A tarantula spider toxin, GsMTx4, reduces mechanical and neuropathic pain.
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.
Park
Seung Pyo
SP
The Sensory Research Center, Creative Research Initiatives Seoul National University, College of Pharmacy, Kwanak, Shillim 9-dong, Seoul 151-742, Republic of Korea Department of Physiology, College of Medicine, Korea University, 126-1 Anam-dong 5 Ga, Sungbuk, Seoul 136-705, Republic of Korea.
Kim
Byung Moon
BM
Koo
Jae Yeon
JY
Cho
Hawon
H
Lee
Chang Hoon
CH
Kim
Misook
M
Na
Heung Sik
HS
Oh
Uhtaek
U
D000818:Animals; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D009437:Neuralgia / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D010812:Physical Stimulation / Q000009:adverse effects / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D013111:Spider Venoms / Q000494:pharmacology / Q000627:therapeutic use*; D013112:Spiders
D036341:Intercellular Signaling Peptides and Proteins; C411249:MTx4 protein, Grammostola spatulata; D010455:Peptides; D013111:Spider Venoms