Functional modulation of primary afferent neurons and post-ganglionic sympathetic neurons by statins
Registration code: PN-IV-P1-PCE-2023-0315
Project code: 80PCE/2025
Contract start date: 01.07.2025
Contract end date: 30.06.2028
Project duration: 36 months
Allocated amount: 1.147.368,00 lei
Acronym: STATPAIN
Project director: Prof. Alexandru Babeş, PhD; e-mail: alexandru.babes@bio.unibuc.ro
Project team: Assoc. Prof. Tudor Selescu; Dan Domocos, PhD; Assist. Prof. George Opriţă, PhD student; Adelina Păduraru, PhD student
Abstract
Statins are frequently used for the treatment of atherosclerotic disease. Besides inhibiting cholesterol biosynthesis, a number of so-called pleiotropic effects of these drugs have been documented, which are independent on their cholesterol-lowering action. While the mechanisms involved in their anti-inflammatory and anti-oxidant effects are relatively well understood, this is not the case as far as the anti-nociceptive and sympatholytic effects of statins are concerned. It has been shown that statins inhibit the generation of certain isoprenoid intermediates in the mevalonate pathway, leading to reduced isoprenylation of the Ras superfamily of small GTPases, which triggers the anti-inflammatory and anti-oxidant effects of statins. Using a combination of molecular, cellular and functional (optical and electrophysiological) methods, this project aims to explore the mechanisms involved in the statin-induced modulation of the excitability and chemosensitivity of sensory and sympathetic neurons in the peripheral nervous system, as a putative basis for their anti-nociceptive and sympatholytic effects. Among the molecular targets to be investigated are certain Transient Receptor Potential channels and voltage-sensitive sodium channels, key molecules involved in pain signalling and control of post-ganglionic sympathetic neurons. The intracellular signalling pathways involved will also be identified.
Publications resulting from the project: Oprita, G., Domocos, D., Selescu, T., Paduraru, A., Tunaru, S., Leffler, A., Babes, A., Babes, R.M. (2025), “Statins activate temperature-gated transient receptor potential ion channels”, European Journal of Pharmacology, 1006:178206. IF = 4.7
The scientific report of the project “Modulation of primary afferent neurons and postganglionic sympathetic neurons by statins” – December 2025 can be accessed HERE.
