title: Sodium channel Nav1.7 expression is upregulated in the dorsal root ganglia in a rat model of paclitaxel-induced peripheral neuropathy.
abstract: Paclitaxel-induced peripheral neuropathy is not completely known. Since the sodium channel Nav1.7 has been implicated in pain perception, and is upregulated in pain disorders, we investigated the effect of paclitaxel on Nav1.7 expression in rat dorsal root ganglion (DRG) neurons. Thirty Sprague-Dawley rats were administered either 2 mg/kg paclitaxel or vehicle on days 0, 2, 4 and 6. To evaluate nociceptive responses, paw withdrawal threshold (PWT) was measured by von Frey anesthesiometer on days 7, 14 and 21 after first paclitaxel administration. Expression of Nav1.7 in DRG was measured by real-time RT-PCR and Western blot. PWT was also measured in rats that received dorsal root ganglionic injection of either Nav1.7 antibody, neutralized Nav1.7 antibody or no injection (sham surgery) (n = 5/group). Average PWT was lower in animals administered paclitaxel than those administered vehicle at days 7 (P< 0.05), 14 (P< 0.01), and 21 (P< 0.01). DRG Nav1.7 mRNA and protein levels were higher in animals administered paclitaxel than those administered vehicle on days 7, 14 and 21 (allP< 0.05). PWT decrease was significantly correlated with increased Nav1.7 protein levels on days 7 (r = -0.88,P= 0.04), 14 (r = -0.46,P= 0.03) and 21 (r = -0.27,P= 0.01) after first paclitaxel administration. In animals that received sham surgery, neutralized Nav1.7 antibody or Nav1.7 antibody, PWTs were significantly reduced 7 days after first paclitaxel administration (allP< 0.05), but PWTs of animals that received Nav1.7 antibody were higher than those that received neutralized Nav1.7 antibody (P< 0.05). These results indicate that increased DRG Nav1.7 expression may be partially responsible for paclitaxel-induced peripheral neuropathy.
authors: Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, 430060 Hubei Province People's Republic of China.
authors: Zhongyuan
authors: Z
authors: Xia
authors: Department of Anesthesiology, Renmin Hospital, Hubei University of Medicine, No.39, Chaoyang Road, Maojian District, Shiyan City, 442000 Hubei Province People's Republic of China.
authors: Yun
authors: Y
authors: Xiao
authors: Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, 430060 Hubei Province People's Republic of China.
authors: Yang
authors: Y
authors: Wu
authors: Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, 430060 Hubei Province People's Republic of China.
authors: Bo
authors: B
authors: Zhao
keywords: Dorsal root ganglion; Paclitaxel; Peripheral neuropathy; Sodium channel Nav1.7