The pain-relief properties of tricyclic antidepressants can be attributed to several actions. Recent observations suggest that adenosine is involved in the antinociceptive effect of amitriptyline. The A3 adenosine receptor (A3AR) is the only adenosine subtype overexpressed in inflammatory and cancer cells. This study was performed to investigate the role of A3AR in the anti-nociceptive effect of amitriptyline. Spinal nerve-ligated neuropathic pain was induced by ligating the L5 and L6 spinal nerves of male Sprague-Dawley rats. The neuropathic rats were randomly assigned to one of the following three groups (8 per group): a neuropathic pain with normal saline group, a neuropathic pain with amitriptyline group, and a neuropathic pain with amitriptyline and 3-ethyl-5-benzyl- 2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS) group. Amitriptyline or saline was administered intraperitoneally and 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS-1191), an A3AR antagonist, was injected subcutaneously immediately before amitriptyline administration. The level of extracellular signal-regulated kinase P44/42 (ERK1/2), cyclic AMP response element-binding protein (CREB), and proinflammatory cytokines were assessed using immunoblotting or reverse-transciption polymerase chain reaction. Amitriptyline increased the mechanical withdrawal threshold of the neuropathic rats. The level of phospho-ERK1/2 and phospho-CREB proteins, and proinflammatory cytokines produced by spinal nerve ligation were significantly reduced by amitriptyline administration. However, the use of MRS-1191 before amitriptyline administration not only reduced the threshold of mechanical allodynia, but also increased the signaling protein and proinflammatory cytokine levels, which were reduced by amitriptyline. The results of this study suggest that the anti-nociceptive effect of amitriptyline involves the suppression of ERK1/2 and CREB signaling proteins, and A3AR activation also affects the alleviation of the inflammatory response.
30 April 2023 in Journal of Yeungnam Medical Science
Background: Laparoscopic cholecystectomy (LC) is a noninvasive surgery, but postoperative pain is a major problem. Studies have indicated that erector spinae plane block (ESPB) has an analgesic effect after LC. We aimed to compare the efficacy of different ESPB anesthetic concentrations in pain control in patients with LC.Methods: This retrospective study included patients aged 20 to 75 years scheduled for LC with the American Society of Anesthesiologists physical status classification I or II. ESPB was administered using 0.375% bupivacaine in group 1 and 0.25% in group 2. Both groups received general anesthesia. Postoperative tramadol consumption and pain scores were compared and intraoperative and postoperative fentanyl requirements in the postanesthesia care unit (PACU) were measured.Results: Eighty-five patients were included in this analysis. Tramadol consumption in the first 12 hours, second 12 hours, and total 24 hours was similar between groups (p>0.05). The differences between postoperative numeric rating scale (NRS) scores at rest did not differ significantly. The postoperative NRS scores upon bodily movement were not statistically different between the two groups, except at 12 hours. The mean intraoperative and postoperative fentanyl requirements in the PACU were similar. The difference in the requirement for rescue analgesics was not statistically significant (p=0.788). Conclusion: Ultrasound-guided ESPB performed with different bupivacaine concentrations was effective in both groups for LC analgesia, with similar opioid consumption. A lower concentration of local anesthetic can be helpful for the safety of regional anesthesia and is recommended for the analgesic effect of ESPB in LC.
Objectives: This study aimed to investigate the epidemiology of intravenous midazolam-induced postoperative expressive aphasia (EA). Methods: The incidence rate, risk ratio, and contributing factors to intravenous midazolam-induced postoperative EA were analyzed retrospectively in 6756 orthopedic patients. A telephone interview was conducted with patients with EA after surgery. Results: Patients were allocated to either the midazolam group (n = 6178) or no-midazolam group (n = 578). Twelve patients developed EA in the midazolam group, with an incidence of 0.19%, and no patient developed EA in the no-midazolam group. The mean age of EA patients was 70 years, and 92% were women. Among them, 75% received general anesthesia, and the mean dose of midazolam was 1.8 mg. EA was reversed in nine of 12 (75%) patients within 4 minutes of flumazenil administration, and >60 minutes were required to reverse EA in the other three patients (25%). Conclusion: Intravenous midazolam administration for preoperative sedation caused transient EA in 0.19% of patients, especially elderly women who received general anesthesia, and EA could be reversed by flumazenil.
Background and Objectives: The effect of positive end-expiratory pressure (PEEP) on intraocular pressure (IOP) is debatable. There have been no studies investigating the effects of PEEP on IOP during one-lung ventilation (OLV). We aimed to investigate the effects of PEEP on IOP in patients undergoing OLV for video-assisted thoracoscopic surgery (VATs). Materials and Methods: Fifty-two patients undergoing VATs were divided into a zero-PEEP (ZEEP) and a 6 cmH2O of PEEP (PEEP) groups. IOP, ocular perfusion pressure (OPP), and respiratory and hemodynamic parameters were measured before induction (T1), immediately following endotracheal intubation (T2), 30 min (T3) and 60 min (T4) after a position change to the lateral decubitus position (LDP) and OLV, and 10 min following two-lung ventilation near the end of the surgery (T5). Results: There was no significant difference in IOP and OPP between the two groups. The IOP of the dependent eye was significantly higher than that of the non-dependent eye during LDP in both groups. Peak inspiratory pressure was significantly higher in the PEEP group than in the ZEEP group at T3–T5. Dynamic compliance was significantly higher in the PEEP group than in the ZEEP group at T2–T5. The ratio of arterial oxygen partial pressure to fractional inspired oxygen was significantly higher in the PEEP group than in the ZEEP group at T4. Conclusions: Applying 6 cmH2O of PEEP did not increase IOP but enhanced dynamic compliance and oxygenation during OLV. These results suggest that 6 cmH2O of PEEP can be safely applied during OLV in LDP.