Table 1.

Key toxin features and interactions with TRPV1.

Species	Toxin
Chinese earth tiger tarantula Chilobrachys guangxiensis	Double-knot toxin (DkTx) [36]	Key Amino Acids	TRPV1: Y453, R534, K535, E536, I599, S629, Y631, F649, T650, A657, N652, D654, F655, K656, A657, V658, F659 DkTx: K1: W11, G12, K14, and F27 K2: W53, G54, K56 and F67
		Behavioral effects	Unknown
		Potency	EC50 = 0.23 µM
Chinese red-headed centipede Scolopendra subspinipes mutilans	RhTx [51]	Key Amino Acids	TRPV1: D602, Y632, T634, Possibly L461 RhTx: D20, K21, Q22, R15, E27
		Behavioral effects	Acute pain response when injected into mice
		Potency	EC50 = 521.5 ± 162.1 nM
Chinese Scorpion Mesobuthus martensii	BmP01 [59]	Key Amino Acids	TRPV1: E648, T651, E652
		Behavioral effects	Injection of 500 µM BmP01 evokes a pain response in wt mice but not in TRPV1 KO mice
		Potency	EC50(Ph=6.5) = 3.76 ± 0.4 µM EC50(Ph=7.5) = 169.5 ± 12.3 µM
Palestine saw-scaled viper Echis coloratus	F13 [69]	Key Amino Acids	Unknown
		Behavioral effects	Unknown
		Potency	Unknown
Sebae anemone Heteractis crispa	Heteractis crispa RG 21 (HCRG21) [34]	Key Amino Acids	HCRG21: E6, T14, P31 E38, R48, R51
		Behavioral effects	Unknown
		Potency	IC50 = 6.9 ± 0.4 µM
	Analgesic polypeptide Heteractis crispa (APHC1-3) [78]	Key Amino Acids	TRPV1: D648, E651, Y653, E636, Y627, D646 APHC: V31, R48, R51, R55
		Behavioral effects	▪dose-dependent inhibition of thermal nociception ▪APHC1 decreases both phases of the formalin test (acute and inflammatory pain). APHC3 attenuates only inflammatory phase ▪attenuates thermal hyperalgesia observed during CFA injection ▪Injection of APHC1 decreased body temperature by −0.8 °C within 30 min after administration. Injection of APHC3 decreases body temperature by 0.6 °C 60 min after administration.
		Potency	APHC1: IC50 = 6.9 ± 0.4 µM APHC3: IC50 = 18 nM