PMID- 31234342

OWN - NLM
STAT- PubMed-not-MEDLINE
LR - 20190719
IS - 2077-0383 (Print)
IS - 2077-0383 (Linking)
VI - 8
IP - 6
DP - 2019 Jun 21
TI - Analgesic and Antidepressant Effects of Oltipraz on Neuropathic Pain in Mice
by
Modulating Microglial Activation.
LID - E890 [pii]
LID - 10.3390/jcm8060890 [doi]
AB - Nerve injury provokes microglial activation, contributing to the sensory and
emotional disorders associated with neuropathic pain that do not completely
resolve with treatment. In C57BL/6J mice with neuropathic pain induced by
chronic
constriction of the sciatic nerve (CCI), we evaluated the effects of
oltipraz, an
antioxidant and anticancer compound, on (1) allodynia and hyperalgesia, (2)
microglial activation and pain signaling pathways, (3) oxidative stress, and
(4)
depressive-like behaviors. Twenty-eight days after surgery, we assessed the
effects of oltipraz on the expression of CD11b/c (a microglial marker),
phosphoinositide 3-kinase (PI3K)/ phosphorylated protein kinase B (p-Akt),
nuclear factor-kappaB (NF-kappaB) transcription factor, and mitogen activated
protein kinases (MAPK) in the spinal cord, hippocampus, and prefrontal
cortex.
Our results show that oltipraz alleviates neuropathic pain by inhibiting
microglial activation and PI3K/p-Akt, phosphorylated inhibitor of kappaBalpha
(p-IkappaBalpha), and MAPK overexpression, and by normalizing and/or
enhancing
the expression of antioxidant proteins, nuclear factor erythroid
derived-2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), and
NAD(P)H:quinone
oxidoreductase-1 (NQO1) in the spinal cord. The inhibition of microglial
activation and induction of the Nrf2/HO-1/NQO1 signaling pathway in the
hippocampus and/or prefrontal cortex may explain the antidepressant effects
of
oltipraz during neuropathic pain. These data demonstrate the analgesic and
antidepressant effects of oltipraz and reveal its protective and antioxidant
properties during chronic pain.
FAU - Diaz, Andres Felipe
AU - Diaz AF
AD - Grup de Neurofarmacologia Molecular, Institut d'Investigacio Biomedica Sant
Pau,
Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain.
andresfelipe.diaz@e-campus.uab.cat.
AD - Institut de Neurociencies, Universitat Autonoma de Barcelona, 08193
Barcelona,
Spain. andresfelipe.diaz@e-campus.uab.cat.
FAU - Polo, Sara
AU - Polo S
AD - Grup de Neurofarmacologia Molecular, Institut d'Investigacio Biomedica Sant
Pau,
Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain.
sara.polor@e-campus.uab.cat.
AD - Institut de Neurociencies, Universitat Autonoma de Barcelona, 08193
Barcelona,
Spain. sara.polor@e-campus.uab.cat.
FAU - Gallardo, Nuria
AU - Gallardo N
AD - Grup de Neurofarmacologia Molecular, Institut d'Investigacio Biomedica Sant
Pau,
Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain.
u1934609@campus.udg.edu.
AD - Institut de Neurociencies, Universitat Autonoma de Barcelona, 08193
Barcelona,
Spain. u1934609@campus.udg.edu.
FAU - Leanez, Sergi
AU - Leanez S
AD - Grup de Neurofarmacologia Molecular, Institut d'Investigacio Biomedica Sant
Pau,
Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain.
sergi.leanez@uab.es.
AD - Institut de Neurociencies, Universitat Autonoma de Barcelona, 08193
Barcelona,
Spain. sergi.leanez@uab.es.
FAU - Pol, Olga
AU - Pol O
AUID- ORCID: 0000-0002-4621-8457
AD - Grup de Neurofarmacologia Molecular, Institut d'Investigacio Biomedica Sant
Pau,
Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain.
opol@santpau.es.
AD - Institut de Neurociencies, Universitat Autonoma de Barcelona, 08193
Barcelona,
Spain. opol@santpau.es.
LA - eng
GR - PS0900968/Ministerio de Economia y Competitividad, Instituto de Salud Carlos
III
GR - PI1800645/Ministerio de Ciencia, Innovacion y Universidades, Instituto de
Salud
Carlos III and Fondo Europeo de Desarrollo Regional (FEDER), Union Europea
PT - Journal Article
DEP - 20190621
PL - Switzerland
TA - J Clin Med
JT - Journal of clinical medicine
JID - 101606588
PMC - PMC6616658
OTO - NOTNLM
OT - analgesia
OT - inflammation
OT - microglia
OT - neuropathic pain
OT - oltipraz
OT - oxidative stress
EDAT- 2019/06/27 06:00
MHDA- 2019/06/27 06:01
CRDT- 2019/06/26 06:00
PHST- 2019/05/26 00:00 [received]
PHST- 2019/06/12 00:00 [revised]
PHST- 2019/06/15 00:00 [accepted]
PHST- 2019/06/26 06:00 [entrez]
PHST- 2019/06/27 06:00 [pubmed]
PHST- 2019/06/27 06:01 [medline]
AID - jcm8060890 [pii]
AID - 10.3390/jcm8060890 [doi]
PST - epublish
SO - J Clin Med. 2019 Jun 21;8(6). pii: jcm8060890. doi: 10.3390/jcm8060890.