Cellular and Molecular Neurobiology
Author: Emanuel David Peralta | Email: peralta.emanuel@hotmail.com
Emanuel David Peralta1°2°, Cristian Gabriel Acosta1°2°
1° Instituto dInstituto de Histología y Embriología de Mendoza (IHEM)e
2° CONICET
Chronic pain affects approximately 3% to 17% of the general population, yet current therapeutic approaches remain largely ineffective. The Renin-Angiotensin-Aldosterone System (RAAS) emerges as a promising target for novel treatments. RAAS components are present in Dorsal Root Ganglion (DRG) neurons, and their modulation has shown neuroprotective effects in neuropathic pain conditions. On the other hand, K2P channels determine the resting membrane potential, affecting neuronal excitability and facilitating the firing of action potentials. This study investigates the modulatory effects of Angiotensin-II type 1 and 2 receptors (AT1R and AT2R) on TWIK1, an important K2P potassium channel in DRG neurons, and their analgesic effects in a Wistar rat model of neuropathic pain. We employed immunohistochemistry, qPCR, and in vivo pharmacology, antagonizing AT1R and AT2R with Telmisartan and PD123319, respectively. We assessed their impact on nociceptive responses to mechanical and cold stimuli. Our findings indicate a attenuation of pain with PD123319 administration. Immunohistochemical analysis revealed significant co-expression of TWIK1 with AT1-AT2 in DRG neurons, as well as an increase in TWIK1 expression in neuropathic rats treated with Telmisartan and Telmisartan+PD123319. This was confirmed by qPCR in DRG tissue subjected to the same treatments. Our results suggest that the observed analgesic effect may reflect modulation by the RAAS of K2P channels in nociceptive neurons.