Biomedical subjects
D Alvares
Publications and source records attributed to D Alvares.
Modelling the prolonged effects of neonatal pain.
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Sensory hyperinnervation after neonatal skin wounding: effect of bupivacaine sciatic nerve block.
The response to tissue injury includes sensitization of peripheral nociceptors and central neuronal pathways leading to acute clinical and inflammatory pain. A further response is sprouting of sensory nerve terminals in the region of skin damage. This hyperinnervation response is particularly intense in neonates compared with adults. In this study, we tested the effect of regional nerve block at the time of injury on skin hyperinnervation. Anaesthetized newborn rat pups were treated with percutaneous sciatic nerve block injections of 0.25% bupivacaine 25 microliters followed by a localized hindpaw skin wound. Cutaneous innervation was studied by image analysis of immunostained skin sections, 7 days after wounding, and sensory thresholds were assessed using von Frey hairs. The results showed that both hyperinnervation and hypersensitivity were not significantly altered by the application of a regional nerve block at the time of injury. This suggests that regional analgesia, used commonly in clinical practice, is unlikely to prevent the hyperinnervation that follows skin wounding.
Neonatally wounded skin induces NGF-independent sensory neurite outgrowth in vitro.
An in vitro model was established to investigate factors underlying the sensory hyperinnervation of neonatal rat skin wounds that has been observed in vivo (Reynolds and Fitzgerald, J. Comp. Neurol. 358 (1995) 487-489). Explants of normal and wounded rat dorsal foot skin were co-cultured with explants of embryonic chick or newborn rat dorsal root ganglia for 24 h and the number of sensory neurites counted. Explants of skin surrounding a wound made at birth were taken 3 (P3) or 10 (P10) days later and compared with normal skin of the same age. In addition, explants were taken from adult skin wounded 3 and 10 days earlier. At P3, normal skin induced weak neurite outgrowth (mean 13.1 +/- 2.1 neurites per ganglion explant) but skin that had been wounded 3 days earlier, at birth, induced three times more neurite outgrowth (37.8 +/- 3.3). Ten days after wounding at birth, neurite outgrowth was still substantial (40.9 +/- 3.3) although at that age (P10), even normal skin stimulates substantial growth (37.4 +/- 2.9). Normal adult skin also stimulated neurite outgrowth (28.7 +/- 0.45) but this was not increased by wounding 3 or 10 days earlier, and this was enhanced 3 days but not 10 days after wounding. Anti-NGF (nerve growth factor) added to the culture medium blocked the constitutive neurite stimulating activity from normal P10 and adult skin but was ineffective in blocking the neurite stimulating activity produced by neonatal wounding. It is concluded that skin wounding at birth results in release of one or more sensory neurotrophic factors that stimulate rat and chick dorsal root ganglia neurite outgrowth for at least 10 days, but which do not include NGF.