Analgesic effect of duloxetine on an animal model of monosodium iodoacetate-induced hip osteoarthritis

Authors: 
Kawarai Y, Orita S, Nakamura J, Miyamoto S, Suzuki M, Inage K, Hagiwara S, Suzuki T, Nakajima T, Akazawa T, Ohtori S.
J Orthop Res. 2019 Sep 20. doi: 10.1002/jor.24480.

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. This article is protected by copyright. All rights reserved.

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