Reversal of TRESK Downregulation Alleviates Neuropathic Pain by Inhibiting Activation of Gliocytes in the Spinal Cord.
Despite the consensus that activation of TWIK-related spinal cord K+(TRESK) might contribute to the pathogenesis of chronic pain, the specific mechanisms underlying the transfer and development of pain signals still remain obscure. In the present study, we validated that TRESK was expressed in neurons instead of glial cells. Furthermore, in the SNI model of neuropathic pain (NP), downregulation of TRESK in spinal cord neurons resulted in upregulation of connexin 36 (Cx36) and connexin 43 (Cx43), both being subtypes of gap junctions in the spinal cord, with gliocytes in the spinal cord activated ultimately. Compared with SNI rats, intrathecal injection of TRESK gene recombinant adenovirus significantly downregulated the expression levels of Cx36 and Cx43 and suppressed the activation of gliocytes in the spinal cord, with hyperalgesia significantly reduced. In conclusion, TRESK contributes to the pathogenesis of NP by upregulation of synaptic transmission and activation of gliocytes.
Department of Anesthesiology, First People's Hospital of Foshan, Foshan, Guangdong Province, 528000, China.
Jun
J
Zhou
Department of Anesthesiology, Eighth People's Hospital of Guangzhou, Guangzhou, Guangdong Province, 510060, China. gz8hcht@126.com.
Hongtao
H
Chen
Department of Anesthesiology, First People's Hospital of Foshan, Foshan, Guangdong Province, 528000, China.
Chengxiang
C
Yang
Department of Anesthesiology, First People's Hospital of Foshan, Foshan, Guangdong Province, 528000, China.
Jiying
J
Zhong
Department of Anesthesiology, First People's Hospital of Foshan, Foshan, Guangdong Province, 528000, China.
Wanyou
W
He
Department of Anesthesiology, First People's Hospital of Foshan, Foshan, Guangdong Province, 528000, China.
Qingming
Q
Xiong
D000256:Adenoviridae; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D007278:Injections, Spinal; D008297:Male; D009437:Neuralgia / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015221:Potassium Channels / Q000008:administration & dosage / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
C546314:Kcnk18 protein, rat; D015221:Potassium Channels
Gap junction; Gliocyte; Neuropathic pain; Spinal cord; TRESK