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Scorpion Toxin, BmP01, Induces Pain by Targeting TRPV1 Channel.

Hakim MA, Jiang W, Luo L, Li B, Yang S, Song Y, Lai R - Toxins (Basel) (2015)

Bottom Line: Furthermore, OPEN ACCESS Toxins 2015, 7 3672 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.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China. hakeem.geb.ru@gmail.com.

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, OPEN ACCESS Toxins 2015, 7 3672 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.

No MeSH data available.


Related in: MedlinePlus

Mean duration (±S.E.) of paw licking and electrophysiology on DRG neurons. (A) Different doses of BmP01 along with capsaicin and kaliotoxin were injected into WT mice. Kaliotoxin showed no significant pain behavior, whereas application of 500 µM BmP01 showed acute pain behavior similar to capsaicin; (B) Ten microliters (25 ng/μL) Crude venom injected into WT and TRPV1 KO mice showed the significant difference of the pain behavior between WT and TRPV1 KO mice; (C) Ten microlites saline (control), 500 μM of BmP01, kaliotoxin, capsaicin and 10 μL (25 ng/μL) crude venom were injected into the paw of WT mice. BmP01 and capsaicin induced pain in WT mice. Kaliotoxin was unable to induce pain whereas crude venom induces severe pain; (D) Ten microliters saline (control), 500 μM of BmP01, kaliotoxin, capsaicin and 10 μL (25 ng/μL) crude venom were injected into the paw of TRPV1 KO mice. Similar to capsaicin, BmP01 did not induce pain, while only crude venom induced pain; (E) Both BmP01 (300 μM) and capsaicin (10 μM) evoked the currents on DRG sensory neurons of WT mice. Contrastingly, in DRG neurons from TRPV1 KO mouse, BmP01 as well as capsaicin did not evoke currents; (F) Normalized currents evoked by BmP01 and capsaicin on DRG neurons of WT and TRPV1 KO mice. For both BmP01 and capsaicin, current traced is significantly lower in TRPV1 KO mice than in WT mice. *p < 0.01, n = 10.
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toxins-07-03671-f004: Mean duration (±S.E.) of paw licking and electrophysiology on DRG neurons. (A) Different doses of BmP01 along with capsaicin and kaliotoxin were injected into WT mice. Kaliotoxin showed no significant pain behavior, whereas application of 500 µM BmP01 showed acute pain behavior similar to capsaicin; (B) Ten microliters (25 ng/μL) Crude venom injected into WT and TRPV1 KO mice showed the significant difference of the pain behavior between WT and TRPV1 KO mice; (C) Ten microlites saline (control), 500 μM of BmP01, kaliotoxin, capsaicin and 10 μL (25 ng/μL) crude venom were injected into the paw of WT mice. BmP01 and capsaicin induced pain in WT mice. Kaliotoxin was unable to induce pain whereas crude venom induces severe pain; (D) Ten microliters saline (control), 500 μM of BmP01, kaliotoxin, capsaicin and 10 μL (25 ng/μL) crude venom were injected into the paw of TRPV1 KO mice. Similar to capsaicin, BmP01 did not induce pain, while only crude venom induced pain; (E) Both BmP01 (300 μM) and capsaicin (10 μM) evoked the currents on DRG sensory neurons of WT mice. Contrastingly, in DRG neurons from TRPV1 KO mouse, BmP01 as well as capsaicin did not evoke currents; (F) Normalized currents evoked by BmP01 and capsaicin on DRG neurons of WT and TRPV1 KO mice. For both BmP01 and capsaicin, current traced is significantly lower in TRPV1 KO mice than in WT mice. *p < 0.01, n = 10.

Mentions: We investigated the dose-response of kaliotoxin, capsaicin and BmP01 for pain behavior in WT mice. Capsaicin and BmP01 induced acute pain in a dose dependent manner, whereas well known potassium channel inhibitor kaliotoxin (a potent inhibitor of Kv1.1 and Kv1.3) did not induce pain (Figure 4A). In order to investigate whether TRPV1 is one of the targets of pain inducing toxins from scorpion venom, the effect of crude venom was tested in WT and TRPV1 KO mice. Crude venom (25 ng/µL) was injected into the WT and TRPV1 KO mice and it was noticed that there was a significant difference of pain behavior between WT and TRPV1 KO mice (Figure 4B). To test whether BmP01 produces the pain by going through the TRPV1 pathway, 10 μL BmP01 (500 µM) along with capsaicin (500 µM), kaliotoxin (500 µM) and crude venom (25 ng/µL) were tested to check the pain behavior in WT and TRPV1 KO mice. The same volume of saline was injected for control. The duration of licking/biting represented in bar graph showed that BmP01 and capsaicin induced pain in WT mice (Figure 4C). Whereas, surprisingly, similar to capsaicin, BmP01 lost function to induce pain in TRPV1 KO mice (Figure 4D). These findings suggest that BmP01 may play a role to induce pain in the similar way with capsaicin by targeting TRPV1 channels.


Scorpion Toxin, BmP01, Induces Pain by Targeting TRPV1 Channel.

Hakim MA, Jiang W, Luo L, Li B, Yang S, Song Y, Lai R - Toxins (Basel) (2015)

Mean duration (±S.E.) of paw licking and electrophysiology on DRG neurons. (A) Different doses of BmP01 along with capsaicin and kaliotoxin were injected into WT mice. Kaliotoxin showed no significant pain behavior, whereas application of 500 µM BmP01 showed acute pain behavior similar to capsaicin; (B) Ten microliters (25 ng/μL) Crude venom injected into WT and TRPV1 KO mice showed the significant difference of the pain behavior between WT and TRPV1 KO mice; (C) Ten microlites saline (control), 500 μM of BmP01, kaliotoxin, capsaicin and 10 μL (25 ng/μL) crude venom were injected into the paw of WT mice. BmP01 and capsaicin induced pain in WT mice. Kaliotoxin was unable to induce pain whereas crude venom induces severe pain; (D) Ten microliters saline (control), 500 μM of BmP01, kaliotoxin, capsaicin and 10 μL (25 ng/μL) crude venom were injected into the paw of TRPV1 KO mice. Similar to capsaicin, BmP01 did not induce pain, while only crude venom induced pain; (E) Both BmP01 (300 μM) and capsaicin (10 μM) evoked the currents on DRG sensory neurons of WT mice. Contrastingly, in DRG neurons from TRPV1 KO mouse, BmP01 as well as capsaicin did not evoke currents; (F) Normalized currents evoked by BmP01 and capsaicin on DRG neurons of WT and TRPV1 KO mice. For both BmP01 and capsaicin, current traced is significantly lower in TRPV1 KO mice than in WT mice. *p < 0.01, n = 10.
© Copyright Policy
Related In: Results  -  Collection

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toxins-07-03671-f004: Mean duration (±S.E.) of paw licking and electrophysiology on DRG neurons. (A) Different doses of BmP01 along with capsaicin and kaliotoxin were injected into WT mice. Kaliotoxin showed no significant pain behavior, whereas application of 500 µM BmP01 showed acute pain behavior similar to capsaicin; (B) Ten microliters (25 ng/μL) Crude venom injected into WT and TRPV1 KO mice showed the significant difference of the pain behavior between WT and TRPV1 KO mice; (C) Ten microlites saline (control), 500 μM of BmP01, kaliotoxin, capsaicin and 10 μL (25 ng/μL) crude venom were injected into the paw of WT mice. BmP01 and capsaicin induced pain in WT mice. Kaliotoxin was unable to induce pain whereas crude venom induces severe pain; (D) Ten microliters saline (control), 500 μM of BmP01, kaliotoxin, capsaicin and 10 μL (25 ng/μL) crude venom were injected into the paw of TRPV1 KO mice. Similar to capsaicin, BmP01 did not induce pain, while only crude venom induced pain; (E) Both BmP01 (300 μM) and capsaicin (10 μM) evoked the currents on DRG sensory neurons of WT mice. Contrastingly, in DRG neurons from TRPV1 KO mouse, BmP01 as well as capsaicin did not evoke currents; (F) Normalized currents evoked by BmP01 and capsaicin on DRG neurons of WT and TRPV1 KO mice. For both BmP01 and capsaicin, current traced is significantly lower in TRPV1 KO mice than in WT mice. *p < 0.01, n = 10.
Mentions: We investigated the dose-response of kaliotoxin, capsaicin and BmP01 for pain behavior in WT mice. Capsaicin and BmP01 induced acute pain in a dose dependent manner, whereas well known potassium channel inhibitor kaliotoxin (a potent inhibitor of Kv1.1 and Kv1.3) did not induce pain (Figure 4A). In order to investigate whether TRPV1 is one of the targets of pain inducing toxins from scorpion venom, the effect of crude venom was tested in WT and TRPV1 KO mice. Crude venom (25 ng/µL) was injected into the WT and TRPV1 KO mice and it was noticed that there was a significant difference of pain behavior between WT and TRPV1 KO mice (Figure 4B). To test whether BmP01 produces the pain by going through the TRPV1 pathway, 10 μL BmP01 (500 µM) along with capsaicin (500 µM), kaliotoxin (500 µM) and crude venom (25 ng/µL) were tested to check the pain behavior in WT and TRPV1 KO mice. The same volume of saline was injected for control. The duration of licking/biting represented in bar graph showed that BmP01 and capsaicin induced pain in WT mice (Figure 4C). Whereas, surprisingly, similar to capsaicin, BmP01 lost function to induce pain in TRPV1 KO mice (Figure 4D). These findings suggest that BmP01 may play a role to induce pain in the similar way with capsaicin by targeting TRPV1 channels.

Bottom Line: Furthermore, OPEN ACCESS Toxins 2015, 7 3672 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.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China. hakeem.geb.ru@gmail.com.

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, OPEN ACCESS Toxins 2015, 7 3672 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.

No MeSH data available.


Related in: MedlinePlus