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Papers of the Week

Papers: 24 Jul 2021 - 30 Jul 2021

Animal Studies, Pharmacology/Drug Development

2021 Jul 27

Purinergic Signal

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


Metzner K, Gross T, Balzulat A, Wack G, Lu R, Schmidtko A
Purinergic Signal. 2021 Jul 27.
PMID: 34313915.


Previous studies suggest that adenosine A receptors (AR) modulate the processing of pain. The aim of this study was to characterize the distribution of AR in nociceptive tissues and to evaluate whether targeting AR with the partial agonist capadenoson may reduce neuropathic pain in mice. The cellular distribution of AR 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 AR 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 AR agonist. Despite expression of AR in nociceptive neurons, our data do not support the hypothesis that pharmacological intervention with partial AR agonists might be a valuable approach for the treatment of neuropathic pain.