Chikungunya virus‐induced persistent allodynia is accompanied by joint microenvironmental changes and involves cartilage degradation and TRPA1 activation

Background and purpose Chikungunya virus (CHIKV) causes debilitating chronic joint pain. CHIKV‐induced pain mechanisms are not completely understood and models designed to resemble CHIKV chronic pain are critical for the development of novel therapeutic approaches. Experimental approach Mechanical allodynia was induced by injection of either inactivated CHIKV or its viral RNA into the mouse ipsilateral knee. Both ipsilateral and contralateral joints were collected for histological analysis, collagen Type I content and immunohistochemistry. The effects of paracetamol and sodium diclofenac were assessed and the role of the transient receptor potential ankyrin 1 (TRPA1) was investigated using the antagonist HC‐030031 and TRPA1 knockout (KO) mice. CHIKV‐induced Ca 2+ influx was also assessed in mouse dorsal root ganglion (DRG) neurones. Key results CHIKV or its RNA caused pronounced and time‐dependent bilateral secondary mechanical allodynia. CHIKV caused structural damage in the ipsilateral joint and increased collagen type I content. Higher IL‐10, VEGF and TGF β expressions were observed in the affected joints. Paracetamol or sodium diclofenac reduced allodynia, which was also absent in TRPA1 KO and HC‐030031‐treated mice. TRPA1 expression was up‐regulated in CHIKV‐injected joints whilst CHIKV envelope E2 protein or RNA induced Ca 2+ influx in DRG neurones was antagonized by HC‐030031. Conclusion and implications Insights into CHIKV‐associated pain have been made giving a guide to targeted analgesic strategies. CHIKV or its RNA injection triggers bilateral secondary mechanical allodynia, accompanied by knee joint damage and a TRPA1‐dependent mechanism. Indicating TRPA1 blockers have the potential to be repurposed or further investigated for the clinical management of CHIKV‐associated chronic pain.