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We investigated the analgesic effects of tramadol and the arthritic changes following tramadol administration in the rat hip osteoarthritis (OA) model using mono‐iodoacetate (MIA). The right hip joints of male Sprague–Dawley rats (n = 5 rats/group) in the Sham group were injected with 25 μl of sterile saline and 1% of fluorogold (FG) retrograde neurotracer. In the MIA + Vehicle and MIA + Tramadol groups, FG and 25 μl of sterile saline with 0.5 mg of MIA were injected into the right hip joint. The MIA + Vehicle and MIA + Tramadol groups were administered daily for 4 weeks, either sterile saline (10 mg/kg, intraperitoneal [i.p.]) or tramadol (10 mg/kg, i.p.). We assessed hyperalgesia every week after MIA administration. Histopathological changes and immunoreactive neurons for calcitonin gene‐related peptide (CGRP) in dorsal root ganglia (DRG) were evaluated after 4 weeks of treatment. MIA injection into the hip joint led to mechanical hyperalgesia (p < 0.01), which was significantly reduced by tramadol administration (p < 0.01). Furthermore, daily i.p injection of tramadol significantly suppressed CGRP expression in DRG (p < 0.0001). MIA + Vehicle and MIA + Tramadol groups showed significant cartilage reduction and degeneration compared to the Sham group (p < 0.0001). Interestingly, OA changes significantly progressed in the MIA + Tramadol group compared to the MIA + Vehicle group (p < 0.0001). [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the local production of proinflammatory cytokines, pain‐related sensory innervation of dorsal‐root ganglia (DRG), and spinal changes in a rat model of induced hip osteoarthritis (OA). Seventy‐five Sprague–Dawley rats were used, including 25 controls and 50 injected into the right hip joints (sham group, injected with 25 µl of sterile saline: N = 25; and monosodium iodoacetate (MIA) group, injected with 25 µl of sterile saline with 2 mg of MIA: N = 25). We measured the local production of TNF‐α, immunoreactive (‐ir) neurons for calcitonin gene‐related peptide (CGRP), and growth associated protein‐43 (GAP‐43) in DRG, and immunoreactive neurons for ionized‐calcium‐binding adaptor molecule‐1 (Iba‐1) in the dorsal horn of spinal cord, on post‐induction days 7, 14, 28, 42, and 56 (N = 5 rats/group/time point). For post‐induction days 7–42, the MIA group presented significantly elevated concentrations of TNF‐α than the other groups (p < 0.01), and a higher expression of CGRP‐ir in FG‐labeled DRG neurons than the sham group (p < 0.01). MIA rats also presented significantly more FG‐labeled GAP‐43‐ir DRG neurons than the sham group on post‐induction days 28, 42, and 56 (p < 0.05), and a significantly higher number of Iba‐1‐ir microglia in the ipsilateral dorsal horn than the other groups, on post‐induction days 28, 42, and 56. The results suggest that in rat models, pain‐related pathologies due to MIA‐induced hip OA, originate from inflammation caused by cytokines, which leads to progressive, chronic neuronal damage that may cause neuropathic pain. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2978–2986, 2018. [ABSTRACT FROM AUTHOR]