Pain
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Persistent pain after resolution of clinically appreciable signs of arthritis poses a therapeutic challenge, and immunosuppressive therapies do not meet this medical need. To investigate this conversion to persistent pain, we utilized the K/BxN serum transfer arthritis model, which has persistent mechanical hypersensitivity despite the resolution of visible inflammation. Toll-like receptor (TLR) 4 has been implicated as a potential therapeutic target in neuropathic and other pain models. ⋯ WT arthritic mice had reduced spinal levels of the anti-inflammatory prostaglandin 15-deoxy-Δ(12,14)-PGJ(2) (15d-PGJ(2)) on day 6, compared to IT LPS-RS-treated mice. Direct IT application of 15d-PGJ(2) (0.5 μg) on day 6 improved mechanical hypersensitivity in arthritic mice within 15 min. Hence, TLR4 signaling altered spinal bioactive lipid profiles in the serum transfer model and played a critical role in the transition from acute to chronic postinflammatory mechanical hypersensitivity.
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Cutaneous inflammation induced by ultraviolet (UV) irradiation in the UV-B range has received significant recent interest as a translational inflammatory pain model. Changes in thermal and mechanical sensitivities in the area of primary hyperalgesia are well documented in both the rat and human UV-B models, but the occurrence of secondary mechanical hyperalgesia is controversial. We investigated the occurrence of secondary mechanical hyperalgesia in the rat UV-B model. ⋯ Heat rekindling also induced a significant mechanical hyperalgesia and allodynia on the contralateral hind paw, further suggesting the contribution of central sensitisation. Our data provide strong evidence for a central contribution in both the rat UV-B pain model and an enhanced contribution in the new model combining UV-B irradiation with heat rekindling. We also elucidate potential differences in the methods used by ourselves and others to obtain mechanical withdrawal thresholds in rats, which may explain the lack of secondary hyperalgesia in the rat UV-B model.