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Smoking makes them appear earlier and more pronounced

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Both the tissue-resident macrophages and peripheral nerve macrophages secrete a variety of mediators, such as high mobility group box 1, interleukin 1 (IL-1), and IL-6, that regulate the excitability of primary afferents and neurons and contribute to the pathogenesis of inflammatory and neuropathic pain (Sekiguchi et al., 2018)

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