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A tarantula peptide against pain via ASIC1a channels and opioid mechanisms

Abstract

Psalmotoxin 1, a peptide extracted from the South American tarantula Psalmopoeus cambridgei, has very potent analgesic properties against thermal, mechanical, chemical, inflammatory and neuropathic pain in rodents. It exerts its action by blocking acid-sensing ion channel 1a, and this blockade results in an activation of the endogenous enkephalin pathway. The analgesic properties of the peptide are suppressed by antagonists of the μ and δ-opioid receptors and are lost in Penk1−/− mice.

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Figure 1: PcTx1, ASIC 1a knockdown and acute pain.
Figure 2: PcTx1 and neuropathic pain.
Figure 3: Opioid receptors and enkephalins are involved in the antinociceptive effect of PcTx1.

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Acknowledgements

We are very grateful to M. Jodar and Y. Benhamou for expert technical assistance and to A. Patel for the reading of the manuscript. This work was supported by the CNRS, the Agence Nationale de la Recherche (Projet Analgésie et canaux Ioniques dans les voies Nociceptives), the Paul Hamel Institute and the Association Française contre les Myopathies.

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Authors and Affiliations

Authors

Contributions

M.M. and C.H. did the initial observations and conducted a large part of the experiments, analyzed the data and participated to the preparation of the manuscript. A.A., S.D., A.G. and A.E. conducted pain experiments both with PcTx1 and the antisense strategy. A.B. conducted localization and electrophysiological experiments and helped in the preparation of the manuscript. P.E. produced and provided PcTx1. N.V. was responsible for the localization and colocalization experiments. N.B. was associated with experiments using opiate antagonists. A.C. measured met-enkephalin concentrations in the cerebrospinal fluid. A.Z. and A.M.Z. provided the Enk−/−, Dyn−/− and Tac1−/− mice. M.L. supervised the project and wrote the manuscript.

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Correspondence to Michel Lazdunski.

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The authors declare no competing financial interests.

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Supplementary Figures 1–7, Results, Methods (PDF 3618 kb)

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Mazzuca, M., Heurteaux, C., Alloui, A. et al. A tarantula peptide against pain via ASIC1a channels and opioid mechanisms. Nat Neurosci 10, 943–945 (2007). https://doi.org/10.1038/nn1940

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