P3.51. IN VIVO INVESTIGATION OF THE SEX-DEPENDENT ANALGESIC EFFECTS OF HISTAMINE H4 RECEPTOR ANTAGONIST IN A MURINE MODEL OF NEUROPATHIC PAIN
Maciej Degutis1, Magdalena Białoń1, Magdalena Maciuszek1, Małgorzata Więcek2, Tadeusz Karcz2, Katarzyna Szczepańska3, Aleksandra Pędracka1, Katarzyna Kieć-Kononowicz2, Katarzyna Starowicz1, Katarzyna Popiołek-Barczyk1
1 Maj Institute of Pharmacology, Polish Academy of Sciences, Department of Neurochemistry, Krakow, 31-343, Poland
2 Jagiellonian University Medical College, Department of Technology and Biotechnology of Drugs, Krakow, 30-688, Poland
3 Maj Institute of Pharmacology, Polish Academy of Sciences, Department of Medicinal Chemistry, Krakow, 31-343, Poland
INTRODUCTION: Neuropathic pain is a complex condition significantly modulated by neuroimmune interactions. The histamine H4 receptor (H4R) has emerged as a promising target for pharmacological intervention, with its expression strongly associated with immune responses.
AIM(S): This study aimed to investigate the mechanism of action of a novel H4R antagonist (JSJ; 5-chloro-1H-indol-2-yl)(4-methylpiperazin-1-yl)methanethione hydrochloride) in neuropathic male and female mice, and its influence on spinal astrocyte activation.
METHOD(S): We assessed the effects of JSJ on mechanical (von Frey) and thermal (cold plate, tail flick) stimuli in a chronic constriction injury (CCI) model in both sexes. Single (1, 10, 20 mg/kg, i.p.) and repeated (20 mg/kg, i.p., twice daily for 7 days) JSJ administrations were evaluated. H4R expression and JSJ’s impact on astrocyte activation (GFAP level) were examined using immunohistochemistry and Western blotting, respectively.
RESULTS: A single JSJ injection attenuated thermal hyperalgesia in neuropathic females. In contrast, repeated administration significantly reduced mechanical allodynia in CCI-exposed males. Biochemical analyses revealed nerve injury-induced upregulation of GFAP in males, but not in females. JSJ treatment did not significantly affect GFAP levels. H4R expression was confirmed in spinal astrocytes in both sexes.
CONCLUSIONS: These findings underscore sex-dependent differences in the analgesic effects of H4R antagonism, potentially mediated by divergent astrocytic activation profiles.
FINANCIAL SUPPORT: This work was financed by a grant from the National Science Centre, Poland, SONATA 2019/35/D/NZ7/01042.