Dexmedetomidine relieves formaldehyde-induced pain in rats through both α2 adrenoceptor and imidazoline receptor

Zhang, Hong; Yan, Xiang; Wang, Degui; Leng, Yufang; Wan, Zhang; Liu, Yongqiang; Zhang, Yan

doi:10.1016/j.biopha.2017.04.047

Cited by 18 publications

(11 citation statements)

References 27 publications

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“…The concentrations of DEX (25 μg/kg) and Atip (250 μg/kg) used in the present study were based on previous work (Cui et al, ; Si et al, ) and on a binding affinity ratio of 10:1 for the agonist‐antagonist (Virtanen, Savola, & Saano, ). The IRs (I 1 R, I 2 R, I 3 R) are another class of DEX‐binding receptors that have mainly been investigated for their involvement in anesthesia and analgesia (H. Zhang, Yan, et al, ). Increasing evidence suggests that α2‐AR and I 2 R may act coordinately in the pathogenesis of many diseases (Dahmani et al, ; F. Zhang et al, ).…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine ameliorates lipopolysaccharide‐induced acute kidney injury in rats by inhibiting inflammation and oxidative stress via the GSK‐3β/Nrf2 signaling pathway

Feng

Guan

Zhao

et al. 2019

Journal Cellular Physiology

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Acute kidney injury (AKI) is a frequent and serious complication of sepsis; however, there are currently no effective therapies. Inflammation and oxidative stress are the major mechanisms implicated in lipopolysaccharide (LPS)‐induced AKI. Dexmedetomidine (DEX) has been reported to have remarkable anti‐inflammatory and antioxidant effects. Here, we examined the renoprotective effects of DEX and potential underlying mechanisms in rats with LPS‐induced AKI. We analyzed renal function and structure; serum inflammatory cytokine; renal oxidant and antioxidant levels; and renal expression of glycogen synthase kinase‐3β (GSK‐3β)/nuclear factor erythroid 2‐related factor 2 (Nrf2) pathway‐related proteins in rats 4 hr after administration of LPS. Pretreatment with DEX improved renal function and significantly reduced the levels of inflammatory cytokines and oxidative stress markers. Treatment with DEX and the GSK‐3β inhibitor SB216367 promoted phosphorylation of GSK‐3β, induced Nrf2 nuclear translocation, and increased transcription of the Nrf2 target genes heme oxygenase‐1 and NAD(P)H quinone oxidoreductase‐1, primarily in renal tubules. Alpha‐2‐adrenergic receptor (α2‐AR) antagonist atipamezole and imidazoline I 2 receptor (I 2R) antagonist idazoxan reversed the effects of DEX. These results suggest that the renoprotective effects of DEX are mediated via α2‐AR and I 2R‐dependent pathways that reduce inflammation and oxidative stress through GSK‐3β/Nrf2 signaling.

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Section: Discussionmentioning

confidence: 99%

Dexmedetomidine ameliorates lipopolysaccharide‐induced acute kidney injury in rats by inhibiting inflammation and oxidative stress via the GSK‐3β/Nrf2 signaling pathway

Feng

Guan

Zhao

et al. 2019

Journal Cellular Physiology

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“…Related studies showed that Dex is a highly selective α adrenergic receptor agonist. It has excellent anti-anxiety as well as strong analgesic and sedative effects (23). According to literature, Dex can reduce the output of sympathetic nerves by increasing the output of parasympathetic nerves, thereby inhibiting the activity of sympathetic nerves (24).…”

Section: Discussionmentioning

confidence: 99%

Effect of dexmedetomidine anesthesia on respiratory function in pediatric patients undergoing retinoblastoma resection

et al. 2019

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The aim of this study was to investigate the effect of dexmedetomidine (Dex) on the respiratory function during anesthesia induction in pediatric patients undergoing retinoblastoma (RB) resection. A total of 87 pediatric patients who underwent RB resection in Yidu Central Hospital of Weifang were recruited into this study. General anesthesia was first induced for all patients, of which 45 were randomly assigned to the experimental group and received Dex through an intravenous infusion pump to maintain general anesthesia. The remaining 42 patients were assigned to the control group and received saline through an intravenous infusion pump. Respiratory function and hemodynamic indexes at five time-points, i.e., before anesthesia induction (T0), 5 min after injection of anesthetic agents (T1), before intubation (T2), 15 min after intubation (T3), and 30 min after extubation (T4), were recorded and compared. Incidence of perioperative cardiac and respiratory adverse events was counted in both groups, and post-anesthesia resuscitation was evaluated and compared. Compared with T0, the respiratory rate (R) of the experimental group was lower at T1-T4, but there was no statistical difference (P<0.05). Compared with T0, the control group had a higher R at T2, lower R at T3 and T4 (P<0.05), and there was no significant difference in R between T0 and T1 (P>0.05). At the same time-point, compared with the experimental group, the R was higher at T2, and lower at T3 and T4 in the control group (P<0.05), and no significant difference was found at T1. Blood oxygen saturation (SpO 2 ) of the experimental group was slightly lower than that of T0 at T1-T4 (P>0.05). In the control group, the levels of SpO 2 were significantly lower at T1-T4 than those at T0 (P<0.05). Compared with the experimental group at the same time-point, SpO 2 of the control group at T1-T4 decreased significantly (P<0.05). The heart rate (HR) of the experimental and control groups was lower at T1-T4 than that at T0 (P<0.05). The HR of the experimental group was higher than that of the control group at T1-T4 (P<0.05). Mean arterial pressure (MAP) of the experimental and control groups was lower at T1-T4 than that at T0 (P<0.05). MAP of the control group was higher than that of the experimental group at T2 but lower than that at T0 of the control group. MAP of the control group was lower than that of the experimental group at T1-T4. There was no significant difference in incidence of tachycardia, bradycardia, vomiting, hypoxia and laryngism between the two groups (P>0.05). There was no difference in resuscitation and extubation time between the two groups (P>0.05). Finally, agitation of the control group was more severe than that of the experimental group (P<0.05). Therefore, Dex can improve the respiratory function and hemodynamic stability during anesthesia induction in children with RB resection.

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“…The pain modulatory actions of α2-adrenoceptors at both the spinal 13 – 15 and supraspinal 16 levels have been extensively explored. The activation of α2-adrenoceptors by agonists was effective in alleviating the neuropathic pain state in both animals 14 , 17 and humans. 18 Dexmedetomidine (DEX), a highly selective agonist of α2-adrenergic receptors with sedative properties, has been promoted for its palpable analgesic effect through intrathecal or systemic administration.…”

Section: Introductionmentioning

confidence: 99%

Dexmedetomidine attenuates persistent postsurgical pain by upregulating K<sup>+</sup>–Cl<sup>−</sup> cotransporter-2 in the spinal dorsal horn in rats

Dai¹,

Qi²,

Fu³

et al. 2018

JPR

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BackgroundDexmedetomidine (DEX) could have an analgesic effect on pain transmission through the modulation of brain-derived neurotrophic factor (BDNF). In addition, KCC2-induced shift in neuronal Cl− homeostasis is crucial for postsynaptic inhibition mediated by GABAA receptors. Accumulating evidence shows that nerve injury, peripheral inflammation and stress activate the spinal BDNF/TrkB signal, which results in the downregulation of KCC2 transport and expression, eventually leads to GAGAergic disinhibition and hyperalgesia. The aim of this experiment was to explore the interaction between DEX and KCC2 at a molecular level in rats in the persistent postsurgical pain (PPSP).MethodsPPSP in rats was evoked by the skin/muscle incision and retraction (SMIR). Mechanical hypersensitivity was assessed with the Dynamic Plantar Aesthesiometer. Western blot and immunofluorescence assay were used to assess the expressions of related proteins.ResultsIn the first part of our experiment, the results revealed that the BDNF/TrkB-KCC2 signal plays a critical role in the development of SMIR-evoked PPSP; the second part showed that intraperitoneal administrations of 40 µg/kg DEX at 15 min presurgery and 1 to 3 days post-surgery significantly attenuated SMIR-evoked PPSP. Simultaneously, SMIR-induced KCC2 downregulation was partly reversed, which coincided with the inhibition of the BDNF/TrkB signal in the spinal dorsal horn. Moreover, intrathecal administrations of KCC2 inhibitor VU0240551 significantly reduced the analgesic effect of DEX on SMIR-evoked PPSP.ConclusionThe results of our study indicated that DEX attenuated PPSP by restoring KCC2 function through reducing BDNF/TrkB signal in the spinal dorsal horn in rats, which provides a new insight into the treatment of chronic pain in clinical postsurgical pain management.

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Dexmedetomidine relieves formaldehyde-induced pain in rats through both α2 adrenoceptor and imidazoline receptor

Cited by 18 publications

References 27 publications

Dexmedetomidine ameliorates lipopolysaccharide‐induced acute kidney injury in rats by inhibiting inflammation and oxidative stress via the GSK‐3β/Nrf2 signaling pathway

Dexmedetomidine ameliorates lipopolysaccharide‐induced acute kidney injury in rats by inhibiting inflammation and oxidative stress via the GSK‐3β/Nrf2 signaling pathway

Effect of dexmedetomidine anesthesia on respiratory function in pediatric patients undergoing retinoblastoma resection

Dexmedetomidine attenuates persistent postsurgical pain by upregulating K<sup>+</sup>–Cl<sup>−</sup> cotransporter-2 in the spinal dorsal horn in rats

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Dexmedetomidine relieves formaldehyde-induced pain in rats through both α2 adrenoceptor and imidazoline receptor

Cited by 18 publications

References 27 publications

Dexmedetomidine ameliorates lipopolysaccharide‐induced acute kidney injury in rats by inhibiting inflammation and oxidative stress via the GSK‐3β/Nrf2 signaling pathway

Dexmedetomidine ameliorates lipopolysaccharide‐induced acute kidney injury in rats by inhibiting inflammation and oxidative stress via the GSK‐3β/Nrf2 signaling pathway

Effect of dexmedetomidine anesthesia on respiratory function in pediatric patients undergoing retinoblastoma resection

Dexmedetomidine attenuates persistent postsurgical pain by upregulating K<sup>+</sup>&ndash;Cl<sup>&minus;</sup>&nbsp;cotransporter-2 in the spinal dorsal horn in rats

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Dexmedetomidine attenuates persistent postsurgical pain by upregulating K<sup>+</sup>–Cl<sup>−</sup> cotransporter-2 in the spinal dorsal horn in rats