PMID- 37377340
OWN - NLM
STAT- MEDLINE
DCOM- 20230721
LR  - 20230721
IS  - 1948-7193 (Electronic)
IS  - 1948-7193 (Linking)
VI  - 14
IP  - 14
DP  - 2023 Jul 19
TI  - Blocking Pannexin-1 Channels Alleviates Thalamic Hemorrhage-Induced Pain and 
      Inflammatory Depolarization of Microglia in Mice.
PG  - 2548-2559
LID - 10.1021/acschemneuro.3c00217 [doi]
AB  - Central post-stroke pain (CPSP) is a neuropathic pain syndrome that frequently 
      occurs following cerebral stroke. The pathogenesis of CPSP is mainly due to 
      thalamic injury caused by ischemia and hemorrhage. However, its underlying 
      mechanism is far from clear. In the present study, a thalamic hemorrhage (TH) 
      model was established in young male mice by microinjection of 0.075 U of type IV 
      collagenase into the unilateral ventral posterior lateral nucleus and ventral 
      posterior medial nucleus of the thalamus. We found that TH led to microglial 
      pannexin (Panx)-1, a large-pore ion channel, opening within the thalamus 
      accompanied with thalamic tissue injury, pain sensitivities, and neurological 
      deficit, which were significantly prevented by either intraperitoneal injection 
      of the Panx1 blocker carbenoxolone or intracerebroventricular perfusion of the 
      inhibitory mimetic peptide 10Panx. However, inhibition of Panx1 has no additive 
      effect on pain sensitivities upon pharmacological depletion of microglia. 
      Mechanistically, we found that carbenoxolone alleviated TH-induced 
      proinflammatory factors transcription, neuronal apoptosis, and neurite 
      disassembly within the thalamus. In summary, we conclude that blocking of 
      microglial Panx1 channels alleviates CPSP and neurological deficit through, at 
      least in part, reducing neural damage mediated by the inflammatory response of 
      thalamic microglia after TH. Targeting Panx1 might be a potential strategy in the 
      treatment of CPSP.
FAU - Bu, Fan
AU  - Bu F
AUID- ORCID: 0000-0002-0051-6037
AD  - Department of Neurology & Psychology, The Fourth Clinical Medical College of 
      Guangzhou University of Chinese Medicine, Shenzhen, Guangdong 518033, China.
FAU - Li, Yuerong
AU  - Li Y
AD  - Department of Neurology & Psychology, The Fourth Clinical Medical College of 
      Guangzhou University of Chinese Medicine, Shenzhen, Guangdong 518033, China.
FAU - Lan, Shiming
AU  - Lan S
AD  - Department of Neurology & Psychology, The Fourth Clinical Medical College of 
      Guangzhou University of Chinese Medicine, Shenzhen, Guangdong 518033, China.
FAU - Yang, Taiqin
AU  - Yang T
AD  - Department of Neurology & Psychology, The Fourth Clinical Medical College of 
      Guangzhou University of Chinese Medicine, Shenzhen, Guangdong 518033, China.
FAU - He, Baokun
AU  - He B
AD  - Laboratory of Molecular Pharmacology and Drug Discovery, Institute of Chinese 
      Materia Medica, The Fourth Clinical Medical College of Guangzhou University of 
      Chinese Medicine, Shenzhen, Guangdong 518033, China.
FAU - Dong, Peng
AU  - Dong P
AD  - Department of Neurosurgery, The Fourth Clinical Medical College of Guangzhou 
      University of Chinese Medicine, Shenzhen, Guangdong 518033, China.
FAU - Shen, Fengyan
AU  - Shen F
AD  - Department of Anesthesiology, The Fourth Clinical Medical College of Guangzhou 
      University of Chinese Medicine, Shenzhen, Guangdong 518033, China.
FAU - Cai, Haobin
AU  - Cai H
AD  - Department of Neurology & Psychology, The Fourth Clinical Medical College of 
      Guangzhou University of Chinese Medicine, Shenzhen, Guangdong 518033, China.
FAU - Lu, Yunwei
AU  - Lu Y
AD  - Department of Neurology & Psychology, The Fourth Clinical Medical College of 
      Guangzhou University of Chinese Medicine, Shenzhen, Guangdong 518033, China.
FAU - Fei, Yong
AU  - Fei Y
AD  - Department of Anesthesia and Pain Medicine, Affiliated Hospital of Jiaxing 
      University, Jiaxing, Zhejiang 314001, China.
FAU - Xu, Longsheng
AU  - Xu L
AD  - Department of Anesthesia and Pain Medicine, Affiliated Hospital of Jiaxing 
      University, Jiaxing, Zhejiang 314001, China.
FAU - Qin, Xiude
AU  - Qin X
AUID- ORCID: 0009-0000-0338-1847
AD  - Department of Neurology & Psychology, The Fourth Clinical Medical College of 
      Guangzhou University of Chinese Medicine, Shenzhen, Guangdong 518033, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230628
PL  - United States
TA  - ACS Chem Neurosci
JT  - ACS chemical neuroscience
JID - 101525337
RN  - MM6384NG73 (Carbenoxolone)
RN  - 0 (Panx1 protein, mouse)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Connexins)
SB  - IM
MH  - Mice
MH  - Male
MH  - Animals
MH  - Microglia
MH  - Carbenoxolone/adverse effects
MH  - Cerebral Hemorrhage/complications/drug therapy/chemically induced
MH  - *Stroke
MH  - *Neuralgia/drug therapy
MH  - Nerve Tissue Proteins
MH  - Connexins/pharmacology
OTO - NOTNLM
OT  - Panx1
OT  - central post-stroke pain
OT  - microglia
OT  - stroke
OT  - thalamic hemorrhage
EDAT- 2023/06/28 13:09
MHDA- 2023/07/21 06:44
CRDT- 2023/06/28 08:23
PHST- 2023/07/21 06:44 [medline]
PHST- 2023/06/28 13:09 [pubmed]
PHST- 2023/06/28 08:23 [entrez]
AID - 10.1021/acschemneuro.3c00217 [doi]
PST - ppublish
SO  - ACS Chem Neurosci. 2023 Jul 19;14(14):2548-2559. doi: 
      10.1021/acschemneuro.3c00217. Epub 2023 Jun 28.