Lack of efficacy of a partial adenosine A1 receptor agonist in neuropathic pain models in mice

  • Previous studies suggest that adenosine A1 receptors (A1R) modulate the processing of pain. The aim of this study was to characterize the distribution of A1R in nociceptive tissues and to evaluate whether targeting A1R with the partial agonist capadenoson may reduce neuropathic pain in mice. The cellular distribution of A1R in dorsal root ganglia (DRG) and the spinal cord was analyzed using fluorescent in situ hybridization. In behavioral experiments, neuropathic pain was induced by spared nerve injury or intraperitoneal injection of paclitaxel, and tactile hypersensitivities were determined using a dynamic plantar aesthesiometer. Whole-cell patch-clamp recordings were performed to assess electrophysiological properties of dissociated DRG neurons. We found A1R to be expressed in populations of DRG neurons and dorsal horn neurons involved in the processing of pain. However, administration of capadenoson at established in vivo doses (0.03–1.0 mg/kg) did not alter mechanical hypersensitivity in the spared nerve injury and paclitaxel models of neuropathic pain, whereas the standard analgesic pregabalin significantly inhibited the pain behavior. Moreover, capadenoson failed to affect potassium currents in DRG neurons, in contrast to a full A1R agonist. Despite expression of A1R in nociceptive neurons, our data do not support the hypothesis that pharmacological intervention with partial A1R agonists might be a valuable approach for the treatment of neuropathic pain.
Author:Katharina Metzner, Tilman GroßGND, Annika Balzulat, Gesine Wack, Ruirui LuGND, Achim SchmidtkoORCiDGND
Parent Title (English):Purinergic signalling
Publisher:Springer Science + Business Media B.V.
Place of publication:Dordrecht
Document Type:Article
Date of Publication (online):2021/07/27
Date of first Publication:2021/07/27
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2022/03/16
Tag:Adenosine A1 receptor; In situ hybridization; Neuropathic pain; Pain behavior; Partial agonist; Patch-clamp
Page Number:12
First Page:503
Last Page:514
Open Access funding enabled and organized by Projekt DEAL. This study was supported by the Grants4Indications™ initiative of Bayer AG, Leverkusen, Germany, and by European Regional Development Fund/LeitmarktAgentur.NRW (EFRE-0800971/LS-1–2-023d).
Institutes:Biochemie, Chemie und Pharmazie
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0