Spinal WNT pathway contributes to remifentanil induced hyperalgesia through regulating fractalkine and CX3CR1 in rats. (28th October 2016)

• Record Type: Journal Article
• Authors: Gong, Gu; Hu, Ling; Qin, Fuen; Yin, Liang; Yi, Xiaobo; Yuan, Libang; Wu, Wei
• Is Part Of: Neuroscience letters. Volume 633(2016)
• Page Start: 21
• Page End: 27
• Publication Date: 2016-10-28
• Subjects: CX3CL1 chemokine (CX3C motif) ligand 1 -- FZ frizzled -- GAPDH glyceraldehydes 3-phosphate dehydrogenase -- i.t. intrathecally -- i.v. intravenously -- NMDA N-methyl-d-aspartate -- NS normal saline -- PWL paw withdrawal thermal latency -- PWT Paw withdrawal mechanical threshold -- OIH opioid-induced hyperalgesia -- SD standard deviation -- TSS titanic stimulation of the sciatic nerve; Remifentanil -- Opioid-induced hyperalgesia -- WNT3a -- β-catenin -- Fractalkine; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2016.09.006
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: Remifentanil anesthesia could elicit postoperative mechanical and thermal hyperalgesia. Up-regulation of WNT3a, FZ8 and β-catenin in spinal dorsal horn in remifentanil-induced postoperative hyperalgesia. Changes of spinal fractalkine and CX3CR1 expression in remifentanil-induced postoperative hyperalgesia. Intrathecal delivery of Fz-8/Fc and anti-CX3CR1 could attenuate remifentanil-induced postoperative hyperalgesia. WNT inhibition could reduce spinal fractalkine and CX3CR1 expression in remifentanil-induced postoperative hyperalgesia. Abstract: Background: Tremendous experimental and clinical studies identify that remifentanil anesthesia might elicit postoperative opioid-induced hyperalgesia (OIH) and aggravate nociceptive hypersensitivity, whereas definite mechanisms remain equivocal. WNT signaling and fractalkine pathway have been manifested to participate in varieties of pain pathogenesis, respectively, but no report is on whether they could lead to OIH. This study intended to investigate the effect of WNT3a/β-catenin on fractalkine and its receptor CX3CR1 in OIH in rats model of incision pain. Methods: A WNT scavenger Fz-8/Fc and a neutralizing antibody against CX3CR1 (anti-CX3CR1) were injected intrathecally after remifentanil infusion. Exogenous WNT agonist delivery was utilized in naïve rats. PWT and PWL were documented for postsurgical 48 h to assess mechanical and thermal hyperalgesia. Also, expressions of WNT3a, FZ1, FZ8, β-catenin, fractalkine and CX3CR1 in spinal dorsal horn were measured by Western blot and RT-qPCR after nociceptive testing. Results: We found that postsurgical mechanical and thermal hyperalgesia could be engendered after remifentanil exposure, which was accompanied by a dramatical rise of spinal WNT3a, FZ8, β-catenin, fractalkine and CX3CR1 levels. Moreover, OIH was attenuated by intrathecal application of Fz-8/Fc and anti-CX3CR1. Up-regulation of spinal fractalkine and CX3CR1 expression after remifentanil anesthesia was reversed by Fz-8/Fc. Also, WNT agonist administration could directly generate hypernociception and elevate fractalkine/CX3CR1 level in naïve rats, which was prevented by anti-CX3CR1. Conclusion: These present findings demonstrated that the involvement of spinal WNT3a/FZ8/β-catenin in OIH through modulating fractalkine/CX3CR1 in rats.