ABSTRACT
BACKGROUND: Dexmedetomidine (DEX) has been used as an anesthetic for decades. The present investigation aimed to elucidate the analgesic impact of DEX on 2,4,6-Trinitrobenzenesulfonic acid (TNBS)-induced chronic inflammatory visceral pain (CIVP) in rats. METHODS: TNBS with or without DEX to Male Sprague-Dawley SD rats were randomly divided into four groups: normal, CIVP, DEX, and vehicle. Pain behaviors were assessed and the abdominal withdrawal reflex, mechanical withdrawal threshold, and thermal withdrawal latency were recorded. Quantitative polymerase chain reaction data showed increased expressions of pro-inflammatory cytokines (IL-6, IL-1ß and TNF-α) in the spinal cord tissues of rats. RESULTS: RNA microarray and quantitative polymerase chain reaction results indicated that miR-34a was downregulated by TNBS induction, but it was upregulated by DEX administration. Further studies showed that transfection of adenovirus-miR-34a inhibitor reversed the effect of DEX on the pain behaviors and spinal-cord pro-inflammatory-cytokine generation in CIVP rats. Additionally, we found that miR-34a targeted the 3'-UTR of the HDAC2 gene, as evinced by the increased HDAC2 expression in the CIVP and DEX + miR-34a inhibitor groups, and decreased HDAC2 signaling in the DEX group. Moreover, knock-down of HDAC2 restored DEX-attenuated pain behaviors and reduced pro-inflammatory cytokine production. CONCLUSIONS: DEX thus exhibited an analgesic effect on CIVP rats through the miR-34a-mediated HDAC2 pathway and suppressed visceral hypersensitivity.
Subject(s)
Dexmedetomidine/pharmacology , Histone Deacetylase 2/metabolism , MicroRNAs/metabolism , Visceral Pain/therapy , 3' Untranslated Regions , Animals , Chronic Pain/therapy , Cytokines/metabolism , Down-Regulation , Histone Deacetylase 2/genetics , Hypnotics and Sedatives/pharmacology , Male , Microarray Analysis , Pain Threshold , Polymerase Chain Reaction , Random Allocation , Rats, Sprague-Dawley , Reflex , Spinal Cord/metabolism , Trinitrobenzenesulfonic Acid/adverse effects , Up-Regulation , Visceral Pain/chemically inducedABSTRACT
BACKGROUND: Transversus abdominis plane block (TAPB) has been proven to be an effective means of postoperative anesthesia, but the optimum effective concentration of ropivacaine warrants further research. OBJECTIVE: This study aimed to identify the optimal ropivacaine concentration of TAPB using a meta-analysis. MATERIALS AND METHODS: This study consisted of a meta-analysis of randomized controlled trials (RCTs). We searched online databases, including PubMed, Embase, the Cochrane Database of Systematic Reviews, and Web of Science. RCTs investigating the 24-hour postoperative opioid consumption and the rest and dynamic pain scores 2, 12, and 24 hours after surgery were included in this analysis. We also assessed opioid-related side-effects and patient satisfaction 24 hours after surgery. RESULTS: Nineteen RCTs (1217 patients) were included in this meta-analysis, which showed that only TAPB with 0.375% and 0.5% ropivacaine was able to reduce opioid consumption 24 hours after surgery by weighted mean differences of -6.55 and -4.44 mg (morphine IV equivalents), respectively (P<0.05). A meta-regression analysis did not reveal an association between the local anesthetic dose (in mg), surgery, anesthesia, block timing, and the TAPB effect on opioid consumption. Ropivacaine concentrations of 0.375% and 0.5% reduced the 2-hour postoperative pain score and reduced the incidence of nausea and vomiting, but this analgesic effect disappeared at 12 and 24 hours. Only TAPB with 0.375% ropivacaine improved the degree of satisfaction 24 hours after surgery (weighted mean difference of 0.87 [0.08-1.66], P=0.03). CONCLUSION: In terms of efficacy and safety, the use of 0.375% ropivacaine for TAPB is preferred in the clinical work.
