PMID- 30785087
OWN - NLM
STAT- MEDLINE
DCOM- 20190827
LR  - 20230308
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 70
DP  - 2019 May
TI  - Inhibitory effect of valproate sodium on pain behavior in diabetic mice involves 
      suppression of spinal histone deacetylase 1 and inflammatory mediators.
PG  - 16-27
LID - S1567-5769(18)31282-7 [pii]
LID - 10.1016/j.intimp.2019.01.050 [doi]
AB  - Anti-epileptic medications are included in the international guidelines for 
      managing neuropathic pain. Valproate sodium (VPS) was recently described as "the 
      forgotten analgesic" and has been reported to relief pain in various models of 
      neuropathic pain. Some studies reported anti-inflammatory and histone deacetylase 
      1 (HDA1) inhibitory properties for sodium valproate. The aim of the current study 
      was to investigate the modulatory effect of VPS on pain behavior and inflammatory 
      reactions in alloxan-induced diabetic neuropathy focusing on HDA1 inhibition and 
      glia reactivity. 28 Male Swiss albino mice were allocated into four groups, (1) 
      vehicle group, (2) alloxan-diabetic group, (3 & 4) alloxan+VPS (25 or 50 mg/kg) 
      groups. VPS was given daily for 5 weeks by oral gavage. Pain behavior 
      demonstrated increased allodynia (von-Frey filaments) and hyperalgesia (hot-plate 
      test) in alloxan-diabetic mice that was reduced significantly by at least one of 
      VPS doses. Sciatic nerves in diabetic mice showed increased histopathology score, 
      increased silver staining for the nerves-indicating myelopathy- and a decrease in 
      immunostaining for nerve growth factor. Spinal cord of diabetic mice showed 
      greater histopathologic score, increased CD11b and glia fibrillary acidic protein 
      (GFAP) immunostaining than vehicle treated mice. Molecular investigations 
      highlighted greater content of spinal histone deacetylases, tumor necrosis 
      factor-alpha (TNF-alpha) and interlukin-1beta (IL1beta) that were favorably modified by VPS. 
      Overall, the current data confirmed that the pain killing and anti-inflammatory 
      activity of VPS is at least partly mediated through inhibition of spinal HDA1 and 
      glia reactivity. These findings support the view of inviting antiepileptics for 
      treating neuropathies.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Elsherbiny, Nehal M
AU  - Elsherbiny NM
AD  - Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tabuk, 
      Tabuk, Saudi Arabia; Department of Biochemistry, Faculty of Pharmacy, Mansoura 
      University, Mansoura, Egypt.
FAU - Ahmed, Eman
AU  - Ahmed E
AD  - Clinical Pharmacology Department, Faculty of Medicine, Suez Canal University, 
      Ismailia, Egypt.
FAU - Kader, Ghada Abdel
AU  - Kader GA
AD  - Department of Anatomy and Embryology, Faculty of Medicine, Suez Canal University, 
      Ismailia, Egypt.
FAU - Abdel-Mottaleb, Yousra
AU  - Abdel-Mottaleb Y
AD  - Department of Pharmacology, Toxicology & Biochemistry, Faculty of Pharmaceutical 
      Sciences and Pharmaceutical Industries, Future University in Egypt, Cairo, Egypt.
FAU - ElSayed, Mohamed H
AU  - ElSayed MH
AD  - Department of Physiology, Faculty of Medicine, Ain Shams University, Cairo, 
      Egypt.
FAU - Youssef, Amal M
AU  - Youssef AM
AD  - Department of Physiology, College of Medicine, Taibah University, Medinah, Saudi 
      Arabia; Department of Physiology, Faculty of Medicine, Suez Canal University, 
      Ismailia, Egypt.
FAU - Zaitone, Sawsan A
AU  - Zaitone SA
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of 
      Tabuk, Tabuk, Saudi Arabia; Department of Pharmacology and Toxicology, Faculty of 
      Pharmacy, Suez Canal University, Ismailia, Egypt. Electronic address: 
      szaitone@ut.edu.sa.
LA  - eng
PT  - Journal Article
DEP - 20190218
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Analgesics)
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 614OI1Z5WI (Valproic Acid)
RN  - EC 3.5.1.98 (Histone Deacetylase 1)
SB  - IM
EIN - Int Immunopharmacol. 2023 Apr;117:109807. PMID: 36890025
MH  - Analgesics/*therapeutic use
MH  - Animals
MH  - Behavior, Animal
MH  - Cells, Cultured
MH  - Cytokines/metabolism
MH  - Diabetes Complications/chemically induced/*drug therapy
MH  - Disease Models, Animal
MH  - Down-Regulation
MH  - Histone Deacetylase 1/*metabolism
MH  - Humans
MH  - Inflammation Mediators/metabolism
MH  - Male
MH  - Mice
MH  - Neuralgia/chemically induced/*drug therapy
MH  - Neuroglia/*physiology
MH  - Spinal Cord/*metabolism
MH  - Valproic Acid/*therapeutic use
OTO - NOTNLM
OT  - Alloxan diabetic neuropathy
OT  - Glia reactivity
OT  - Histone deacetylase
OT  - Mouse
OT  - Valproate sodium
EDAT- 2019/02/21 06:00
MHDA- 2019/08/28 06:00
CRDT- 2019/02/21 06:00
PHST- 2018/12/28 00:00 [received]
PHST- 2019/01/23 00:00 [revised]
PHST- 2019/01/30 00:00 [accepted]
PHST- 2019/02/21 06:00 [pubmed]
PHST- 2019/08/28 06:00 [medline]
PHST- 2019/02/21 06:00 [entrez]
AID - S1567-5769(18)31282-7 [pii]
AID - 10.1016/j.intimp.2019.01.050 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2019 May;70:16-27. doi: 10.1016/j.intimp.2019.01.050. Epub 
      2019 Feb 18.