Inhibition of DOR prevents remifentanil induced postoperative hyperalgesia through regulating the trafficking and function of spinal NMDA receptors in vivo and in vitro

Wang, Chunyan; Li, Yize; Wang, Haiyun; Xie, Keliang; Shu, Ruichen; Zhang, Lin-Lin; Hu, Nan; Yu, Yonghao; Wang, Guolin

doi:10.1016/j.brainresbull.2014.12.001

Cited by 33 publications

(21 citation statements)

References 46 publications

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“…Another possible explanation is an effect via DOR which is shown to participate in remifentanil-induced hyperalgesia. 32 A gradual withdrawal of remifentanil may allow some kind of adaptation of membrane DOR that prevents hyperalgesia.…”

Section: Discussionmentioning

confidence: 99%

Gradual withdrawal of remifentanil infusion may prevent opioid-induced hyperalgesia

Comelon

Ræder

Stubhaug

et al. 2016

British Journal of Anaesthesia

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Section: Discussionmentioning

confidence: 99%

Gradual withdrawal of remifentanil infusion may prevent opioid-induced hyperalgesia

Comelon

Ræder

Stubhaug

et al. 2016

British Journal of Anaesthesia

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“…δ ‐opioid receptor antagonists may, therefore, prevent the enhancement effect of remifentanil on the NMDA receptor‐mediated miniature excitatory post synaptic current in dorsal horn neurons. Naltrindole, a δ ‐opioid receptor antagonist, at a dose of 30 nM infused 10 min before remifentanil, was found to attenuate remifentanil‐induced mechanical and thermal hyperalgesia, without affecting baseline nociceptive threshold .…”

Section: Non‐opioid Adjuncts In Preventing Remifentanil‐induced Acutementioning

confidence: 97%

Remifentanil tolerance and hyperalgesia: short‐term gain, long‐term pain?

et al. 2016

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SummaryThe unique pharmacology of remifentanil makes it a popular intra-operative analgesic. Short-acting opioids like remifentanil have been associated with acute opioid tolerance and/or opioid-induced hyperalgesia, two phenomena which have different mechanisms and are pharmacologically distinct. Clinical studies show heterogeneity of remifentanil infusion regimens, durations of infusion, maintenance of anaesthesia, cumulative dose of remifentanil and pain measures, which makes it difficult to draw conclusions about the incidence of acute tolerance or hyperalgesia. However, it appears that intra-operative remifentanil infusion rates of above 0.25 lg.kg À1.min À1 are associated with higher postoperative opioid consumption, suggesting tolerance. Infusion rates greater than 0.2 lg.kg À1.min À1 are characterised by lower mechanical/pressure/cold/pain thresholds, which suggests hyperalgesia. The use of concurrent multimodal analgesia, especially N-methyl-D-aspartate receptor antagonists, may be an effective preventive strategy.The clinical significance and long-term consequences of these entities is still uncertain.

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“…Several studies indicated that the membrane trafficking of DOR increased in vivo and in vitro in morphine-tolerant mice, indicating that membrane insertion of DOR has an important role in opioid-induced tolerance and hyperalgesia (31,32). Other studies demonstrated that the high sensitivity to opioid-induced mechanical and thermal pain was prevented with the application of naltrindole, suggesting that naltrindole may be a potential anti-hyperalgesic agent for treating OIH (24,33).…”

Section: Discussionmentioning

confidence: 99%

Δ-opioid receptor inhibition prevents remifentanil-induced post‑operative hyperalgesia via regulating GluR1 trafficking and AMPA receptor function

Liu

Wang

Wang³

et al. 2017

Exp Ther Med

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Abstract. The interaction of remifentanil with glutamate systems has an important role in remifentanil-induced thermal and mechanical hyperalgesia. A previous study by our group suggested that the trafficking and function of glutamate receptor 1 (GluR1) subunits contributes to remifentanil-induced hyperalgesia by regulating the phosphorylation of GluR1 in dorsal horn neurons. The present study demonstrated that δ opioid receptor (DOR) inhibition prevented thermal and mechanical hyperalgesia, which was induced by remifentanil infusion via attenuating GluR1 subunit trafficking and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) function in dorsal horn neurons. Sprague Dawley rats received a plantar incision and remifentanil infusion to induce a model of postoperative hyperalgesia. Thermal and mechanical pain was tested at 8 different time-points. Expression of AMPAR subunits GluR1 and DOR, as well as the phosphorylation status of GluR1 were evaluated by western blot analysis. Furthermore, the function of AMPAR in the spinal dorsal horn was measured by whole-cell patch-clamp recording. Remifentanil-induced thermal and mechanical hyperalgesia appeared after the 60-min infusions, reaching a peak level on day 2 and persisting for 5 days. Remifentanil infusion led to upregulation of membrane expression of the AMPAR subunit GluR1 and DOR (P=0.003 and 0.001, respectively) no change in total GluR1 and DOR expression levels (P=0.244 and 0.531, respectively). Selective DOR inhibitor naltrindole caused a reduction of remifentanil-induced hyperalgesia, which was accompanied by downregulation of membrane levels of GluR1 in the spinal cord (P=0.0013). In addition, DOR inhibition led to downregulation of GluR1 phosphorylated at Ser845. Furthermore, the AMPAR-mediated miniature excitatory post-synaptic current was increased in frequency and in amplitude in dorsal horn neurons (P=0.002 and 0.0011, respectively), which was decreased by incubation with naltrindole. Combined behavioral, western blot and electrophysiological evidence indicated that remifentanil-induced hyperalgesia was mediated by DOR activation, followed by phosphorylation-dependent GluR1 trafficking and AMPAR function enhancement in the spinal cord. DOR appears to be required for remifentanil and incision-induced hyperalgesia development and to be a potential biochemical target for treating opioid-induced postoperative hyperalgesia.

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Inhibition of DOR prevents remifentanil induced postoperative hyperalgesia through regulating the trafficking and function of spinal NMDA receptors in vivo and in vitro

Cited by 33 publications

References 46 publications

Gradual withdrawal of remifentanil infusion may prevent opioid-induced hyperalgesia

Gradual withdrawal of remifentanil infusion may prevent opioid-induced hyperalgesia

Remifentanil tolerance and hyperalgesia: short‐term gain, long‐term pain?

Δ-opioid receptor inhibition prevents remifentanil-induced post‑operative hyperalgesia via regulating GluR1 trafficking and AMPA receptor function

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