PhD Scientific Days 2025

Poster Session I. - Q: Neurosciences

Simultaneous Administration of Phenylephrine with Pregabalin in Neuropathic Rats Produces an Acute Antiallodynic Effect

Name of the presenter

Abbood Sarah

Institute/workplace of the presenter

Semmelweis university

Authors

Sarah Abbood^1,2, Nariman Essmat^1,2, Imre Boldizsár^1,2, Ildikó Miklya^1,2, Kornél Király^1,2, Laszlo G Harsing Jr^1,2, Zoltan Giricz^1,2, Csenger Kovácsházi^1,2, Mahmoud Al-Khrasani^1,2

1: Department of Pharmacology and Pharmacotherapy, Semmelweis University
2: Center for Pharmacology and Drug Research & Development, Semmelweis University, Budapest, Hungary

Text of the abstract

Introduction: Neuropathic pain (NP) treatment remains unresolved thus far. The spinal cord is a crucial relay point in pain transmission and modulation. The adrenergic system modulates spinal pain perception, positioning it as a potential target for drug development. Phenylephrine (PE) is regarded as a selective α1-adrenoreceptor (AR) agonist, but previous studies, including ours, suggest it induces an indirect, non-calcium-dependent release of cytosolic norepinephrine (NE), similar to tricyclic antidepressants that enhance NE in the descending pain pathway, leading us to hypothesize that PE may have an antiallodynic effect.
Aims: Investigation of the effects of PE on mononeuropathic pain induced by partial sciatic nerve ligation (pSNL) in rats following per se intrathecal (it.) or oral administration, as well as in combination with pregabalin (PGB) after acute and chronic administrations. Elucidate the mechanisms of action and assess side effects related to motor function and blood pressure (BP).
Methods: Male Wistar rats underwent pSNL to induce tactile allodynia, the hallmark of NP. Allodynia was characterized by a decrease in the paw withdrawal threshold, measured by a Dynamic Plantar Aesthesiometer 2 weeks post-surgery. It. administration was achieved through direct injection, and oral administration was conducted by gavage. Prazosin and idazoxan are selective antagonists for α1 and α2 ARs, respectively, and were used to elucidate the mechanism of action of PE. The rotarod test was used to assess motor function. BP and heart rate were also assessed.
Results: After it, PE at 30 nmol /rat produced prazosin and idazoxan-sensitive antiallodynic effect in the operated paws. On the other hand, oral PE/PGB (5/25mg/kg) combination resulted in a significant antiallodynic effect following both acute and chronic treatment. This combination was devoid of side effects related to motor function or cardiovascular effects.
Conclusions: PE is a promising candidate for treating mononeuropathic pain when administered alone or in combination with PGB. This effect is mediated by α1 and α2 ARs; however, future studies are required to elucidate this issue. This work provides evidence of cooperation between ARs and voltage-gated calcium channels hosting α2δ subunits in the context of antiallodynia.
Funding: TKP 2021 EGA-25, SE 250+ Excellence PhD Scholarship, EKÖP 2024.