Neuron-restrictive silencer factor in periaqueductal gray contributes to remifentanil-induced postoperative hyperalgesia via repression of the mu-opioid receptor
| Autor: | Mingjian Kong, Juan Zhang, Yue Liu, Jianhua He, Zhengliang Ma, Yu Zhou, Li Xu, Cui'e Lu, Linyu Shi, Xiaoping Gu |
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| Rok vydání: | 2015 |
| Předmět: |
Agonist
medicine.drug_class Receptors Opioid mu Remifentanil Pharmacology Periaqueductal gray Mice Piperidines Opioid receptor medicine Animals Periaqueductal Gray Receptor Injections Intraventricular business.industry Oligonucleotides Antisense Mice Inbred C57BL Repressor Proteins Disease Models Animal Treatment Outcome Nociception nervous system Neurology Hyperalgesia Anesthesia Neurology (clinical) medicine.symptom μ-opioid receptor business medicine.drug |
| Zdroj: | Journal of the Neurological Sciences. 352:48-52 |
| ISSN: | 0022-510X |
| DOI: | 10.1016/j.jns.2015.03.018 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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