Open AccessMultitarget nociceptor sensitization by a promiscuous peptide from the venom of the King Baboon spider
Author(s) -
Rocio K. FinolUrdaneta,
Rebekah Ziegman,
Zoltan Dekan,
Jeffrey R. McArthur,
Stewart Heitmann,
Karen Luna-Ramírez,
Han Shen Tae,
Alexander Mueller,
Hana Starobova,
Yanni K.Y. Chin,
Joshua S. Wingerd,
Eivind A. B. Undheim,
Ben Cristofori-Armstrong,
Adam P. Hill,
Volker Herzig,
Glenn F. King,
Irina Vetter,
Lachlan D. Rash,
David J. Adams,
Paul F. Alewood
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2110932119
Subject(s) - venom , envenomation , nociceptor , sensitization , pharmacology , sodium channel , tetrodotoxin , allodynia , hyperalgesia , biology , chemistry , neuroscience , nociception , biophysics , biochemistry , receptor , sodium , organic chemistry
Significance Pain development and discomfort are universal features of spider envenomation, yet severe pain arising from bites by Old World spiders is poorly understood. Molecular analyses of the venom of the King Baboon spider revealed abundant expression of the inhibitory cystine knot peptide Pm1a. Synthetic Pm1a induces pain in mice while simultaneously enhancing proexcitatory sodium currents and decreasing inhibitory potassium currents. These concomitant effects promote hyperexcitability in pain-sensing neurons that can be reversed by pharmacological inhibition of voltage-gated sodium channels. The coordinated modulation of excitatory and inhibitory ion channels involved in pain propagation may represent an economical and effective defense strategy in pain-inducing defensive venoms.