Parathyroid hormone-related peptide activates and modulates TRPV1 channel in human DRG neurons. Eur J Pain 2018 Oct;22(9):1685-1690
Date
05/26/2018Pubmed ID
29797679DOI
10.1002/ejp.1251Scopus ID
2-s2.0-85053414226 (requires institutional sign-in at Scopus site) 7 CitationsAbstract
Parathyroid hormone-related peptide (PTHrP) is associated with advanced tumor growth and metastasis, especially in breast, prostate and myeloma cancers that metastasize to bones, resulting in debilitating chronic pain conditions. Our recent studies revealed that the receptor for PTHrP, PTH1R, is expressed in mouse DRG sensory neurons, and its activation leads to flow-activation and modulation of TRPV1 channel function, resulting in peripheral heat and mechanical hypersensitivity. In order to verify the translatability of our findings in rodents to humans, we explored whether this signalling axis operates in primary human DRG sensory neurons. Analysis of gene expression data from recently reported RNA deep sequencing experiments performed on mouse and human DRGs reveals that PTH1R is expressed in DRG and tibial nerve. Furthermore, exposure of cultured human DRG neurons to PTHrP leads to slow-sustained activation of TRPV1 and modulation of capsaicin-induced channel activation. Both activation and modulation of TRPV1 by PTHrP were dependent on PKC activity. Our findings suggest that functional PTHrP/PTH1R-TRPV1 signalling exists in human DRG neurons, which could contribute to local nociceptor excitation in the vicinity of metastatic bone tumor microenvironment.
Author List
Shepherd AJ, Mickle AD, McIlvried LA, Gereau RW 4th, Mohapatra DPAuthor
Aaron David Mickle PhD Associate Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultAnimals
Capsaicin
Cell Culture Techniques
Female
Ganglia, Spinal
Humans
Male
Mice
Pain
Parathyroid Hormone-Related Protein
Sensory Receptor Cells
Signal Transduction
TRPV Cation Channels
Young Adult
