potential. Here, we report that systemic injection of the chemotherapy agent paclitaxel time-dependently downregulates the expression of K 2p 1.1 mRNA and its coding K2p 1.1 protein in the DRG neurons. ⋯ Mechanically, the downregulation of DRG K 2p 1.1 mRNA is attributed to paclitaxel-induced increase in DRG DNMT3a, as blocking this increase reverses the paclitaxel-induced the decrease of DRG K2p 1.1 and mimicking this increase reduces DRG K2p 1.1 expression. In addition, paclitaxel injection increases the binding of DNMT3a to the K 2p 1.1 gene promoter region and elevates the level of DNA methylation within this region in the DRG. These findings suggest that DNMT3a-triggered downregulation of DRG K2p 1.1 may contribute to chemotherapy-induced neuropathic pain.
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Spinal cord stimulation has been shown to improve pain relief and reduce narcotic analgesic use in cases of complex refractory pain syndromes. However, a subset of patients ultimately undergoes removal of the spinal cord stimulator (SCS) system, presumably because of surgical complications or poor efficacy. This retrospective study addresses the paucity of evidence regarding risk factors and underlying causes of spinal cord stimulation failures that necessitate this explantation. ⋯ The authors' findings provide insight regarding the mechanisms of spinal cord stimulation failure that resulted in total removal of the implanted system. The relationship between spinal cord stimulation failure and certain psychiatric disorders, such as PTSD, depression, and anxiety, is highlighted. Ultimately, this work may shed light on potential avenues to reduce morbidity and improve patient outcomes.