Analgesic Effect of Duloxetine on an Animal Model of Monosodium Iodoacetate‐Induced Hip Osteoarthritis

Abstract

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 generelated 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.

Analgesic effects and arthritic changes following tramadol administration in a rat hip osteoarthritis model

“…32,33 Recent studies reported that the rat hip OA model induced by 2.0 mg of MIA exhibits peripheral inflammation, local nerve damage, and central sensitization, thus leading to chronic pain. 13,34,35 Regarding tramadol administration in the MIA model, Rachel et al 14 reported that tramadol administration improved mechanical hypersensitivity in the knee of MIA-induced OA model animals. Ishikawa et al 17 similarly reported that tramadol administration improved the gait paradigm in a rat knee OA model induced by MIA.…”

“…It has also been reported that duloxetine exerts a pain-relieving effect on neuropathic pain in this animal model. 13 Tramadol is a weak opioid that acts on µ-opioid receptors, with a lower affinity for the receptor than morphine. 14 Tramadol is widely recognized and used for relieving pain in OA.…”

Intra-articular injection of monoiodoacetate induces diverse hip osteoarthritis in rats, depending on its dose

“…The histological OARSI scores were 22.7. Thus, the radiographic and histological outcomes were similar [ 11 ]. Our results are consistent with these.…”

“…They reported that, in rats with hip OA induced by 0.5 mg of MIA, OARSI scores were approximately 10 at 4 weeks after induction [ 27 ]. By contrast, another study reported that OARSI scores were almost at maximum 4 weeks after administration of 2 mg of MIA into the hip joint [ 11 ]. These results validate our findings, i.e., more than 2 mg of MIA provoked end-stage OA at 8 weeks after injection.…”

“…The expression of microglia in the spinal cord also increased in this OA model. The systematic administration of serotonin and norepinephrine reuptake inhibitor attenuated hip pain via descending pain modulatory system, which suggested that end-stage OA is associated with both inflammatory and neuropathic pain [ 11 ]. On the other hand, intra-articular administration of 2 mg of MIA provoked relatively strong joint instability, which was different from the gradual OA changes seen in clinical practice.…”