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The 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. Immunohistochemical 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 nonpeptide (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-induced cutaneous inflammation in rats.

Bcl-2 and Bax have recently been identified as putative repressor and effector proteins respectively, in the cell death program of growth factor-deprived haematopoietic cell lines. Overexpression of bcl-2 in neuronal cell culture prevents apoptosis induced by removal of neurotrophic factors. In the present in vivo study the expression of bcl-2 and bax mRNA has been investigated in dorsal root ganglia of young and adult rats using polymerase chain reaction. A high constitutive expression was observed for both genes in control ganglia. Unilateral transection of the sciatic nerve led to a dramatic decrease in bcl-2 mRNA levels in ganglia of young animals within 5 days following nerve lesion and a partial recovery thereafter. In contrast, the decline in bcl-2 mRNA was much less pronounced in axotomized ganglia of adults. The amount of bax transcripts did not change significantly in ganglia of both young and adult rats up to 20 days after nerve injury. The decrease in bcl-2 expression in dorsal root ganglia may be part of the molecular mechanism leading to neuronal cell death after axotomy-induced deprivation of neurotrophic factors. The age-dependent decline in the ratio of bcl-2 to bax gene products may explain the greater susceptibility of immature neurons to apoptosis.