Neural Regeneration Research ›› 2019, Vol. 14 ›› Issue (1): 140-148.doi: 10.4103/1673-5374.243719

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Effects of TRPA1 activation and inhibition on TRPA1and CGRP expression in dorsal root ganglion neurons

Xiao-Lei Wang1, Li-Wei Cui2, Zhen Liu1, Yue-Ming Gao1, Sheng Wang1, Hao Li3, Hu-Xiang Liu1, Ling-Jia Yu1   

  1. 1 Department of Rheumatology, Qilu Hospital of Shandong University, Jinan, Shandong Province, China
    2 Department of Respiratory Medicine, Qilu Hospital of Shandong University, Jinan, Shandong Province, China
    3 Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, Shandong Province, China
  • Online:2019-01-15 Published:2019-01-15
  • Contact: Ling-Jia Yu, BS, aolin88@126.com.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81501935 (to HL); the Natural Science Foundation of Shandong Province of China, No. ZR2014HQ065 (to HL).

Abstract:

Transient receptor potential ankyrin 1 (TRPA1) is a key player in pain and neurogenic inflammation, and is localized in nociceptive primary sensory dorsal root ganglion (DRG) neurons. TRPA1 plays a major role in the transmission of nociceptive sensory signals. The generation of neurogenic inflammation appears to involve TRPA1-evoked release of calcitonin gene-related peptide (CGRP). However, it remains unknown whether TRPA1 or CGRP expression is affected by TRPA1 activation. Thus, in this study, we examined TRPA1 and CGRP expression in DRG neurons in vitro after treatment with the TRPA1 activator formaldehyde or the TRPA1 blocker menthol. In addition, we examined the role of extracellular signal-regulated protein kinase 1/2 (ERK1/2) in this process. DRG neurons in culture were exposed to formaldehyde, menthol, the ERK1/2 inhibitor PD98059 + formaldehyde, or PD98059 + menthol. After treatment, real-time polymerase chain reaction, western blot assay and double immunofluorescence labeling were performed to evaluate TRPA1 and CGRP expression in DRG neurons. Formaldehyde elevated mRNA and protein levels of TRPA1 and CGRP, as well as the proportion of TRPA1- and CGRP-positive neurons. In contrast, menthol reduced TRPA1 and CGRP expression. Furthermore, the effects of formaldehyde, but not menthol, on CGRP expression were blocked by pretreatment with PD98059. PD98059 pretreatment did not affect TRPA1 expression in the presence of formaldehyde or menthol.

Key words: nerve regeneration, TRPA1, TRPV1, formaldehyde, menthol, CGRP, dorsal root ganglion, neuron, neurogenic inflammation, nociceptive signal, ERK1/2, neural regeneration