Neuropathic pain (NP) is difficult to treat due to complex pathophysiological mechanisms. Pulsed radiofrequency (RRF) has been used widely with neuromodulation effect in refractory chronic pain treatment. A recent study found that PRF treatment may decrease chronic pain-related anxiety-depressant symptoms in patients, even though the mechanisms are unclear. Additionally, accumulated evidence has shown serotonin uptake is correlated with various neuropsychiatric diseases. Therefore, we investigated the effects and underlying mechanisms of PRF on depression-like behaviors, resulting from spared nerve injury (SNI)-induced NP. We examined the indexes of mechanical allodynia, cold allodynia, depression-like behavior, and blood cytokines by dynamic plantar aesthesiometry, acetone spray test, forced swimming test, and ProcartaPlex multiplex immunoassays in male Wistar rats, respectively. Serotonin transporters (SERTs) in rat brains were examined by using 4-[18F]-ADAM/PET imaging. We found that specific uptake ratios (SURs) of SERTs were significantly decreased in the brain regions of the thalamus and striatum in rats with SNI-induced NP and depression-like behaviors. Additionally, the decrease in SERT density was correlated with the development of a depression-like behavior indicated by the forced swimming test results and pronounced IL-6 cytokines. Moreover, we demonstrated that PRF application could modulate the descending serotoninergic pathway to relieve pain and depression behaviors.

Background: Kidney transplantation (KT) improves survival and quality of life in patients with end-stage kidney disease; however, long-term allograft survival remains a major challenge. Brain natriuretic peptide (BNP), a biomarker of cardiorenal stress and volume status, may be associated with early postoperative physiological changes after KT. This study evaluated the association between early postoperative BNP changes and long-term allograft survival, and explored the potential role of BNP-derived parameters in relation to graft outcomes. Methods: This retrospective cohort study included adult recipients of deceased-donor KT between 2009 and 2018. Patients were categorized according to early graft function. Serum BNP levels were measured preoperatively and within postoperative 24 h, and the percentage increase (dBNP ratio) was calculated. Cox regression and receiver operating characteristic analyses were used to identify risk factors for graft failure and evaluate the discriminatory performance of BNP-derived biomarkers, respectively. Results: Among the 179 recipients, postoperative BNP levels and dBNP ratios differed significantly across graft function groups, with higher values in delayed graft function. After multivariate adjustment, the dBNP ratio remained significantly associated with graft failure (hazard ratio, 1.16; 95% confidence interval, 1.10–1.21; p < 0.001). Additionally, the dBNP ratio demonstrated better discriminatory performance for graft failure compared with postoperative BNP alone (area under the curve, 0.815 vs. 0.596; p < 0.001), with an exploratory cutoff of approximately 18%. Recipients with a dBNP ratio ≥ 18% had poorer early graft function, lower longitudinal estimated glomerular filtration rates, and significantly reduced graft survival. Conclusions: An increased early postoperative dBNP ratio was significantly associated with adverse long-term kidney allograft outcomes. However, given the potential for residual confounding, these findings should be interpreted as associative and hypothesis-generating rather than predictive.