Zhang XL(1), Lai RC(2), Chen ZH(3), Zhong XX(4), Cao XY(5)(6), Zhang X(3), Xiao YB(3), Wang JC(2), Liu XG(3), Xie MX(2). Author information:
(1)Medical Research Center of Guangdong Provincial People's Hospital, Guangdong
Academy of Medical Sciences, Guangzhou, China.
(2)Department of Anesthesiology, Sun Yat-sen University Cancer Center, State Key
Laboratory of Oncology in South China, Collaborative Innovation Center for
Cancer Medicine, Guangzhou, China.
(3)Zhongshan School of Medicine of Sun Yat-sen University, Guangzhou, China.
(4)The First Affiliated Hospital of Southern University of Science and
Technology, the Second Clinical Medical College of Jinan University, Shenzhen
People's Hospital, Shenzhen, China.
(5)College of Food Science and Technology, Hainan University, Haikou, China.
(6)State Key Laboratory of Marine Resources Utilization of South China Sea,
Mechanical allodynia is a debilitating condition for millions of patients with chronic pain. Mechanical allodynia can manifest in distinct forms, including brush-evoked dynamic and filament-evoked static allodynia. In the nervous system, the forkhead protein Foxo1 plays a critical role in neuronal structures and functions. However, the role of Foxo1 in the somatosensory signal remains unclear. Here, we found that Foxo1 selectively regulated static mechanical pain. Foxo1 knockdown decreased sensitivity to static mechanical stimuli in normal rats and attenuated static mechanical allodynia in rat models for neuropathic, inflammatory, and chemotherapy pain. Conversely, Foxo1 overexpression selectively enhanced sensitivity to static mechanical stimuli and provoked static mechanical allodynia. Furthermore, Foxo1 interacted with voltage-gated sodium Nav1.7 channels and increased the Nav1.7 current density by accelerating activation rather than by changing the expression of Nav1.7 in dorsal root ganglia neurons. In addition, the serum level of Foxo1 was found to be increased in chronic pain patients and to be positively correlated with the severity of chronic pain. Altogether, our findings suggest that serum Foxo1 level could be used as a biological marker for prediction and diagnosis of chronic pain. Moreover, selective blockade of Foxo1/Nav1.7 interaction may offer a new therapeutic approach in patients with mechanical pain.
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