Antinociceptive and neuromodulatory effects of the scorpion venom tetrapeptide tetrascorpin-1 in a long-lasting pain hypersensitivity model in mice

Posted by

 


Antinociceptive and neuromodulatory effects of the scorpion venom tetrapeptide tetrascorpin-1 in a long-lasting pain hypersensitivity model in mice

Abstract

We evaluated the effects of Tetrascorpin-1 from Androctonus australis (AaTs-1), a tetrapeptide obtained from scorpion venom, previously hypothesized to bind the formyl peptide receptor like-1 (FPRL-1) known as formyl peptide receptor-2 (FPR-2) in vitro, on pain responses and cytokines, neuronal and glial morpho-functional alterations in the spinal cord of mice with formalin-induced long-lasting pain hypersensitivity. Due to the peptide chemical nature and for favoring its penetration into the central nervous system, AaTs-1 was daily administered intranasally for 10 days. In formalin-injected mice the AaTs-1 treatment abolished mechanical allodynia, thermal hyperalgesia, hyperactivation of spinal nociceptive-specific (NS) neurons, and partially restored spinal anti-inflammatory/pro-inflammatory cytokine levels and microglia/astrocyte phenotype alterations. Additionally, in contrast to what occurred in formalin-injected mice, AaTs-1 treatment facilitated the firing activity of NS neurons and consistently altered the levels of some spinal cytokines under investigation in healthy mice. Based on the opposing effects of AaTs-1 under physiological and pathological conditions, we suspect that it acts as a partial agonist in vivo rather than as an antagonist of FPR-2, as other in vitro data would suggest.
Pagano, S., Limongelli, R., Moslah, W., Saada, M., Manzo, I., Bonsale, R., Teweldemedhin, M. M., Fusco, A., Guida, F., Belardo, C., Morace, A. M., Perrone, M., Ricciardi, F., Pierretti, G., Vastarella, M. G., Infantino, R., Srairi-Abid, N., Maione, S., Palazzo, E., . . . Luongo, L. (2025). Antinociceptive and neuromodulatory effects of the scorpion venom tetrapeptide tetrascorpin-1 in a long-lasting pain hypersensitivity model in mice. Toxicon, 108611. https://doi.org/10.1016/j.toxicon.2025.108611