BackgroundNeurodegeneration is associated with changes in basal cellular function due to the dysregulation of autophagy. A recent study introduced the involvement of autophagy during spinal nerve ligation (SNL). Nefopam has shown potential for reducing neuropathic pain, but the underlying mechanisms are unknown. Here, we investigated the effects of nefopam on neuropathic pain development following SNL, focusing on the involvement of autophagy.MethodsThe functional role of nefopam in capsaicin-induced autophagy was assessed by human glioblastoma M059 K cells. The neuropathic pain model was used to determine whether the effect of nefopam on pain control was mediated through autophagy control. Neuropathic pain was induced by L5 and L6 SNL in male rats randomized into three groups: Group S (sham-operated), Group C (received normal saline), and Group E (received nefopam). A behavioral test using a von Frey was examined. Expression changes of autophagy in response to nefopam was analyzed in spinal cord tissues (L4-L6) by immunoblotting and immunohistochemistry.ResultsThe paw withdrawal threshold examined on days 3, 5, 7, and 14 post-SNL was significantly higher in Group E than in Group C. SNL increased the levels of microtubule-associated protein 1 light chain 3B (LC3B-1), with concomitant reduction of sequestosome 1 (SQTSM1/p62), compared with Group S, indicating that SNL induced autophagy. These effects were reversed by nefopam injection, and the results were confirmed by immunohistochemistry for LC3-I/II. Furthermore, SNL-mediated JNK activation was markedly decreased following nefopam injection. Hematoxylin and eosin staining on Day 14 post-SNL revealed that SNL caused lymphocyte infiltration and oligodendrocyte localization in the substantia gelatinosa of the dorsal gray horn, which were reduced by nefopam injection.ConclusionCollectively, the mode of action of nefopam on neuropathic pain appears to be associated with downregulation of phospho-JNK and autophagy, as well as modulation of the immune response.
The incidence of postoperative shivering related to sufentanil was less than that related to remifentanil, with no significant differences in the intraoperative core temperatures.
Surgical procedures, as well as anesthetics, affect stress hormones and proinflammatory cytokines. Therefore, we investigated the effect of two different anesthetic techniques on intraoperative hormonal stress responses and interleukin-6 (IL-6) in patients with chronic renal disease undergoing arteriovenous fistula formation. Eighteen patients aged above 20 years were randomly divided into two groups: group A (n=8) with axillary brachial plexus block and group MAC (n=10) with monitored anesthesia care (MAC) using dexmedetomidine. The levels of epinephrine, norepinephrine, cortisol, glucose, IL-6, and heat shock protein 70 (HSP70) were recorded at pre-anesthesia (T0) and end of surgery (T3). No significant differences in epinephrine and HSP70 were observed between these two groups or within each group. Norepinephrine was significantly decreased in group MAC compared with group A at T3 (p=0.001), but no significant differences were found within each group. The cortisol level in group MAC significantly decreased at T3 compared with T0 (p=0.028). The glucose level in group MAC significantly increased at T3 compared with T0 (p=0.019). No significant differences in IL-6 levels were observed within each group. In conclusion, in this study, neither monitored anesthesia nor regional anesthesia influenced stress hormones and proinflammatory cytokines in patients undergoing arteriovenous fistula formation, but significant changes in cortisol and glucose levels were observed in the group receiving dexmedetomidine.
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