Highlights
- •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.
Abstract
Background
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.
Methods
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.
Results
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.
Conclusion
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.
Keywords
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Article info
Publication history
Published online: March 19, 2015
Accepted:
March 11,
2015
Received in revised form:
March 10,
2015
Received:
December 6,
2014
Identification
Copyright
© 2015 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
