Nogo‐A promotes inflammatory heat hyperalgesia by maintaining TRPV‐1 function in the rat dorsal root ganglion neuron. Issue 1 (19th July 2018)

• Record Type: Journal Article
• Authors: Hu, Fang; Liu, Huai-Cun; Su, Dong-Qiang; Chen, Hai-Jing; Chan, Sun-On; Wang, Yun; Wang, Jun
• Is Part Of: FASEB journal. Volume 33:Issue 1(2019)
• Page Start: 668
• Page End: 682
• Publication Date: 2018-07-19
• Subjects: RTN4A -- inflammatory pain -- cytoskeleton; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.201800382RR
• Languages: English
• ISSNs: 0892-6638

Abstract

ABSTRACT: Nogo‐A is a key inhibitory molecule of axon regeneration in oligodendrocytes. However, little is known about its role in adult neurons. In this study, we showed an important function of Nogo‐A on regulation of inflammatory pain in dorsal root ganglion (DRG) neurons. In adult rats with complete Freund's adjuvant (CFA) hind paw inflammation, DRG neurons showed a significant increase in Nogo‐A expression. Disruption of Nogo‐A signaling with Nogo‐66 receptor antagonist peptide, Nogo‐A blocking antibody, Nogo‐A short hairpin RNA, or Nogo‐A gene knockout attenuated CFA‐induced inflammatory heat hyperalgesia. Moreover, disruption of Nogo‐A signaling suppressed the function and expression in DRG neurons of the transient receptor potential vanilloid subfamily member (TRPV)‐1 channel, which is known to be the endogenous transducer of noxious heat during inflammation. These effects were accompanied with a reduction in LIM domain kinase (LIMK)/cofilin phosphorylation and actin polymerization. Similar disruption of actin filament architecture by direct action of Latrunculin A reduced the TRPV‐1 activity and up‐regulation of TRPV‐1 protein caused by CFA. We conclude that Nogo‐A plays an essential role in the development of inflammatory heat hyperalgesia, partly through maintaining TRPV‐1 function via activation of the LIMK/cofilin pathway, which regulates actin filament dynamics. These findings support a therapeutic potential of modulating Nogo‐A signaling in pain management.—Hu, F., Liu, H.‐C., Su, D.‐Q., Chen, H.‐J., Chan, S.‐O., Wang, Y., Wang, J. Nogo‐A promotes inflammatory heat hyperalgesia by maintaining TRPV‐1 function in the rat dorsal root ganglion neuron. FASEB J. 33, 668–682 (2019). www.fasebj.org