Antinociceptive effect of a novel armed spider peptide Tx3-5 in pathological pain models in mice

Pflugers Arch. 2016 May;468(5):881-94. doi: 10.1007/s00424-016-1801-1. Epub 2016 Feb 22.


The venom of the Brazilian armed spider Phoneutria nigriventer is a rich source of biologically active peptides that have potential as analgesic drugs. In this study, we investigated the analgesic and adverse effects of peptide 3-5 (Tx3-5), purified from P. nigriventer venom, in several mouse models of pain. Tx3-5 was administered by intrathecal injection to mice selected as models of postoperative (plantar incision), neuropathic (partial sciatic nerve ligation) and cancer-related pain (inoculation with melanoma cells) in animals that were either sensitive or tolerant to morphine. Intrathecal administration of Tx3-5 (3-300 fmol/site) in mice could either prevent or reverse postoperative nociception, with a 50 % inhibitory dose (ID50) of 16.6 (3.2-87.2) fmol/site and a maximum inhibition of 87 ± 10 % at a dose of 30 fmol/site. Its effect was prevented by the selective activator of L-type calcium channel Bay-K8644 (10 μg/site). Tx3-5 (30 fmol/site) also produced a partial antinociceptive effect in a neuropathic pain model (inhibition of 67 ± 10 %). Additionally, treatment with Tx3-5 (30 fmol/site) nearly abolished cancer-related nociception with similar efficacy in both morphine-sensitive and morphine-tolerant mice (96 ± 7 and 100 % inhibition, respectively). Notably, Tx3-5 did not produce visible adverse effects at doses that produced antinociception and presented a TD50 of 1125 (893-1418) fmol/site. Finally, Tx3-5 did not alter the normal mechanical or thermal sensitivity of the animals or cause immunogenicity. Our results suggest that Tx3-5 is a strong drug candidate for the treatment of painful conditions.

Keywords: Cancer-related pain; Hyperalgesia; L-type VSCC blocker; Morphine tolerance; Neuropathic pain; Phoneutria nigriventer; Postoperative pain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / adverse effects
  • Analgesics / pharmacology
  • Analgesics / therapeutic use*
  • Animals
  • Calcium Channel Agonists / pharmacology
  • Cancer Pain / drug therapy*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neuralgia / drug therapy*
  • Neuropeptides / adverse effects
  • Neuropeptides / pharmacology
  • Neuropeptides / therapeutic use*
  • Neurotoxins / adverse effects
  • Neurotoxins / pharmacology
  • Neurotoxins / therapeutic use*
  • Nociception / drug effects
  • Spider Venoms / adverse effects
  • Spider Venoms / pharmacology
  • Spider Venoms / therapeutic use*


  • Analgesics
  • Calcium Channel Agonists
  • Neuropeptides
  • Neurotoxins
  • Spider Venoms
  • Tx3 neurotoxin