Venoms peptides have produced exceptional sources for
drug development to treat
pain. In this study we examined the antinociceptive and side effects of Tx3-3, a
peptide toxin isolated from Phoneutria nigriventer
venom, which inhibits high-
voltage-dependent calcium channels (
VDCC), preferentially P/Q and
R-type VDCC. We tested the effects of Tx3-3 in animal models of nociceptive (tail-flick test), neuropathic (partial sciatic nerve
ligation and
streptozotocin-induced
diabetic neuropathy), and inflammatory (intraplantar complete
Freund's adjuvant)
pain. In the tail-flick test, both intrathecal (i.t.) and intracerebroventricular (i.c.v.) injection of Tx3-3 in mice caused a short-lasting effect (ED(50) and 95% confidence intervals of 8.8 [4.1-18.8] and 3.7 [1.6-8.4] pmol/site for i.t. and i.c.v. injection, respectively), without impairing motor functions, at least at doses 10-30 times higher than the effective dose. By comparison, ω-
conotoxin MVIIC, a P/Q and
N-type VDCC blocker derived from Conus magus
venom, caused significant motor impairment at doses close to efficacious dose in tail flick test. Tx3-3 showed a long-lasting antinociceptive effect in
neuropathic pain models.
Intrathecal injection of Tx3-3 (30 pmol/site) decreased both
mechanical allodynia produced by sciatic nerve injury in mice and
streptozotocin-induced
allodynia in mice and rats. On the other hand, i.t. injection of Tx3-3 did not alter inflammatory
pain. Taken together, our data show that Tx3-3 shows prevalent antinociceptive effects in the
neuropathic pain models and does not cause adverse motor effects at antinociceptive efficacious doses, suggesting that this
peptide toxin holds promise as a novel therapeutic agent for the control of
neuropathic pain. The Brazilian armed spider Tx3-3, a new P/Q and
R-type calcium channel blocker, effectively alleviates
allodynia in animal
neuropathic pain models.