Analgesic Effect of Duloxetine on an Animal Model of Monosodium Iodoacetate-Induced Hip Osteoarthritis.
Analgesics
/ pharmacology
Animals
Calcitonin Gene-Related Peptide
/ metabolism
Disease Models, Animal
Drug Evaluation, Preclinical
Duloxetine Hydrochloride
/ pharmacology
Ganglia, Spinal
/ drug effects
Hip Joint
/ diagnostic imaging
Iodoacetic Acid
Male
Osteoarthritis, Hip
/ chemically induced
Rats, Sprague-Dawley
Spinal Cord Dorsal Horn
/ drug effects
descending pain modulatory system
duloxetine
hip osteoarthritis
pain
rat MIA-induced OA model
Journal
Journal of orthopaedic research : official publication of the Orthopaedic Research Society
ISSN: 1554-527X
Titre abrégé: J Orthop Res
Pays: United States
ID NLM: 8404726
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
08
11
2018
accepted:
13
09
2019
pubmed:
21
9
2019
medline:
11
2
2020
entrez:
21
9
2019
Statut:
ppublish
Résumé
We investigated the efficacy of duloxetine on hyperalgesia, histopathological and radiographic findings, pain-related sensory innervation of dorsal-root ganglia (DRG), and spinal changes in a rat model of induced hip osteoarthritis (OA). The right hip joints of male Sprague-Dawley rats (n = 6 rats/group) in the Sham group were injected with 25 μl of sterile saline and 25 μl of sterile saline with 2 mg of monosodium iodoacetate (MIA) were injected to the MIA + Vehicle and MIA + Duloxetine groups. We injected duloxetine 20 mg/kg intraperitoneally in the MIA + Duloxetine group 28 days after injection, whereas rats in the MIA + Vehicle group were injected with 0.5 ml of 20% dimethyl sulfoxide. We assessed hyperalgesia, histopathological changes, immunoreactive (-ir) neurons for calcitonin gene-related peptide and activating transcription factor 3 in DRG, and immunoreactive neurons for ionized-calcium-binding adaptor molecule 1 (Iba1) in the dorsal horn of the spinal cord. MIA administration into the hip joint let to mechanical hyperalgesia of the ipsilateral hind paw (p < 0.05). A single injection of duloxetine significantly attenuated it in induced hip OA (p < 0.05) and suppressed the number of Iba1-ir microglia of the ipsilateral dorsal horn (p < 0.05). These results suggest that a single injection of duloxetine suppressed mechanical hyperalgesia and may influence the expression of Iba1 in the microglia of the ipsilateral dorsal horn in the MIA-induced hip OA. This finding implies the inhibitory effects of duloxetine against neuropathic pain, which may lead to a change of microglial activities. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:422-430, 2020.
Substances chimiques
Analgesics
0
Duloxetine Hydrochloride
9044SC542W
Calcitonin Gene-Related Peptide
JHB2QIZ69Z
Iodoacetic Acid
WF5188V710
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
422-430Informations de copyright
© 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.