Dexmedetomidine Relieves Acute Inflammatory Visceral Pain in Rats through the ERK Pathway, Toll-Like Receptor Signaling, and TRPV1 Channel

Liu, Yatao; Liu, Wei; Wang, Xiaoqing; Wan, Zhang; Liu, Yongqiang; Leng, Yufang

doi:10.1007/s12031-018-1172-5

Cited by 38 publications

(27 citation statements)

References 46 publications

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“…We randomly divided twenty SD rats into four groups (n=5): normal group (rats given no treatment), model group (treated with acetic acid), vehicle group (subdural administration of 10 mL saline), and DEX group (intrathecal injection of 3 mg DEX). Fifteen minutes after the subdural administration with saline/DEX, acetic acid (3%, 300 mg/kg) was injected into the peritoneal cavity, and the rats were observed for 30 min . The pain behaviour was assessed by abdominal withdrawal reflex (AWR), thermal withdrawal latency (TWL), and mechanical withdrawal threshold (MWT).…”

Section: Methodsmentioning

confidence: 99%

Nrf2 mediates the antinociceptive activity of dexmedetomidine in an acute inflammatory visceral pain rat model by activating the NF‐κB sensor

Lan

Zheng

Feng

et al. 2019

Cell Biochemistry & Function

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Dexmedetomidine (DEX) is a highly selective α2 adrenoceptor agonist. In this study, we evaluated the antalgic effect of DEX on acetic acid-induced acute inflammatory visceral pain (AIVP) in rats. Additionally, we evaluated the role of Nrf2 signalling in antinociception. We administered acetic acid to male Sprague Dawley rats that were treated with DEX or saline. Twenty rats were randomly classified into the following groups: normal, model, vehicle, or DEX group. Both q-RT PCR and enzyme-linked immunosorbent assay data suggested that interleukin 1β (IL-1β), tumour necrosis factor α, and IL-6 were upregulated in the spinal cord. Western blotting and q-RT PCR analyses were performed to detect the protein and mRNA expression levels of Nrf2, Keap1, and HO-1 in the spinal cord. The DEX group exhibited a significant downregulation in Nrf2/Keap1/HO-1 signal activation compared with the model group.Furthermore, we used the Nrf2 -/knockout AIVP rat model to determine the role of Nrf2 in the antinociceptive effect of DEX. We observed that the Nrf2 knockout blocked the Keap1/Nrf2/HO-1 signal transduction and partially abated the antinociceptive and the anti-inflammatory effects of DEX. Moreover, our data also indicated that DEX treatment decreased the activation and expression of nuclear factor (NF)-κB. However, Nrf2 silencing restored the expression of NF-κB and its phosphorylated form to physiological levels. In summary, our results suggested that Nrf2 signalling plays an important role in the antinociceptive effect of DEX in the AIVP rat model and that Nrf2 exerts its function by enhancing the activation of the NF-κB sensor.Significance of the study: Currently, using the behavioural parameters is not adequate for the diagnosis of AIVP, and there are no studies that have investigated the role and the mechanism of DEX in ameliorating visceral pain. In this study, we demonstrated that acetic acid stimulation in rats induces AIVP. Additionally, the administration of DEX inhibited the acute inflammation response and decreased the visceromotor reaction (behavioural) to algesia. Further, DEX inhibited the Keap1/ Nrf2 pathway, which was activated by acetic acid treatment. We suggest that suppressing the inflammatory response could partially regulate the antinociceptive effect of DEX through Nrf2-mediated NF-κB activation associated with AIVP.

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Section: Methodsmentioning

confidence: 99%

Nrf2 mediates the antinociceptive activity of dexmedetomidine in an acute inflammatory visceral pain rat model by activating the NF‐κB sensor

Lan

Zheng

Feng

et al. 2019

Cell Biochemistry & Function

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“…[30] Therefore, some antiin ammatory drugs can also alleviate CRBD. Another study showed that Dex reduces the release of prostaglandins of in ammation, and hence, relieves CRBD [31]. In addition, Dex exerts a sedative effect and relieves CRBD [10].…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine intravesical instillation reduces postoperative catheter-related bladder discomfort in male patients under general anesthesia: a randomized controlled study

Chen

Wang

et al. 2020

Preprint

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Background The catheter-related bladder discomfort (CRBD) of male patients is a common clinical problem, albeit lacking effective solutions. The present study aimed to investigate whether dexmedetomidine intravesical instillation alleviates the postoperative urinary discomfort in male patients with catheter under general anesthesia. Methods This single-blinded, prospective, randomized study included a total of 167 male patients American Society of Anesthesiologists (ASA) physical status I-II scheduled for surgery under general anesthesia were allocated to two groups: 84 in the dexmedetomidine (Dex) group and 83 in the control group. Dex group patients received intravesical instillation of the drug 0.5 μg/kg and normal saline 20 mL, while the control group received intravesical instillation of 20 mL normal saline. The catheter was clamped for 30 min after intravesical instillation for all patients. Bladder stimulation scales and urethra pain numerical rating scale (NRS) scores were measured at admittance to post-anesthesia care unit (PACU) (T0), intravesical instillation (T1), 30 min (T2), 60 min (T3), 2 h (T4) after intravesical instillation, discharged from PACU (T5), and 6 h (T6) and 24 h (T7) after the operation. Patient satisfaction at discharge from PACU and 24 h post-operation were compared between the two groups. Results Bladder stimulation scales and urethra pain NRS scores after 30 min of dexmedetomidine intravesical instillation to 24 h post-operation were significantly lower than the control group (p<0.001), and patient satisfaction was higher at discharge from PACU and 24 h post-operation (p<0.001). No diﬀerences were detected in Steward score out of PACU (p=0.213) and from the time of the end of operation to fully awake (p=0.417). Conclusion Dex intravesical instillation reduces postoperative urinary discomfort and urethra pain and improves satisfaction in male patients under general anesthesia.

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“…[30] Therefore, some anti-in ammatory drugs can also alleviate CRBD. Another study showed that Dex reduces the release of prostaglandins of in ammation, and hence, relieves CRBD [31]. In addition, Dex exerts a sedative effect and relieves CRBD [10].…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine intravesical instillation reduces postoperative catheter-related bladder discomfort in male patients under general anesthesia: a randomized controlled study

Chen

Wang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background The catheter-related bladder discomfort (CRBD) of male patients is a common clinical problem, albeit lacking effective solutions. The present study aimed to investigate whether dexmedetomidine intravesical instillation alleviates the postoperative urinary discomfort in male patients with catheter under general anesthesia.Methods This single-blinded, prospective, randomized study included a total of 167 male patients American Society of Anesthesiologists (ASA) physical status I-II scheduled for surgery under general anesthesia were allocated to two groups: 84 in the dexmedetomidine (Dex) group and 83 in the control group. Dex group patients received intravesical instillation of the drug 0.5 µg/kg and normal saline 20 mL, while the control group received intravesical instillation of 20 mL normal saline. The catheter was clamped for 30 min after intravesical instillation for all patients. Bladder stimulation scales and urethra pain numerical rating scale (NRS) scores were measured at admittance to post-anesthesia care unit (PACU) (T0), intravesical instillation (T1), 30 min (T2), 60 min (T3), 2 h (T4) after intravesical instillation, discharged from PACU (T5), and 6 h (T6) and 24 h (T7) after the operation. Patient satisfaction at discharge from PACU and 24 h post-operation were compared between the two groups.Results Bladder stimulation scales and urethra pain NRS scores after 30 min of dexmedetomidine intravesical instillation to 24 h post-operation were significantly lower than the control group (p < 0.001), and patient satisfaction was higher at discharge from PACU and 24 h post-operation (p < 0.001). No differences were detected in Steward score out of PACU (p = 0.213) and from the time of the end of operation to fully awake (p = 0.417).Conclusion Dex intravesical instillation reduces postoperative urinary discomfort and urethra pain and improves satisfaction in male patients under general anesthesia.Clinical Trial Registration: Chinese Clinical Trial Registry (No. ChiCTR1800016429), date of registration 1st June 2018

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Dexmedetomidine Relieves Acute Inflammatory Visceral Pain in Rats through the ERK Pathway, Toll-Like Receptor Signaling, and TRPV1 Channel

Cited by 38 publications

References 46 publications

Nrf2 mediates the antinociceptive activity of dexmedetomidine in an acute inflammatory visceral pain rat model by activating the NF‐κB sensor

Nrf2 mediates the antinociceptive activity of dexmedetomidine in an acute inflammatory visceral pain rat model by activating the NF‐κB sensor

Dexmedetomidine intravesical instillation reduces postoperative catheter-related bladder discomfort in male patients under general anesthesia: a randomized controlled study

Dexmedetomidine intravesical instillation reduces postoperative catheter-related bladder discomfort in male patients under general anesthesia: a randomized controlled study

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