ART26-12- a novel fatty acid-binding protein 5 inhibitor- shows efficacy in multiple preclinical neuropathy models

Authors
W. G. Warren, M. Osborn, A. David-Pereira, C. Tsantoulas, Wenwen Xue, A. Yates, S. E. OSullivan


Lab

Journal
European Journal of Pain

Abstract
Our previous OIPN study showed that ART26.12 primarily exerted its analgesic effect via CB1, with involvement from CB2, TRPV1 and PPARα (Warren et al.,2024). While antagonist experiments and lipidomics were not conducted in the current study, it is likely that ART26.12 mediated its effects in these neuropathic pain models through similar mechanisms. Other cannabinoid agonists have produced CB1-dependent analgesia in platinum-based CIPN models (Bagher et al.,2023; Deng, Cornett, et al.,2015; Deng, Guindon, et al.,2015; Mulpuri et al.,2018; Pascual et al.,2005; Rahn et al.,2014; Sepulveda et al.,2022; Vera et al.,2013). Similarly, CB1- and CB2-dependent analgesia has been shown in diabetic neuropathy and cancer-induced bone pain, as well as PIPN (Deng et al.,2012; Gonçalves et al.,2022; Lin et al.,2022; Lozano-Ondoua et al.,2010,2013; Toniolo et al.,2022; Xu et al.,2014; Zeng et al.,2024; Zhang et al.,2018). TRPV1 and the wider eCB system are therapeutic targets in these pathologies (de Almeida et al.,2021; Liu et al.,2023; Rossato et al.,2018; Sun et al.,2019; Thompson et al.,2020; Xie et al.,2022; Zhang et al.,2019). Finally,N-arachidonoyl-glycine, a lipid previously shown to be elevated by ART26.12 (Warren et al.,2024), showed analgesic effects in a preclinical neuropathy model (Vuong et al.,2008). While these studies demonstrate a common mechanism of action across different neuropathies, activation of the eCB system also mediates analgesia in a wide variety of pain models. For example, FABP5 inhibition or knockdown produces CB1-dependent analgesia in inflammatory pain, osteoarthritis and chronic constriction injury (Berger et al.,2012; Bogdan et al.,2018,2022; Fauzan et al.,2022; Gordon et al.,2024; Kaczocha et al.,2014,2015; Peng et al.,2017; Yan et al.,2018; Zhu et al.,2023). Overall, this suggests that ART26.12 may also have therapeutic potential in chronic pain conditions with an inflammatory component.

Keywords/Topics
allodynia; neuropathy

BIOSEB Instruments Used:
Electronic Von Frey - Wireless (BIO-EVF-WRS),Electronic Von Frey 5 with embedded camera (BIO-EVF5)

Source :

https://onlinelibrary.wiley.com/doi/abs/10.1002/ejp.4718

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