ArticleThe Journal of international medical research2025
Homer1a inhibits caspase-6 signaling to attenuate inflammatory pain in the spinal dorsal horn.
Article in The Journal of international medical research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
ObjectiveThis study aimed to investigate the effect of Homer1a on caspase-6/tumor necrosis factor-alpha signaling pathway in an inflammatory pain model. We sought to determine whether Homer1a could alleviate nociceptive hypersensitivity by inhibiting the activation of the caspase-6/tumor necrosis factor-alpha signaling pathway.MethodsAn inflammatory pain model was established by unilateral plantar injection of carrageenan in rats. The hypothesis was tested using behavioral and immunological approaches.ResultsIn rats with carrageenan-induced hind paw inflammation, pain hypersensitivity was exacerbated, accompanied by an upregulation of Homer1a and activation of the caspase-6/tumor necrosis factor-alpha signaling pathway. Intrathecal administration of the caspase-6 inhibitor Z-valine-glutamic acid-isoleucine-aspartic acid-fluoromethyl ketone significantly attenuated microglial activation, tumor necrosis factor-alpha release, and thermal hypersensitivity but had no effect on Homer1a expression. Lentiviral overexpression of Homer1a reduced pain hypersensitivity and concurrently inhibited the caspase-6/tumor necrosis factor-alpha signaling pathway.ConclusionsThe present study demonstrates that Homer1a activation suppresses the caspase-6/tumor necrosis factor-alpha signaling pathway and alleviates thermal hypersensitivity in a rat model of inflammatory pain. These findings suggest that the Homer1a/caspase-6 signaling axis may represent a promising therapeutic target for inflammatory pain management.
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