Table 6.

Mollusk-derived toxins able to inhibit pain.

Toxin/ Molecule	Species	Production	Administration	Mechanism of Analgesia	Model	Ref.
Im10A (conotoxin)	Conus imperialis	Synthesized	Intramuscular injection (i.m.)	-	Rat PNL model	[131]
μ-Conotoxin TsIIIA	Conus tessulatus	Synthesized	Intrathecal (i.t.) injection	Inhibition of TTX (tetrodotoxin)-resistant sodium currents in DRG neurons	Hot-plate model	[132]
α-Conopeptide Eu1.6	Conus eburneus	Synthesized	Intramuscular injection (i.m.) and intravenous (i.v.) injection	Inhibition of high voltage-activated N-type calcium channel currents (Cav2.2) in isolated mouse dorsal root ganglia (DRG) neurons	Rat partial sciatic nerve injury (PNL model) and chronic constriction injury pain (CCI model) models	[102]
ω-Conotoxins: MoVIA and MoVIB	Conus Moncuri	Purified from venom and synthesized	Intrathecal (i.t.) injection	Inhibition of rat Cav2.2 channels	PNL-induced neuropathic pain	[134]
α-Conotoxin Vc1.1 Variants	-	Synthesized	Intramuscular (im.i), injection	Inhibition of G protein-coupled γ-aminobutyric acid type B receptors (GABABR) coupled Cav2.2 channels in rat DRG neurons	PNL and CCI models	[135]
cVc1.1 and cVc1.1 analogues: [C2H, C8F]cVc1.1 and [N9W]cVc1.1	-	Synthesized	Intra-colonic administration	Reduction in the excitability of DRG neurons	Chronic visceral hypersensitivity (CVH model)	[142]
ω -Conotoxin MVIIA modified	-	Synthesized	Intravenously (i.v.) injection and intranasally injection	-	Hot-Plate model	[144]
αO-Conotoxin GeXIVA	Conus generalis	Synthesized	Intramuscular (im.i), injection	-	Oxaliplatin-induced neuropathic pain, cold and mechanical allodynia	[137]
Partially purified conotoxins (C1-C7) of C. coronatus and C. frigidus (F1-F6).	Conus coronatus and Conus frigidus	Purified from Venom	Intraperitoneal (i.p.) injection	Only C2 had analgesic effects in both tested models; mechanism of analgesia: not studied	Hot-plate model and formalin-induced pain	[145]
BuIA conotoxin analogues	Conus bullatus	Synthesized	Intraperitoneal (i.p.) injection	All the analogs showed the same analgesic activity of BuIA Mechanism of analgesia: not studied	Hot-plate model and paclitaxel-induced neuropathic pain	[138]
ω-conotoxin Bu8	Conus bullatus	Synthesized	Intraperitoneal (i.p.) injection	Inhibition of Cav2.2	Hot-plate model and analgesic activity to acute pain and inflammatory pain	[146]
Conotoxin-Ac1// Conotoxin-Ac1-O6P (variant)	Conus achatinus	Synthesized	Intrathecal (i.t.) injection	Inhibition of NR2B ion channels	Hot-plate and tail-flick models	[141]
α-Conotoxin Vc1.1 modified	Conus victoriae	Purified from venom and modified	Intramuscular (im.i), injection	Activation of GABABRs expressed in DRG	Spinal nerve ligation-induced neuropathic pain (SNL model), mechanical allodynia	[136]
α4/7-Conotoxin (Lv1d)	Conus lividus	Synthesized	Intrathecal (i.t.) injection (mouse hot plate model) Intramedullary injection (formalin-induced pain model)	-	Mouse hot-plate and formalin-induced pain models	[147]
µ-Conotoxin S24a	Conus striatus	Synthesized	Intrathecal (i.t.) injection	-	Mouse hot-plate and formalin-induced pain models	[148]
ω-Conotoxin	Conus virgo	Purified from venom and modified	Intraperitoneal (i.p.) injection	-	Central analgesic assay (tail immersion test) and Peripheral analgesic assay (acetic acid-induced writhing test)	[149]
α-CTx RgIA analogues (RgIA-5524)	-	Synthesized	Subcutaneous (i.s.) injection	Inhibition of α9-containing nicotinic acetylcholine receptors (nAChRs)	Oxaliplatin-induced neuropathic pain	[143]
α-Conotoxin RgIA analogues (RgIA-5474)	-	Synthesized	Subcutaneous (i.s.) injection	-	Oxaliplatin-induced neuropathic pain, cold allodynia	[139]
ω–Conotoxins: MVIIA, GVIA and CVIF	-	Obtained from Alomone Labs (Jerusalem, Israel).	Intraplantar (i.pl.). injection	-	Post-surgical pain (PSP model) and cisplatin-induced pain neuropathy and oxaliplatin-induced neuropathic pain	[140]