Background:Splanchnic denervation (SND) is an alternative interventional strategy for refractory upper abdominal cancer pain. This systematic review and meta-analysis evaluated the longitudinal analgesic efficacy, opioid-sparing effects, and safety of SND compared with those of conventional control modalities. Methods:Randomized controlled trials (RCTs) comparing SND with controls were identified by searching PubMed, Embase, CENTRAL, Scopus, and Web of Science through December 2025. The primary outcome was change from baseline (CfB) in pain intensity at 12 weeks. Secondary outcomes included CfB in morphine equivalent daily dose, quality of life (QoL), and procedure-related adverse events. Results:Six RCTs (n = 337) were included. At 12 weeks, SND demonstrated analgesic efficacy (standardized mean difference [SMD] = -0.36; 95% confidence interval [CI], -1.20 to 0.48; P = 0.323) and opioid-sparing effects (SMD = -1.01; 95% CI, -2.16 to 0.14; P = 0.071) comparable to control groups. At 4 weeks, QoL outcomes were comparable between groups (SMD = 0.70; 95% CI, -0.28 to 1.67; P = 0.127). SND was associated with a significantly lower risk of hypotension (risk ratio [RR] = 0.45; 95% CI, 0.25 to 0.80; P = 0.007) and diarrhea (RR = 0.24; 95% CI, 0.10 to 0.54; P < 0.001) than celiac plexus neurolysis. Conclusions:SND appears to be a clinically effective, technically feasible, and safe interventional strategy for refractory upper abdominal cancer pain. SND achieved efficacy comparable to conventional controls across 24 weeks. SND may serve as a clinically meaningful option in multimodal pain management for patients with advanced abdominal malignancies.
Background:Postherpetic neuralgia (PHN) causes chronic neuropathic pain and reduced quality of life. The peak width of skeletonized mean diffusivity (PSMD), based on MD histogram along the fractional anisotropy skeleton, has shown robustness and clinical relevance in other neurological disorders. Methods:This single-center cross-sectional study included 83 participants: 42 patients with PHN and 41 age- and sex-matched healthy controls. All participants underwent diffusion tensor imaging (DTI), and data were analyzed using the FMRIB Software Library software. PSMD and conventional DTI metrics were computed and compared between groups. Results:Patients with PHN exhibited marked increase in PSMD relative to healthy controls (2.862 ± 0.436 × 10-4 vs. 2.369 ± 0.407 × 10-4 mm2/s, P < 0.001). Additionally, MD and axial diffusivity (AD) were significantly elevated in the PHN group compared with controls (0.854 ± 0.035 vs. 0.836 ± 0.030, P = 0.012; 1.292 ± 0.036 vs. 1.264 ± 0.033, P < 0.001; respectively). Receiver operating characteristic analysis demonstrated that PSMD provided the greatest discriminative ability between groups (area under the curve = 0.816, P < 0.001). Furthermore, multivariable logistic regression including PSMD, MD, and AD identified PSMD as the sole independent predictor of PHN status (P = 0.002). Conclusions:This study demonstrated that patients with PHN showed altered white matter integrity, with increased PSMD, MD, and AD values compared to healthy controls. PSMD showed superior diagnostic performance over most conventional DTI metrics and may serve as promising marker of widespread white matter disruption in PHN at the group level.
Background:Trigeminal neuralgia (TN) is prevalent form of neuropathic pain (NP). Its regulatory circuits and mechanisms remain unclear. The authors' previous work demonstrated that the cerebrospinal fluid-contacting nucleus (CSF-contacting nucleus) participates in the regulation of NP induced by sciatic nerve injury via the brain-CSF circuit. However, whether it mediates NP caused by trigeminal nerve injury has not been reported. Methods:This study used viral retrograde tracing to examine neural projections between the CSF-contacting nucleus and the trigeminal ganglion (TG). Neuronal activity in TN model was assessed using immunofluorescence, and chemogenetic tools were used to test its role in pain behavior. Local calcitonin gene-related peptide (CGRP)-RAMP1-PKA signaling changes and their modulation were analyzed for effects on TN. Results:Retrograde tracing confirmed neural projections between the CSF-contacting nucleus and the TG. In TN model rats, elevated c-Fos expression indicated its activation. Chemogenetic activation induced hyperalgesia in normal rats, whereas its inhibition reduced pain in TN rats. Molecular analyses revealed upregulation of CGRP, RAMP1, and components of the PKA pathway within the nucleus. Pathway inhibition via RAMP1 knockdown or olcegepant administration attenuated pain, with knockdown effect being reversible by cAMP. Conclusions:This study reveals that the CSF-contacting nucleus is activated during TN and participates in central pain regulation through its local CGRP-RAMP1-PKA signaling pathway. Intervening in this pathway effectively modulates pain behavior, suggesting that this nucleus and its signaling system may represent novel therapeutic targets for treating TN. These findings provide experimental evidence for understanding the central mechanisms of TN and developing analgesic strategies.
Background:The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway is associated with different neurological dysfunctions in the nervous system. Although electroacupuncture (EA) has been proven to alleviate neuropathic pain (NP), its underlying mechanisms remain unclear. The role of the cGAS-STING signaling pathway in the anterior cingulate cortex (ACC) during NP and its potential association with EA-mediated analgesic effects remain unknown. Methods:The authors established an NP model by applying chronic constriction injury (CCI) to the sciatic nerve and evaluated behavioral hyperalgesia using the acetone test score and mechanical threshold. Protein distribution and expression were assessed using immunofluorescence and Western blotting, respectively. Results:cGAS and STING were predominantly expressed in neurons in the ACC of rats, and the total abundance of cGAS and STING was upregulated on both sides of the ACC following CCI. Intra-ACC administration of either RU.521 or C-176 alleviated the pain hypersensitivity caused by CCI. Moreover, EA reduced pain hypersensitivity and inhibited the CCI-induced upregulation of cGAS and STING in the ACC. Conclusions:This study demonstrates that the cGAS-STING signaling pathway is involved in the occurrence and development of NP in the ACC following peripheral nerve injury, and that EA may alleviate NP by suppressing this pathway in rats.
