Article open access publication

A Novel Toxin from Haplopelma lividum Selectively Inhibits the NaV1.8 Channel and Possesses Potent Analgesic Efficacy

Toxins, MDPI, ISSN 2072-6651

Volume 9, 1, 2016

DOI:10.3390/toxins9010007, Dimensions: pub.1039398974, PMC: PMC5308240, PMID: 28035974,

Authors

Meng, Ping (1) (2)
Huang, Honggang (3) (4)
Wang, Gan (5)
Yang, Shilong (1) (2)
Lu, Qiuming (1) (2)
Lai, Ren (1) (2)

Affiliations

Organisations

  1. (1) Chinese Academy of Sciences, grid.9227.e
  2. (2) Kunming Institute of Zoology, grid.419010.d
  3. (3) Danish Diabetes Academy, grid.484078.7
  4. (4) University of Southern Denmark, grid.10825.3e, SDU
  5. (5) Nanjing Agricultural University, grid.27871.3b
  6. (6) Hebei Normal University, grid.256884.5

Countries

China

Denmark

Continents

Asia

Europe

Description

Spider venoms are a complex mixture of peptides with a large number of neurotoxins targeting ion channels. Although thousands of peptide toxins have been identified from venoms of numerous species of spiders, many unknown species urgently need to be investigated. In this study, a novel sodium channel inhibitor, µ-TRTX-Hl1a, was identified from the venom of Haplopelma lividum. It contained eight cysteines and formed a conserved cysteine pattern of ICK motif. µ-TRTX-Hl1a inhibited the TTX-resistant (TTX-r) sodium channel current rather than the TTX-sensitive (TTX-s) sodium channel current. Meanwhile, µ-TRTX-Hl1a selectively inhibited NaV1.8 with an IC50 value of 2.19 μM. Intraperitoneal injection of µ-TRTX-Hl1a dose-dependently reduced inflammatory and neuropathic pain in rodent models of formalin-induced paw licking, tail-flicking, acetic acid-induced writhing, and hot plate test. It showed a better analgesic effect than morphine in inflammatory pain and equipotent effect to morphine in neuropathic pain. These findings demonstrate that µ-TRTX-Hl1a might be a valuable tool for physiology studies on NaV1.8 and a promising lead molecule for pain therapeutics.

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University of Southern Denmark

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Times Cited: 8

Field Citation Ratio (FCR): 2.43

Relative Citation ratio (RCR): 0.55

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