Scorpion Toxin, BmP01, Induces Pain by Targeting TRPV1 Channel

Abstract

The intense pain induced by scorpion sting is a frequent clinical manifestation. To date, there is no established protocol with significant efficacy to alleviate the pain induced by scorpion envenomation. One of the important reasons is that, little information on pain-inducing compound from scorpion venoms is available. Here, a pain-inducing peptide (BmP01) has been identified and characterized from the venoms of scorpion (Mesobuthus martensii). In an animal model, intraplantar injection of BmP01 in mouse hind paw showed significant acute pain in wild type (WT) mice but not in TRPV1 knock-out (TRPV1 KO) mice during 30 min recording. BmP01 evoked currents in WT dorsal root ganglion (DRG) neurons but had no effect on DRG neurons of TRPV1 KO mice. Furthermore, BmP01 evoked currents on TRPV1-expressed HEK293T cells, but not on HEK293T cells without TRPV1. These results suggest that (1) BmP01 is one of the pain-inducing agents in scorpion venoms; and (2) BmP01 induces pain by acting on TRPV1. To our knowledge, this is the first report about a scorpion toxin that produces pain by targeting TRPV1. Identification of a pain-inducing compound may facilitate treating pain induced by scorpion envenomation.

TRPV1 pore turret dictates distinct DkTx and capsaicin gating

“…In recent years, several TRPV1-modulating animal toxins were characterized (14,46,48). These peptide toxins, including DkTx, were found to bind to the outer pore region of the channel (14,15,46,48). One of these toxins, RhTx, was shown to enhance heat-dependent activation of TRPV1 in nanomolar concentrations (14).…”

“…One of these membrane proteins, the transient receptor potential vanilloid 1 (TRPV1), is a nonselective cation channel activated by several plant and animal toxins, noxious heat, protons, and bioactive lipids such as anandamide and 15-HPETE (6)(7)(8)(9)(10)(11). To date, TRPV1-activating animal toxins have been identified in venoms from centipedes, scorpions, snakes, and spiders (12)(13)(14)(15)(16). However, while the molecular basis of TRPV1 activation by the small molecule phytotoxins capsaicin and resiniferatoxin (RTX) has been extensively studied, the activation mechanism of TRPV1 by peptide animal toxins is not fully understood (17)(18)(19)(20).…”

Kunitz-Type Peptide HCRG21 from the Sea Anemone Heteractis crispa Is a Full Antagonist of the TRPV1 Receptor

“…There are only five venom-derived peptides acting on TRPV1 known up to date. A double-knot toxin DkTx, from the Chinese bird spider Ornithoctonus huwena [48], the toxins VaTx1–VaTx3 from the tarantula Psalmopoeus cambridgei [49], and BmP01 from the scorpion Mesobuthus martensii [50] are agonists, while APHC1–APHC3, from the sea anemone H. crispa , are three partially antagonists of the TRPV1 receptor. [28,30,31].…”

The Latoia consocia Caterpillar Induces Pain by Targeting Nociceptive Ion Channel TRPV1

“…TRPV1 is a polymodal ion channel activated by various stimuli (physical and chemical) such as heat, low pH, capsaicin, voltage, and mechanical force [11]. A number of animal toxins, including RhTx, BmP01, and DkTx evoke a prickling and burning sensation by targeting sensory nerve endings of the TRPV1 channel [12][13][14]. These aspects imply that the TRPV1 channel is an extremely grounded target for the defensive peptide toxins to produce pain by poisonous animals' envenomation.…”