TRPV2 is required for mechanical nociception and the stretch-evoked response of primary sensory neurons

Kimiaki Katanosaka,Yuki Katanosaka,Satomi Takatsu,Keiji Naruse,Kazue Mizumura

doi:10.1038/s41598-018-35049-4

Kimiaki Katanosaka, Yuki Katanosaka + Show 3 more

Open Access

https://doi.org/10.1038/s41598-018-35049-4

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Abstract

Mechanotransduction plays important roles in many sensory processes, including touch, pain, hearing, and proprioception. However, the molecular mechanisms of mechanical nociception have remained unclear. Here, we showed that elimination of transient receptor potential vanilloid 2 (TRPV2) in mice resulted in the deficit of mechanical nociception due to the lack of mechanosensitivity in a subclass of adult primary sensory neurons (PSNs). The PSN-specific TRPV2-deficient mice showed behavioural impairment of mechanical nociception in tail-pressure and von Frey hair tests, without defects in axonal growth and neuronal composition. Conversely, the mice displayed normal behaviour to noxious heat and non-noxious tactile stimuli. Furthermore, based on the stretch-evoked Ca2+ response of cultured PSNs, we characterised two types of stretch-activated neurons in normal mice; fast-decay high-threshold and slow-decay low-threshold mechanosensitive. The cultured neurons from TRPV2-deficient mice lacked stretch-evoked Ca2+ responses by fast-decay neurons normally activated by high-threshold mechanical stimulation. These results demonstrated that TRPV2 has a critical role in mechanical nociception in the adult somatosensory system.

Highlights

Mechanosensation is essential for many biological functions, but the underlying mechanisms are largely unknown
To confirm the Wnt1-Cre derived transient receptor potential vanilloid 2 (TRPV2) gene-knockout in adult dorsal root ganglia (DRG) neurons, we examined the expression of TRPV2 proteins by immunostaining and western blotting in TRPV2flox/flox; Wnt1-Cre mice (TRPV2-deficient mice)
TRPV2-positive neuron was not detected in DRG from TRPV2-deficient mice showed no expression of TRPV2 (Fig. 1b,d)

Summary

Introduction

Mechanosensation is essential for many biological functions, but the underlying mechanisms are largely unknown. A subpopulation of PSNs expresses transient receptor potential vanilloid 2 (TRPV2), which is a thermo- and mechano-sensitive ion channel[1,2] expressed in various other tissues[3]. TRPV2 participates in a number of cellular physiological and pathological events such as stretch-induced Ca2+-influx related to maintenance of cardiomyocytes[4] and cardiomyopathy[5], cell migration and phagocytosis in macrophages[6,7], mechanical enhancement of neurite growth and development of embryonic peripheral neurons[8], and regulation of intestinal movement by intrinsic neurons in the enteric plexus[9]. The role of TRPV2 in the mechanosensory function of adult PSNs has not been well characterised. To examine the physiological roles of TRPV2 in mechanical nociception, we generated PSN-specific TRPV2-deficient mice analysed their behaviour and cellular responses to mechanical stimuli

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Results

Conclusion