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Papers of the Week


Papers: 18 Dec 2021 - 24 Dec 2021


Pharmacology/Drug Development


2021 Dec 20


Neuroscience

Akt/aquaporin-4 signaling aggravates neuropathic pain by activating astrocytes after spinal nerve ligation in rats.

Authors

Guo S, Song Z, He J, Yin G, Zhu J, Liu H, Yang L, Ji X, Xu X, Liu Z, Liu J
Neuroscience. 2021 Dec 20.
PMID: 34942314.

Abstract

Aquaporins (AQPs) play critical physiological roles in water balance in the central nervous system (CNS). Aquaporin-4 (AQP4), the principal aquaporin expressed in the CNS, has been implicated in the processing of sensory and pain transmission. Akt signaling is also involved in pain mediation, such as neuroinflammatory pain and bone cancer pain. Previously, we found that expression of AQP4 and p-Akt was altered in the rat spinal cord after spinal nerve ligation (SNL). Here, we further investigated the effects of the AQP4 and Akt pathways in the spinal dorsal horn (SDH) on the pathogenesis of neuropathic pain (NP). Spinal AQP4 was significantly upregulated after SNL and was primarily expressed in astrocytes in the SDH. Inhibition of AQP4 with TGN-020 attenuated the development and maintenance of NP by inhibiting glial activation and anti-neuroinflammatory mechanisms. Moreover, inhibition of AQP4 suppressed astrocyte activation both in the SDH and in primary cultures.Similar to AQP4, we found that p-Akt was also significantly elevated after SNL. Inhibition of Akt with MK2206 suppressed AQP4 upregulation and astrocyte activation both in vivo and in vitro. Furthermore, Akt blockade with MK2206 alleviated neuropathic pain in the early and late phases after SNL. These results elucidate the mechanisms involved in the roles of Akt/Aquaporin-4 signaling in the development and maintenance of NP. AQP4 is likely to be a novel therapeutic target for neuropathic pain management.