Inhibition of neuropeptide degradation suppresses sweating but increases the area of the axon reflex flare

Abstract

The neuropeptides CGRP (calcitonin gene-elated peptide) and substance P (SP) mediate neurogenic inflammation. Both are degraded by the neutral endopeptidase (NEP) which can be blocked by phosphoramidon. The aim was to evaluate the effect of NEP inhibition on sweating and vasodilatation. Dermal microdialysis was performed on the skin of 39 subjects. Two fibres were perfused with phosphoramidon (0.01%, 0.02% or 0.2%), two with saline. Acetylcholine (ACh) was either added to the microdialysis perfusate (n = 30, 10 À2 M) or thermoregulatory sweating was induced (n = 9). Co-application of phosphoramidon reduced cholinergic and thermoregulatory sweating. However, the flare size -a localized increase in superficial blood flow after ACh-application -was significantly increased. The increase in flare size is most probably due to increased CGRP levels. The inhibition of sweating by phosphoramidon may involve an increase in SP, a reduction in CGRP-degradation fragments or a direct inhibitory action of phosphoramidon.

Interaction of calcitonin gene related peptide (CGRP) and substance P (SP) in human skin

“…CGRP competes with SP for degradation, which has been shown for NEP (Saleh et al, 1996) leading to increased SP availability. Beyond, more interactions like inhibitory function of CGRP fragments on cleaving enzymes or direct interaction of fragments with NK1 receptors are possible (Schlereth et al, 2013).…”

Sweating chloride bullets: understanding the role of calcium in eccrine sweat glands and possible implications for hyperhidrosis

“…This, in theory, could lead to increases in production of primary fluid. Alternately, it is possible that sudorific modulators such as galanin and CGRP , which appear to accentuate sweat formation once transport is initiated, may now be more functionally important due to this increased basal Cl − secretion.…”

Ciguatoxins Evoke Potent CGRP Release by Activation of Voltage-Gated Sodium Channel Subtypes NaV1.9, NaV1.7 and NaV1.1

“…Furthermore, we found P-CTX-1 to belong to the most potent compounds to induce a long-lasting axon reflex flare in human skin at a concentration as low as 1 nM. The flare was accompanied by a slowly fading burning pain and followed by transient cold allodynia located in the area of the intracutaneous injection and it occurred most likely due to the potent capacity of P-CTX-1 to induce release of CGRP [ 7 , 8 ].…”