ObjectiveTo observe and evaluate the effect of a single intravenous injection of low-dose esketamine on post-operative pain and post-partum depression (PPD) in cesarean delivery patients.MethodsA total of 210 patients undergoing elective cesarean delivery under combined spinal-epidural anesthesia were divided into an esketamine group (Group S, n = 105) and a normal saline group (Group L, n = 105) by a random number table. At 5 min after childbirth, patients in the S group were given 0.25 mg/kg esketamine, whereas patients in the L group received an equal volume of saline. The primary outcomes included post-operative pain control according to the Numerical Rating Scale (NRS) and the incidence of PPD according to the Edinburgh Post-partum Depression Scale (EPDS). The secondary outcomes included analgesia-related adverse events and Ramsay sedation scores.ResultsThis clinical study was a prospective, randomized, double-blind trial. A total of 210 patients were enrolled in this study. The NRS pain (cough pain) score was lower in the S group than in the L group at 24 h after surgery (P = 0.016), and there was no significant difference in resting pain and mobilization pain at 4, 8, and 48 h after surgery or resting pain at 24 h after surgery between the two groups. There was no significant difference in the prevalence of PPD between the two groups on the day before delivery, or at the first week, the second week, or the fourth week after childbirth. At 5 min after dosing, the incidence of hallucinations (P < 0.001) and dizziness (P < 0.001) was higher in the S group than in the L group. At 15 min after dosing, the incidence of dizziness (P < 0.001) and nausea (P = 0.011) was higher in the S group than in the L group. The incidence of dizziness (P < 0.001) was higher in the S group than in the L group when leaving the operating room. The Ramsay scores in Group S were lower than in Group L at 5 min (p < 0.001), 15 min (p < 0.001) after dosing and at the time of leaving the operating room (p < 0.001).ConclusionIn this study, a single intravenous injection of 0.25 mg/kg esketamine did not reduce the incidence of depression at 1, 2, or 4 w post-partum but improved pain during exercise at 24 h post-operatively under the conditions of this clinical trial.Clinical trial registration[www.chictr.org.cn], identifier [ChiCTR2100054332].

Background: To observe the effects of MMP-9 (matrix metalloproteases-9) on the mechanical allodynia and thermal hyperalgesia and the expression of CX3CL1 (CX3C chemokine ligand 1) protein in the spinal dorsal root ganglion (DRG) in rats with chronic sciatic nerve constriction injury (CCI).Methods: A total of 84 male SD rats were randomly divided into seven groups, namely the normal group , the sham operation group , the model group , the CCI + MMP-9 group, the CCI + TIMP-1 group , the CCI + siRNA group, and the CCI + MM-siRNA group. The CCI model was prepared 5 days after implantation of intrathecal catheter. The rat paw mechanical withdrawal threshold (PWMT) and paw thermal withdrawal latency (PWTL) were measured 1 day before CCI surgery and 1, 2, 3 and 5 days after CCI respectively.Western blot (WB) was used to detect the expressions of the MMP-9 and the CX3CL1 protein in the L5 DRG of the spinal cord 1 day after CCI operation.Results: (I) Behavioral assessment of hyperalgesia: compared with the Sham group, the PWMT and PWTL of the CCI group were significantly reduced at each time point after CCI surgery; compared with the CCI group, the PWMT and PWTL of the CCI + MMP-9 group decreased 1 day after CCI; for the PWMT and PWTL of the CCI + TIMP-1 group and CCI + siRNA group, PWMT and PWTL increased 1 day after CCI; (II) the expressions of MMP-9 and CX3CL1 protein in the DRG of the spinal cord: compared with Sham group, the expressions of MMP-9 and CX3CL1 protein in the DRG of the CCI group increased significantly 1 day after CCI surgery; compared with the CCI group, the expressions increased in the CCI + MMP-9 group 1 day after CCI . However, the expressions of MMP-9 and CX3CL1 in the CCI + TIMP-1 group and CCI + siRNA group were reduced on the first postoperative day. Conclusions:The mechanism of MMP-9 participating in the early phase of neuropathic pain (NP) in CCI rats is related to the upregulation of CX3CL1.

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