AbstractThe possible involvement of substance P released from primary afferents in rat skin was investigated in cutaneous inflammation following ultraviolet (UV) irradiation. Recordings from c‐fibres innervating the UV‐exposed hindpaw skin showed long‐lasting low‐frequency (0.8–1.25 Hz) spontaneous activity. Spontaneously active c‐fibres increased to constitute 35.3 of the total population 72 h after UV exposure. Immunohisto‐chemical analysis of substance P‐containing nerve fibres in hindpaw skin revealed a significant increase in substance P immunoreactivity 24 h after UV irradiation. Average length of substance P‐immunolabelled nerve fibres was about two times higher in UV‐exposed compared to control skin. UV‐induced oedema was investigated in rat ears using an ear‐swelling test. Intradermal injection of either peptide (Spantide) or non‐peptide (CP‐96,345) substance P antagonists and epicutaneous application of CP‐96,345 reduced UV‐induced oedema significantly in the late phase of sunburn (>12 h after UV exposure). The UV‐induced increase in skin blood flow was investigated in hindpaw skin up to 72 h by the laser Doppler technique. Epicutaneous application of CP‐96,345 reduced erythema significantly between 12 and 72 h after UV exposure. Thus, our findings suggest the involvement of neurogenic substance P as a proinflammatory mediator in the late phase of UV‐i
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