- •Sustained infusion of remifentanil induces postoperative hyperalgesia in mice.
- •NRSF and MOR protein expression levels in PAG were changed in this model.
- •NRSF antisense oligonucleotide pretreatment inhibited MOR downregulation in the PAG.
- •Blockade of NRSF alleviated remifentanil induced postoperative hyperalgesia.
- •NRSF repressing MOR participated in remifentanil-induced postoperative hyperalgesia.
The ultra-short-acting mu-opioid receptor (MOR) agonist remifentanil induces postoperative hyperalgesia both in preclinical and clinical research studies. However, the precise mechanisms remain unclear, although changes in opioid receptor expression might be a correlative feature. Neuron-restrictive silencer factor (NRSF) functions as a crucial regulator of MOR expression in specific neuronal cells. Using a mouse model of incisional postoperative pain, we assessed the expression of MOR and NRSF and investigated whether disruption of NRSF expression could prevent the postoperative nociceptive sensitization induced by surgical incision and subcutaneous infusion of remifentanil.
Paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were independently used to assess mechanical allodynia and thermal hyperalgesia after surgery and cerebral ventricle injection of NRSF antisense oligonucleotide. Western blotting analyses were preformed to assess the expression levels of MOR and NRSF.
NRSF expression levels were enhanced after intraoperative infusion of remifentanil, resulting in repression of MOR expression in the periaqueductal gray (PAG). NRSF blockade with an NRSF antisense oligonucleotide significantly enhanced the expression levels of MOR and alleviated mechanical allodynia and thermal hyperalgesia induced by intraoperative infusion of remifentanil.
NRSF functions as a negative regulator of MOR in PAG and contributes to remifentanil-induced postoperative hyperalgesia. NRSF in PAG may be a potential target for this pain therapy.
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Published online: March 19, 2015
Accepted: March 11, 2015
Received in revised form: March 10, 2015
Received: December 6, 2014
© 2015 Elsevier B.V. Published by Elsevier Inc. All rights reserved.