Substance P in sensory nerve fibres contributes to the development of oedema in the rat hind paw after thermal injury

Abstract

1 Immersion of the hind paws of anaesthetized rats in hot water for 5 min induced massive plasma protein leakage as indicated by extravasation of Evans blue dye in the skin. The threshold temperature which caused noticeable plasma extravasation was 45°C, a maximal response was obtained between 55°C and 60°C. 2 Pretreatment of rats 2 days after birth with 50mg kg-capsaicin significantly reduced the Evans blue extravasation induced by hot water at 50°C, 55°C and 60°C, whereas guanethidine pretreatment 24 h before the experiment caused a significantly increased response at 40°C, 45°C and 50°C. 3 When Evans blue was injected between 10 and 120 min after immersion of the paw in hot water, a significant extravasation of the dye was no longer detectable. However, the weight of the paw as well as the weight of the piece of skin taken for Evans blue quantification increased during this period indicating the progressive development of oedema in the skin and underlying tissues. 4 In rats treated with capsaicin as neonates, the increase in paw weight after immersion in water of 50°C for 5 min was significantly delayed during the first hour, but there was no difference after two hours.5 In rats pretreated with D-Argt,D-Pro2,D-Trp7'9, Leull-substance P, a substance P (SP) antagonist, the Evans blue extravasation was significantly reduced. However, the response, which remained in rats treated with capsaicin as neonates was not blocked by the SP-antagonist. 6 It is concluded that activation of peripheral branches of sensory SP neurones contributes to the initial massive protein extravasation and to the subsequent rate of development of oedema following heat injury. Release of histamine did not significantly contribute to this response at the lower temperatures, although the response was reduced by histamine receptor blocking drugs at 55°C and 60°C. Decreasing the sympathetic vasoconstrictor tone by guanethidine resulted in an increased response.

Increased Delayed-Type Hypersensitivity Reaction in Rats Neuromanipulated with Capsaicin

“…The neurotoxic effect of capsaicin reduce the neu rogenic inflammatory response to mechanical [22], chemical [23], thermal [24] and immunological stimuli [25]. Local administration of CAPS into human skin has produce effects similar to those reported in this study.…”

Immunohistochemical localization of histamine H3 receptors in rodent skin, dorsal root ganglia, superior cervical ganglia, and spinal cord: Potential antinociceptive targets

“…CGRP and SP, released during tissue damage, produce vasodilation and plasma extravasation (Brain et al, 1992;Brain and Williams, 1989;Lembeck and Holzer, 1979;Saria, 1984), which, in turn, allow the infiltration of additional inflammatory mediators (Bar-Shavit et al, 1980;Hartung et al, 1986;Helme and Andrews, 1985;Payan et al, 1984;Saito et al, 1986). Peptide release also activates mast cells to release histamine (Johnson and Erdos, 1973;.…”

Local secretion of corticotropin-releasing hormone in the joints of Lewis rats with inflammatory arthritis.

“…CRH is also depleted in the rat spinal cord in response to capsaicin ( 19). Much attention has been focused on SP, which can evoke many signs of acute inflammation and inflammatory arthritis, including vasodilation, increased vascular permeability, T lymphocyte proliferation, mast cell degranulation, macrophage activation, granulocyte activation and chemotaxis, fibroblast proliferation, and synoviocyte secretion ofprostaglandin E2 and collagenase ( 14,18,(49)(50)(51)(52)(53)(54). SP-containing nerve terminals have been demonstrated in normal rat synovium but are not detectable in the superficial lining and sublining zones of synovium from adjuvant-arthritic rats (55).…”

“…For example, substance P (SP), which is primarily derived from sensory afferent unmyelinated c fibers, significantly augments the local inflammatory response (13)(14)(15)(16). Many other neuropeptides are present in sensory afferent unmyelinated c and small myelinated A-6 fibers, but their contribution to inflammation remains less well defined.…”