Involvement of TRPA1 activation in acute pain induced by cadmium in mice

Molecular Pain

Toshio Ohta¹  Makoto Tominaga²  Shigeru Saito²  Kunitoshi Uchida²  Toshiaki Imagawa³  Kenji Takahashi¹  Saeko Miura¹ 

[1] Department of Veterinary Pharmacology, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan;Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institutes of Natural Sciences, Okazaki 444-8787, Japan;Biological Chemistry, Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan

关键词: TRPA1;    Sensory neuron;    Patch-clamp;    Pain;    Mouse;    Intracellular calcium;    Cadmium;   

Others  :  862608
DOI  :  10.1186/1744-8069-9-7

 received in 2012-11-30, accepted in 2013-02-26,  发布年份 2013

【 摘 要 】

Background

Cadmium (Cd) is an environmental pollutant and acute exposure to it causes symptoms related to pain and inflammation in the airway and gastrointestinal tract, but the underlying mechanisms are still unclear. TRPA1 is a nonselective cation channel expressed in sensory neurons and acts as a nociceptive receptor. Some metal ions such as Ca, Mg, Ba and Zn are reported to modulate TRPA1 channel activity. In the present study, we investigated the effect of Cd on cultured mouse dorsal root ganglion neurons and a heterologous expression system to analyze the effect of Cd at the molecular level. In addition, we examined whether Cd caused acute pain in vivo.

Results

In wild-type mouse sensory neurons, Cd evoked an elevation of the intracellular Ca concentration ([Ca²⁺]_i) that was inhibited by external Ca removal and TRPA1 blockers. Most of the Cd-sensitive neurons were also sensitive to cinnamaldehyde (a TRPA1 agonist) and [Ca²⁺]_i responses to Cd were absent in TRPA1(−/−) mouse neurons. Heterologous expression of TRPA1 mutant channels that were less sensitive to Zn showed attenuation of Cd sensitivity. Intracellular Cd imaging revealed that Cd entered sensory neurons through TRPA1. The stimulatory effects of Cd were confirmed in TRPA1-expressing rat pancreatic cancer cells (RIN-14B). Intraplantar injection of Cd induced pain-related behaviors that were largely attenuated in TRPA1(−/−) mice.

Conclusions

Cd excites sensory neurons via activation of TRPA1 and causes acute pain, the mechanism of which may be similar to that of Zn. The present results indicate that TRPA1 is involved in the nociceptive or inflammatory effects of Cd.

【 授权许可】

   
2013 Miura et al; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

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