TY  - JOUR
A1  - Metzner, Katharina
A1  - Groß, Tilman
A1  - Balzulat, Annika
A1  - Wack, Gesine
A1  - Lu, Ruirui
A1  - Schmidtko, Achim
T1  - Lack of efficacy of a partial adenosine A1 receptor agonist in neuropathic pain models in mice
T2  - Purinergic signalling
N2  - 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.
KW  - Neuropathic pain
KW  - Adenosine A1 receptor
KW  - Partial agonist
KW  - Pain behavior
KW  - In situ hybridization
KW  - Patch-clamp
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/63572
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-635729
SN  - 1573-9546
N1  - 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).
VL  - 17
IS  - 3
SP  - 503
EP  - 514
PB  - Springer Science + Business Media B.V.
CY  - Dordrecht
ER  -