2. Academic Validation
  3. Activation of NPFFR2 leads to hyperalgesia through the spinal inflammatory mediator CGRP in mice

Activation of NPFFR2 leads to hyperalgesia through the spinal inflammatory mediator CGRP in mice

  • Exp Neurol. 2017 May:291:62-73. doi: 10.1016/j.expneurol.2017.02.003.
Ya-Tin Lin 1,  Ho-Ling Liu 2,  Yuan-Ji Day 3,  Che-Chien Chang 4,  Po-Hung Hsu 5,  Jin-Chung Chen 6
Affiliations

Affiliations

  • 1 Graduate Institute of Biomedical Sciences, Department of Physiology and Pharmacology, Chang Gung University, No. 259 Wen-Hwa 1st Rd., Taoyuan, 333, Guishan, Taiwan. Electronic address: [email protected].
  • 2 Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, No. 1400 Pressler St., TX 77030-4009, Houston, USA. Electronic address: [email protected].
  • 3 Department of Anesthesiology, Hualein Tzu Chi Hospital & Tzu Chi University, Tzu Chi Foundation, No. 707, Chung Yang Rd., 970 Hualien, Taiwan. Electronic address: [email protected].
  • 4 Department of Chemistry, Fu Jen Catholic University, No. 510, Zhongzheng Road, Xinzhuang Dist. 242, New Taipei City, Taiwan. Electronic address: [email protected].
  • 5 Department of Electrical Engineering, Chang Gung University, Taoyuan, Taiwan; Center for Advanced Molecular Imaging and Translation, Chang Gung Memorial Hospital, Taoyuan, Taiwan. Electronic address: [email protected].
  • 6 Graduate Institute of Biomedical Sciences, Department of Physiology and Pharmacology, Chang Gung University, No. 259 Wen-Hwa 1st Rd., Taoyuan, 333, Guishan, Taiwan; Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan; Neuroscience Research Center, Chang Gung Memorial Hospital, No. 5, Fusing St., Taoyuan, 333, Guishan, Taiwan. Electronic address: [email protected].
PMID: 28179153 DOI: 10.1016/j.expneurol.2017.02.003
Abstract

Neuropeptide FF (NPFF) is recognized as an opioid modulating peptide that regulates morphine-induced analgesia. The aim of this study was to delineate the role of NPFFR2 in pain transmission. We found the expression levels of NPFF and NPFFR2 were increased in the lumbar dorsal horn of Animals with CFA- and carrageenan-induced inflammation and both NPFFR2 over-expressing transgenic (NPFFR2-Tg) and NPFFR2 agonist-treated mice displayed hyperalgesia. BOLD signals from functional MRI showed that NPFFR2-Tg mice exhibited increased activation of pain-related brain regions after painful stimulation when compared to WT mice. Inflammatory mediators within the spinal cord, Calcitonin gene-related peptide (CGRP) and substance P (SP), were up-regulated in NPFFR2-Tg and chronic NPFFR2 agonist-treated mice. In DRG cultures, treatment with an NPFFR2 Agonist induced the expression and release of CGRP, an action which was blocked by NPFFR2 siRNA. Furthermore, treatment with a CGRP antagonist ameliorated the pain hyperalgesia in NPFFR2-Tg mice, returning the pain threshold to a control level. However, treatment with a SP antagonist reduced the pain responses in both WT and NPFFR2-Tg mice and did not suppress pain hypersensitivity in NPFFR2-Tg mice. Together, these results demonstrate that NPFFR2 activation modulates pain transmission by up-regulating the pain mediator CGRP, leading to hyperalgesia.

Keywords

CGRP; DRG; Hyperalgesia; NPFFR2; Neuropeptide FF (NPFF); Pain transmission.

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