RFa-related peptides are algogenic: evidence in vitro and in vivo

The European Journal of Neuroscience
Yevgen K YudinOleg Krishtal

Abstract

RFamide (RFa)-related peptides modulate pain processing in the mammalian CNS. The effects of these peptides are generally considered as 'anti-opioid'. They also decrease the rate of desensitization of acid-sensing ionic channels (ASICs), putative nociceptors in dorsal root ganglia neurons [C. Askwith et al. (2000) Neuron, 26, 133-141]. We have tested the role of mollusc-derived peptide, FMRFa (Phe-Met-Arg-Phe-amide) and its synthetic analogues in peripheral nociception. Here we demonstrate that RFa-related peptides powerfully excite the majority of C-fibres in the skin-nerve preparation of rat: 76% of 55 tested fibres with the conduction velocity below 2 m/s responded with long-lasting discharges to the application of peptides (20 microm). When injected subcutaneously in vivo (mice), they initiate nociceptive behaviour. We confirm the data on humans [S. Ugawa et al. (2002) J. Clin. Invest., 110, 1185-1190]: the activation of C-fibres by acid is inhibited by channel blocker of ASICs, amiloride. However, there is no correlation in the sensitivity of C-fibres to RFa peptides, protons and amiloride: 74% of tested RFa-sensitive C-fibres were insensitive to protons and in 67% of cases the response to peptides was insensitive to amilo...Continue Reading

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Citations

Jan 19, 2011·ACS Chemical Neuroscience·Wei-Guang Li, Tian-Le Xu
Jul 12, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Viktor LukacsTibor Rohacs
May 30, 2006·Neuroscience Research·Yevgen K YudinOleg A Krishtal
Jan 31, 2006·Peptides·Hsiu-Ying T Yang, Michael J Iadarola
May 1, 2010·Expert Review of Clinical Pharmacology·Jacques NoëlEric Lingueglia
Jul 8, 2011·Neuroreport·Min-Goo LeeBradley J Undem
Feb 6, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Min-Goo LeeBradley J Undem

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