BACKGROUND: Perioperative fentanyl has been reported to induce hyperalgesia and increase postoperative pain. In this study, we tried to investigate behavioral hyperalgesia, the expression of proinflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and the activation of microglia in the spinal cord and dorsal root ganglion (DRG) in a rat model of surgical plantar incision with or without perioperative fentanyl. METHODS: Four groups of rats (n = 32 for each group) were subcutaneously injected with fentanyl at 60 μg/kg or normal saline for 4 times with 15-minute intervals. Plantar incisions were made to rats in 2 groups after the second drug injection. Mechanical and thermal nociceptive thresholds were assessed by the tail pressure test and paw withdrawal test on the day before, at 1, 2, 3, 4 hours, and on the days 1–7 after drug injection. The lumbar spinal cord, bilateral DRG, and cerebrospinal fluid of 4 rats in each group were collected to measure IL-1β, IL-6, and TNF-α on the day before, at the fourth hour, and on the days 1, 3, 5, and 7 after drug injection. The lumbar spinal cord and bilateral DRG were removed to detect the ionized calcium-binding adapter molecule 1 on the day before and on the days 1 and 7 after drug injection. RESULTS: Rats injected with normal saline only demonstrated no significant mechanical or thermal hyperalgesia or any increases of IL-1β, IL-6, and TNF-α in the spinal cord or DRG. However, injection of fentanyl induced analgesia within as early as 4 hours and a significant delayed tail mechanical and bilateral plantar thermal hyperalgesia after injections lasting for 2 days, while surgical plantar incision induced a significant mechanical and thermal hyperalgesia lasting for 1–4 days. The combination of fentanyl and incision further aggravated the hyperalgesia and prolonged the duration of hyperalgesia. The fentanyl or surgical incision upregulated the expression of IL-1β, IL-6, and TNF-α in the spinal cord and bilateral DRG for more than 7 days and increase of ionized calcium-binding adapter molecule 1 in the spinal cord. The combination of fentanyl and incision resulted in higher increase of IL-1β, IL-6, and TNF-α in the spinal cord and bilateral DRG. CONCLUSIONS: The surgical plantar incision with or without perioperative fentanyl induced significant mechanical and thermal hyperalgesia, an increased expression of IL-1β, IL-6, TNF-α in the spinal cord and DRG, and activation of microglia in the spinal cord.

Chronic stress exposure increases the risk of developing various neuropsychiatric illnesses. The ventral hippocampus (vHPC) is central to affective and cognitive processing and displays a high density of acetylcholine (ACh) muscarinic receptors (mAChRs). However, the precise role of vHPC mAChRs in anxiety remains to be fully investigated. In this study, we found that chronic restraint stress (CRS) induced social avoidance and anxiety-like behaviors in mice and increased mAChR expression in the vHPC. CRS increased the vHPC ACh release in behaving mice. Moreover, CRS altered the synaptic activities and enhanced neuronal activity of the vHPC neurons. Using pharmacological and viral approaches, we showed that infusing the antagonist of mAChRs or decreasing their expression in the vHPC attenuated the anxiety-like behavior and rescued the social avoidance behaviors in mice probably due to suppression of vHPC neuronal activity and its excitatory synaptic transmission. Our results suggest that the changes of neuronal activity and synaptic transmission in the vHPC mediated by mAChRs may play an important role in stress-induced anxiety-like behavior, providing new insights into the pathological mechanism and potential pharmacological target for anxiety disorders.

Background: Rhomboid intercostal block (RIB) is a new regional anesthesia technique that provides postoperative analgesia for breast surgery and thoracoscopic surgery. The published papers are not yet fully integrated and do not adequately address the impact and safety of the RIB on postoperative pain.Methods: The PubMed, Web of Science and Embase were searched from 2016 to 2021 for all available randomized controlled trials (RCTs) that evaluated the analgesic efficacy and safety of RIB after thoracic surgery and breast surgery. Random and fixed-effects meta-analytical models were used where indicated, and between-study heterogeneity was assessed. The primary outcome was Postoperative Numerical Rating Scale (NRS) scores of patients at rest recorded 0–1, 6–8, 24 h after surgery. The secondary outcomes included rate of postoperative nausea and vomiting (PONV), postoperative fentanyl consumption and presence of complications of the block.Results: From 81 records identified, four studies met our inclusion criteria, including 216 patients (RIB:108 patients; no block: 108 patients). In the primary outcome, RIB group showed significantly lower postoperative NRS at rest at first 0–1 h and 6–8 h (weighted mean difference [WMD] = -1.55; 95% confidence internal [CI] = -2.92 to -0.19;p < 0.05), (WMD = -0. 69; 95% CI = -1.29 to -0. 09; p < 0. 05). And there was no significant difference between groups in NRS at rest at 24 h (WMD = -0.78; 95% CI = -1.64 to -0.08;p = 0.77). Also, RIB group showed significantly lower postoperative NRS of breast surgery and thoracoscopic surgery at 0-1 h (WMD = -3.00; 95% CI = -3.13 to -2.87;p < 0.01), (WMD = -1.08; 95% CI = -1.98 to -0.18;p < 0.05). In the secondary outcome, the analysis also showed RIB group had significant lower of POVN rates (summary relative risk (RR) = 0.212;95%CI = 0.10 to 0.45;p < 0. 01) and the postoperative consumption of fentanyl (WMD = -57.52;95%CI = -106.03 to -9.02;p < 0. 05).Conclusion: This review shows that RIB was more effective in controlling acute pain after breast surgery and thoracoscopic surgery than general analgesia. And it is a trend that RIB may be a kind of effective and safe nerve bock technology and it requires further studies.