Table 4.

Current toxins in in vivo preclinical and human clinical trials showing promising therapeutic efficacy for treating chronic pain

Toxin	Organism Species	NaV subtypes targeted	Preclinical/clinical studies showing therapeutic efficacy	Reference
TTX	Puffer fish Family Tetraodontidae	NaV1.1–NaV1.4, NaV1.6 and NaV1.7	Inflammatory and neuropathic muscle mechanical hyperalgesia	Alvarez and Levine (2015)
			Inflammatory thermal and mechanical pain	Beloeil et al. (2006)
			Inflammatory, visceral and neuropathic pain	Marcil et al. (2006)
			Burn‐associated neuropathic pain	Salas et al. (2015)
			Chemotherapy‐induced neuropathic pain (clinical trials)	Wex Pharmaceutical Inc.
Neosaxitoxin	Dinoflagellates	NaVs	Bladder pain syndrome (clinical trials)	Manriquez et al. (2015)
Gonyautoxin	Dinoflagellates	NaVs	Chronic tension‐type headache (clinical trials)	Lattes et al. (2009)
ProTx‐II	Spider T. pruriens	NaV1.7	Painful diabetic neuropathy	Tanaka et al. (2015)
			Inflammatory pain	Flinspach et al. (2017), Patent US20150099705 A1
HnTX‐IV	Spider H. haianum	NaV1.2, NaV1.3 and NaV1.7	SNI‐induced neuropathic pain and formalin‐induced inflammatory pain	Liu et al. (2014a)
μ‐TRTX‐Hl1a	Spider H. lividium	NaV1.8	Inflammatory and neuropathic pain	Meng et al. (2016)
HwTx‐IV	Spider O. huwena	NaV1.7	Inflammatory pain and SNI‐induced neuropathic pain	Liu et al. (2014b)
μ‐TRTX‐Pn3a	Spider P. nigricolor	NaV1.7	Inflammatory pain, co‐administrated with opioid	Deuis et al. (2017)
μO‐MrVIB	Cone snail C. marmoreus	NaV1.8	Allodynia and hyperalgesia associate to neuropathic and chronic inflammatory pain	Ekberg et al. (2006)
			Post‐incision allodynia	Bulaj et al. (2006)
μO‐MfVIA	Cone snail C. magnificus	NaV1.4 and NaV1.8	Inflammatory pain (analogue E5K and E8K MfVIA)	Deuis et al. (2016a)
μ‐KIIIA	Cone snail C. kinoshitai	NaV1.2, NaV1.4, NaV1.6 and NaV1.7	Inflammatory pain	Zhang et al. (2007) and Han et al. (2009)
μ‐SIIIA	Cone snail C. striatus	NaV1.2, NaV1.4 and NaV1.6	Inflammatory pain	Green et al. (2007)