BotAF, a new Buthus occitanus tunetanus scorpion toxin, produces potent analgesia in rodents

Riadh Maatoug (1) , Jed Jebali (1) , Régis Guieu (2) , Michel de Waard (3, 4) , Riad Kharrat (1)

1 LR11IPT08 - Laboratoire des Venins et Biomolécules Thérapeutiques - Laboratory of Venoms and Therapeutic Biomolecules
2 TIMONE - Hôpital de la Timone [CHU - APHM]
3 ITX - ITX - unité de recherche de l'institut du thorax
4 Bâtiment Biopolis - Smartox Biotechnology [Saint Martin d'Hères]

This work reports the purification of new potent scorpion neuropeptide, named BotAF, by an activity-guided screening approach. BotAF is a 64-residue long-chain peptide that shares very high similarity with the original β-like scorpion toxin group, in which several peptides have been characterized to be anti-nociceptive in rodents. BotAF administration to rodents does not produce any toxicity or motor impairment, including at high doses. In all models investigated, BotAF turned out to be an efficient peptide in abolishing acute and inflammatory (both somatic and visceral) pain in rodents. It performs with high potency compared to standard analgesics tested in the same conditions. The anti-nociceptive activity of BotAF depends on the route of injection: it is inactive when tested by i.c.v. or i.v. routes but gains in potency when pre-injected locally (in the same compartment than the irritant itself) or by i.t. root 40 to 60 min before pain induction, respectively. BotAF is not an AINS-like compound as it fails to reduce inflammatory edema. Also, it does not activate the opioidergic system as its activity is not affected by naloxone. BotAF does also not bind onto RyR and has low activity towards DRG ion channels (particularly TTX sensitive Na+ channels) and does not bind onto rat brain synaptosome receptors. In somatic and visceral pain models, BotAF dose-dependently inhibited lumbar spinal cord c-fos/c-jun mRNA up regulation. Altogether, our

Mots clés: Analgesia; Long chain scorpion toxins; Venom; Buthus occitanus tunetanus; Bio-guided screening; Antinociception

Domaines: Sciences du Vivant [q-bio]

Riadh Maatoug, Jed Jebali, Régis Guieu, Michel de Waard, Riad Kharrat. BotAF, a new Buthus occitanus tunetanus scorpion toxin, produces potent analgesia in rodents. Toxicon, 2018, ⟨10.1016/j.toxicon.2018.01.003⟩. ⟨hal-01760796⟩