A tarantula spider toxin, GsMTx4, reduces mechanical and neuropathic pain

Seung Pyo Park, Byung Moon Kim, Jae Yeon Koo, Hawon Cho, Chang Hoon Lee, Misook Kim, Heung Sik Na, Uhtaek Oh

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Mechanosensitive channels mediate various physiological functions including somatic sensation or pain. One of the peptide toxins isolated from the venom of the Chilean rose tarantula spider (Grammostola spatulata), mechanotoxin 4 (GsMTx4) is known to block stretch-activated cation channels. Since mechanosensitive channels in sensory neurons are thought to be molecular sensors for mechanotransduction, i.e., for touch, pressure, proprioception, and pain, we considered that the venom might block some types of mechanical pain. In order to prepare sufficiently large amounts of GsMTx4 for in vivo nociceptive behavioral tests, we constructed recombinant peptide of GsMTx4. Because the amino-acid sequence of the toxin, but not the nucleotide sequence, is known, we back-translated its amino-acid sequence to nucleotide sequence of yeast codons, constructed a template DNA, subcloned this into a Pichia pastoris expression vector, and purified the recombinant peptide. Intraperitoneal injection of the recombinant GsMTx4 to rats significantly increased the mechanical threshold for paw withdrawal in Randall Sellito test, eliciting significant analgesic responses to inflammation-induced mechanical hyperalgesia. GsMTx4 also reduced mechanical allodynia induced by inflammation and by sciatic nerve injury in Von Frey test. However, the venom was ineffective at changing withdrawal latency in hot plate and tail-flick tests. These results suggest that GsMTx4 selectively alleviates mechanical hyperalgesia, which it presumably achieves by blocking mechanosensitive channels. Because the peptide venom induces analgesia for some forms of mechanical pain, GsMTx4 appears to have potential clinical use as a pain treatment.

Original languageEnglish
Pages (from-to)208-217
Number of pages10
JournalPain
Volume137
Issue number1
DOIs
Publication statusPublished - 2008 Jun 30

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Keywords

  • GsMTx4
  • Mechanical pain
  • Neuropathic pain
  • Spider toxin
  • Tarantula

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Neurology
  • Neuroscience(all)
  • Pharmacology
  • Clinical Psychology

Cite this

Park, S. P., Kim, B. M., Koo, J. Y., Cho, H., Lee, C. H., Kim, M., Na, H. S., & Oh, U. (2008). A tarantula spider toxin, GsMTx4, reduces mechanical and neuropathic pain. Pain, 137(1), 208-217. https://doi.org/10.1016/j.pain.2008.02.013