Table 3.

Spider-derived toxins able to inhibit pain.

Toxin/ Molecule	Species	Production	Administration	Mechanism of Analgesia	Model	Ref.
PhTx3-4	Phoneutria nigriventer	Purified from venom	Intrathecal (i.t.) injection	Reduction in glutamate levels in the cerebrospinal fluid	Persistent inflammatory pain and post-operative (plantar incision) nociception in mice	[92]
PnPP-19	Phoneutria nigriventer	Synthesized	Subcutaneous (s.c.) injection	Both opioid and cannabinoid peripherical systems	Hyperalgesia induced by the administration of PGE2	[94]
Tx3-5	Phoneutria nigriventer	Purified from venom	Intrathecal (i.t.) injection	-	Postoperative (plantar incision), neuropathic (partial sciatic nerve ligation), and cancer-related pain (inoculation with melanoma cells) in animals	[105]
δ-CNTX-Pn1a	Phoneutria nigriventer	Purified from venom	Intrathecal (i.t.) injection	Opioid and cannabinoid systems	Hyperalgesia induced by the CCI model and hyperalgesia induced by the administration of PGE2	[93]
PnPP-19	Phoneutria nigriventer	Synthesized	Subcutaneous (s.c.) injection	Activation of NO-cGMP-KATP pathway	Hyperalgesia induced by the administration of PGE2	[95]
PhKv	Phoneutria nigriventer	Purified from a PhTx3 fraction	Intrathecal (i.t.) injection	Inhibition of spinal AChE resulting in the activation of the muscarinic and nicotinic receptors	Chronic constriction injury model and after intraplantar injection of capsaicin	[97]
Phα1β	Phoneutria nigriventer	Purified from venom	Intrathecal (i.t.) or intraplantarly (i.pl.) injections	Selective antagonist of TRPA1 channels	Nocifensive responses evoked by reactive TRPA1 channel agonist, mechanical and cold hyperalgesia, neuropathic pain induced by the chemotherapeutic agent bortezomib	[106]
Pha1β	Phoneutria nigriventer	Purified from venom	Intrathecal (i.t.) injection	Reversibly inhibits the voltage-gated calcium channels (VGCC)	Nociception that was triggered by capsaicin, CCI model, and hyperalgesia was induced in the melanoma cancer pain model	[97]
Pha1β	Phoneutria nigriventer	Recombinant	Intrathecal (i.t.) injection	Reversibly inhibits the voltage-gated calcium channels (VGCC)	Nociception that was triggered by capsaicin, CCI model, and hyperalgesia was induced in the melanoma cancer pain model	[97]
PnTx4(5-5)	Phoneutria nigriventer	Purified from venom	Intraplantarly (i.pl.) and subcutaneous (s.c.) injection	The antinociceptive effect of PnTx4(5-5) can also be related to the glutamatergic system	Hyperalgesia induced by PGE2, carrageenan, and L-glutamate (L-Glu)	[107]
Phα1β	Phoneutria nigriventer	Recombinant	Intravenous (i.v.) injection	-	Pain was induced by the CCI model and paclitaxel-induced acute and chronic pain	[108]
CTK 01512-2	Phoneutria nigriventer	Recombinant	Intrathecal (i.t.) injection	Reversibly, and not specifically a block of Cav 2.2 that affects the intracellular Ca2+ influx and the glutamate release	Mechanical and thermal hyperalgesia and cold allodynia	[109]
Phα1β	Phoneutria nigriventer	Purified from venom	Intrathecal (i.t.) injection	Blocker voltage-dependent calcium channels and the antagonism with the receptor CXCR4	Diabetic neuropathic pain	[98]
PnAn13	Phoneutria nigriventer	Synthetic peptide	Intrathecal (i.t.) injection	Opioid and cannabinoid systems	Hyperalgesia induced by PGE2	[110]
Phα1β	Phoneutria nigriventer	-	Intrathecal (i.t.) injection	Blocker TRPA1 and Cav2.2 receptors	Postoperative (plantar incision)	[111]
Phα1β	Phoneutria nigriventer	Recombinant	Intravenous (i.v.) injection	High-voltage calcium channel inhibitors (HVCCs) and cationic channel antagonists of the potential transient receptor (TRPA1)	Hyperalgesia and mechanical allodynia induced by reserpine (fibromyalgia)	[112]
Cd1a	Ceratogyrus darlingi	Chemical synthesis	Intraplantar (i.pl.) injection	Nav/Cav channel inhibitor	Peripheral pain by NaV channels induced with α-scorpion toxin OD1	[87]
JZTX-X	Chilobrachys jingzhao	Chemical synthesis	Intraplantar (i.pl.) injection	Kv4 channel inhibitor	Mechanical hypersensitivity	[100]
μ-TRTX-Ca2a	Cyriopagopus albostriatus	Purified from venom	Intrathecal (i.t.) and intraplantar (i.pl.) injection	Na v 1.7 channel inhibitor	Acute inflammation models induced by formalin and acetic acid and acute thermal pain models induced by hot plate	[101]
µ-TRTX-Ca1a	Cyriopagopus albostriatus	Purified from venom	Intraperitoneal (i.p.) injection	hNa v 1.7 channel inhibitor	Pain formalin-induced paw licking, hot plate test, and acetic acid-induced writhing	[102]
CyrTx-1a	Cyriopagopus schioedtei	Purified from venom	Intraperitoneal (i.p.) injection	hNa V 1.7 channel inhibitor	Thermal hyperalgesia	[103]
Df1a-NH2	Davus fasciatus	Chemical synthesis	Intraplantar (i.pl.) injection	NaV and CaV3 channel inhibitor	Peripheral pain by NaV channels induced with α-scorpion toxin OD1	[88]
Df1a-OH	Davus fasciatus	Chemical synthesis	Intraplantar (i.pl.) injection	NaV and CaV3 channel inhibitor	Peripheral pain by NaV channels induced with α-scorpion toxin OD1	[88]
GpTx-1 and GpTx-1-71	Grammostola porteni	Chemical synthesis	Intrathecal (i.t.) and Intracerebroventricular (i.c.v.) injection	Nav channel inhibitor	Tail-flick test, carrageenan- or complete Freund’s adjuvant (CFA)-induced inflammatory pain model, neuropathic pain model, mechanical allodynia, thermal hyperalgesia, writhing test, formalin test, tolerance evaluation, rotarod test, open field test, gastrointestinal transit test	[104]
HpTx3	Heteropoda venatoria	Purified from venom	Intramuscular (im.i) and intraperitoneal (i.p.) injections	Nav1.7 channel inhibitor	Acute inflammation models induced by formalin and acetic acid, chronic inflammation pain models induced by complete Freund’s adjuvant, acute thermal pain models induced by hot plate, and chronic neuropathic pain models induced by spared nerve injury	[90]
μ-theraphotoxin-Pn3a	Pamphobeteus nigricolor	Purified from venom	Intraperitoneal (i.p.) injection	Nav1.7 channel inhibitor and synergy with opioids	Peripheral pain by NaV channels induced with α-scorpion toxin OD1	[99]
ProTx-III	Thrixopelma pruriens	Recombinant	Intraplantar (i.pl.) injection	Nav1.7 channel inhibitor	Peripheral pain by NaV channels induced with α-scorpion toxin OD1	[91]
ProTx-II (β/ω-terafotoxina-Tp2a)	Thrixopelma pruriens	-	Intracerebroventricular (i.cv) injection	Nav1.7 channel inhibitor	Acute thermal pain model induced by hot plate and mechanical allodynia	[96]