The Effect of Intrathecal Administration TRPA1 Antagonists in a Rat Model of Neuropathic Pain

Zhang, Wei MD; Liu, Yue MD; Zhao, Xin MD; Gu, Xiaoping PhD; Ma, Zhengliang PhD

Anesthesia & Analgesia:
doi: 10.1213/ANE.0000000000000179
Pain and Analgesic Mechanisms: Research Report
Abstract

BACKGROUND: The fact that transient receptor potential ankyrin 1 (TRPA1) on the peripheral terminals could attenuate hyperalgesia is widely accepted, but the effect of spinal TRPA1 in the modulation of hyperalgesia has not been fully demonstrated. In the present study, we investigated the effect of intrathecal (i.t.) administration TRPA1 antagonists on chronic pain and expression of TRPA1 and phosphorylation N-methyl-D-aspartate receptor 2B subunit (p-NR2B) in the spinal cord with chronic compression of the dorsal root ganglia (CCD) in rats.

METHODS: The study was conducted in 2 parts. Part 1: Sixteen rats were divided into 2 groups (n = 8 each): a sham group and CCD group. Paw withdrawal mechanical thresholds (PWMT) were measured at baseline and 1, 3, 7, 10, 14, and 21 days after CCD. Sixteen other rats were used to evaluate expression of TRPA1 and p-NR2B in spinal cord on the seventh and 14th days after CCD; Western blotting was used to evaluate expression levels (n = 4 each). Part 2: 40 rats were divided into 5 groups (n = 8 each): CCD group, CCD + Vehicle group, CCD + HC-030031(10 μg, i.t.) group, CCD + HC-030031(25 μg, i.t.) group, and CCD + HC-030031(50 μg, i.t.) group. PWMTs were measured at baseline and 0.5, 1, 2, 4, and 6 hours after i.t. HC-030031on the third, seventh, 10th, and 14th days after CCD. Another 48 rats were used to evaluate expression of TRPA1 and p-NR2B in spinal cord 2 hours after injection on the seventh and 14th days after CCD in groups CCD, CCD + Vehicle, and CCD+ HC-030031(50 μg, i.t.) using Western blotting (n = 4 each).

RESULTS: Compared with the sham group, PWMT was significantly decreased, and protein expression of TRPA1 and p-NR2B were upregulated, in spinal cord on the seventh and 14th days after CCD operation. TRPA1 antagonists (HC-030031, 50 μg, i.t.) increased the PWMT after CCD and downregulated the protein level of TRPA1 and p-NR2B in spinal cord at 2 hours after the injection on the seventh and 14th days after CCD.

CONCLUSIONS: These data demonstrated that the i.t. administration of TRPA1 antagonists could attenuate neuropathic pain in CCD rats, and this effect could be partially reduced by p-NR2B receptor expression in spinal cord.

In Brief

Published ahead of print May 22, 2014

Author Information

From the Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical Department of Nanjing University, Nanjing, Jiangsu, People’s Republic of China.

Accepted for publication November 30, 2013.

Published ahead of print May 22, 2014

Funding: This study was supported by Youth Start Fund of Nanjing Health Bureau (QYK10146), Youth Medical Experts Fund of Nanjing (Third Level) and Key Subject of Anesthesiology in Jiangsu Province, China (XK 201140) and National Nature Science Foundation of China (81070892, 81171048, 81171047, 81371207, and 81300951).

The authors declare no conflicts of interest.

Reprints will not be available from the authors.

Address correspondence to Zhengliang Ma, PhD, Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical Department of Nanjing University, Nanjing 210008, Jiangsu, People’s Republic of China. Address e-mail to zhengliangma1964@163.com.

© 2014 International Anesthesia Research Society