PMID- 37774485
OWN - NLM
STAT- MEDLINE
DCOM- 20231101
LR  - 20231101
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 124
IP  - Pt B
DP  - 2023 Nov
TI  - Peroxisome proliferator-activated receptor gamma agonist pioglitazone alleviates 
      hemorrhage-induced thalamic pain and neuroinflammation.
PG  - 110991
LID - S1567-5769(23)01316-4 [pii]
LID - 10.1016/j.intimp.2023.110991 [doi]
AB  - BACKGROUND: Thalamic pain frequently occurs after stroke and is a challenging 
      clinical issue. However, the mechanisms underlying thalamic pain remain unclear. 
      Neuroinflammation is a key determining factor in the occurrence and maintenance 
      of hemorrhage-induced thalamic pain. Pioglitazone is an agonist of peroxisome 
      proliferator-activated receptor gamma (PPARgamma) and shows anti-inflammatory effects 
      in multiple diseases. The present work focused on exploring whether PPARgamma is 
      related to hemorrhage-induced thalamic pain. METHODS: Immunostaining was 
      conducted to analyze the cellular localization of PPARgamma and co-localization was 
      evaluated with NeuN, ionized calcium-binding adapter molecular 1 (IBA1), and glia 
      fibrillary acidic protein (GFAP). Western blot analyses were used to evaluate 
      MyD88, pNF-kappaB/NF-kappaB, pSTAT6/STAT6, IL-1beta, TNF-alpha, iNOS, Arg-1, IL-4, IL-6, and 
      IL-10 expression. Behavioral tests in mice were conducted to evaluate continuous 
      pain hypersensitivity. RESULTS: We found that pioglitazone appeared to mitigate 
      the contralateral hemorrhage-induced thalamic pain while inhibiting inflammatory 
      responses. Additionally, Pioglitazone induced phosphorylation of STAT6 and 
      suppressed the phosphorylation NF-kappaB in our model of thalamic pain. These effects 
      could be partially reversed with the PPARgamma antagonist GW9662. CONCLUSION: The 
      PPARgamma agonist pioglitazone can mitigate mechanical allodynia by suppressing the 
      NF-kappaB inflammasome while activating the STAT6 signal pathway, which are 
      well-known to be associated with inflammation.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Li, Da
AU  - Li D
AD  - Department of Anesthesiology, Pain and Perioperative Medicine, the First 
      Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, People's 
      Republic of China; Henan Province International Joint Laboratory of Pain, 
      Cognition and Emotion, the First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou 450052, Henan, People's Republic of China.
FAU - He, Long
AU  - He L
AD  - Department of Anesthesiology, Pain and Perioperative Medicine, the First 
      Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, People's 
      Republic of China; Henan Province International Joint Laboratory of Pain, 
      Cognition and Emotion, the First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou 450052, Henan, People's Republic of China.
FAU - Yuan, Chang
AU  - Yuan C
AD  - Department of Anesthesiology, Pain and Perioperative Medicine, the First 
      Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, People's 
      Republic of China; Henan Province International Joint Laboratory of Pain, 
      Cognition and Emotion, the First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou 450052, Henan, People's Republic of China.
FAU - Ai, Yanqiu
AU  - Ai Y
AD  - Department of Anesthesiology, Pain and Perioperative Medicine, the First 
      Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, People's 
      Republic of China; Henan Province International Joint Laboratory of Pain, 
      Cognition and Emotion, the First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou 450052, Henan, People's Republic of China. Electronic address: 
      aiyanqiu82@163.com.
FAU - Yang, Jian-Jun
AU  - Yang JJ
AD  - Department of Anesthesiology, Pain and Perioperative Medicine, the First 
      Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, People's 
      Republic of China; Henan Province International Joint Laboratory of Pain, 
      Cognition and Emotion, the First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou 450052, Henan, People's Republic of China. Electronic address: 
      yjyangjj@126.com.
LA  - eng
PT  - Journal Article
DEP - 20230927
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - X4OV71U42S (Pioglitazone)
RN  - 0 (PPAR gamma)
RN  - 0 (Thiazolidinediones)
RN  - 0 (NF-kappa B)
RN  - 0 (PPAR-gamma Agonists)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Pioglitazone/therapeutic use
MH  - *PPAR gamma/metabolism
MH  - *Thiazolidinediones/therapeutic use/pharmacology
MH  - NF-kappa B/metabolism
MH  - Neuroinflammatory Diseases
MH  - PPAR-gamma Agonists
MH  - Hemorrhage
MH  - Pain/drug therapy
OTO - NOTNLM
OT  - Hemorrhage
OT  - NF-kappaB
OT  - PPARgamma
OT  - STAT6
OT  - Thalamic pain
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/09/30 09:42
MHDA- 2023/11/01 12:45
CRDT- 2023/09/29 18:03
PHST- 2023/06/15 00:00 [received]
PHST- 2023/09/05 00:00 [revised]
PHST- 2023/09/22 00:00 [accepted]
PHST- 2023/11/01 12:45 [medline]
PHST- 2023/09/30 09:42 [pubmed]
PHST- 2023/09/29 18:03 [entrez]
AID - S1567-5769(23)01316-4 [pii]
AID - 10.1016/j.intimp.2023.110991 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2023 Nov;124(Pt B):110991. doi: 
      10.1016/j.intimp.2023.110991. Epub 2023 Sep 27.