ABSTRACT
Introduction: Glycopyrrolate is commonly researched as a preoperative medication or in conjunction with cholinesterase inhibitors to counteract the lingering muscarinic effects of non-depolarizing muscarinic agents. However, studies have yielded inconsistent results regarding the superiority of glycopyrrolate over other anti-cholinergic drugs, such as atropine, particularly its effect on heart rate, blood pressure (BP), and glandular secretions. This study aimed to evaluate the differences in perioperative oral secretions, hemodynamics, and recovery quality with glycopyrrolate versus those with atropine before anesthesia induction in children undergoing tonsillectomy and adenoidectomy. Methods: In this prospective, single-center, randomized, double-blind, controlled trial, a total of 103 children were randomly assigned to group A (n = 51, glycopyrrolate 0.005 mg/kg) or B (n = 52, atropine 0.01 mg/kg). The follow-up anesthetic induction and maintenance protocols were the same in both groups. Vital signs, duration of surgery, extubation time, degree of wetness around the vocal cords during tracheal intubation, weight of oral secretions, and perioperative complications were recorded. Results: No significant differences were observed in the degree of wetness around the vocal cords during tracheal intubation, as well as in the weight of oral secretions, duration of surgery, or extubation time, between the two groups. The intraoperative and postoperative heart rates were lower in group A than in group B (110.18 ± 10.58 vs. 114.94 ± 11.14, p = 0.028; 96.96 ± 10.81 vs. 103.38 ± 10.09, p = 0.002). The differences observed in the intraoperative and preoperative heart rates were lower in group A than in group B (23.84 ± 9.62 vs. 29.65 ± 8.75, p = 0.002). The differences observed in the postoperative and preoperative heart rates were lower in group A than in group B (10.63 ± 9.97 vs. 18.09 ± 9.39, p = 0.000). Conclusion: Glycopyrrolate showed a smoother change in heart rate than atropine during and after tonsillectomy and adenoidectomy, with no effect on BP or recovery quality, and did not increase oral secretions. The findings indicate that glycopyrrolate can serve as an alternative to atropine to prevent secretions in anesthesia induction for tonsillectomy and adenoidectomy in children. Trial registration: This study was registered with the Chinese Clinical Trial Registry (Registration Number: ChiCTR2200063578; Date of Registration: 12/09/2022).
ABSTRACT
OBJECTIVE: To explore the role of spinal microglial CX3CR1/ERK5 pathway in the development of neuropathic pain. METHODS: The model of spinal nerve ligation (SNL) was established by ligating the L5 spinal nerve with 6-0 silk thread in male Sprague Dawley rats. The expression of activated ERK5 (p-ERK5) was examined by immunohistochemistry test. To detect the role of ERK5 in neuropathic pain, PWT and PWL were measured after an intrathecal knockdown of ERK5. For determining the regulating effect of CX3CL1/CX3CR1 on the activity of microglial ERK5, CX3CR1 was blocked by an intrathecal injection of anti-rat CX3CR1 antibody and the activity of spinal ERK5 tested. Then whether an intrathecal knockdown of ERK5 could reverse the effect of CX3CL1 on pain hypersensitivity and microglia activation was investigated. RESULTS: ERK5 was activated in spinal microglia after SNL compared to the sham group (61.75 ± 11.52 vs 2.2 ± 0.12; 58.01 ± 10.45 vs 1.1 ± 0.11) . The knockdown of ERK5 by an intrathecal injection of antisense oligonucleotides suppressed the mechanical (15.42 ± 3.46 vs 22.73 ± 3.21g; 13.63 ± 2.88 vs. 21.42 ± 4.12g) and thermal hyperalgesia (13.48 ± 2.01) vs (18.05 ± 3.71) s; (11.6 ± 2.33) vs (17.73 ± 1.42) s induced by nerve injury. The blockage of CX3CR1, a receptor of CX3CL1, significantly reduced the level of ERK5 activation following SNL (30.12 ± 8.60) vs (58.25 ± 11.5); (49.5 ± 12.12) vs (35.51 ± 3.74) (P < 0.05). In addition, the antisense knockdown of ERK5 reversed the CX3CL1-induced hyperalgesia and spinal microglia activation. CONCLUSIONS: CX3CL1/CX3CR1 regulates nerve injury-induced pain hypersensitivity through ERK5.
