Abstract
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.
Highlights
Traumatic injuries, surgical insults and damages of peripheral nerves often lead to neuropathic pain, a chronic debilitating disease that affects 7–10% of the general population and is associated with great impairment of quality of life [1]
To analyze the localization of A 1R in dorsal root ganglia (DRG) neuron subpopulations we combined in situ hybridization of A1R mRNA with immunostaining for established markers (Fig. 1c-f)
We investigated whether the partial A1R agonist capadenoson might be sufficient for treatment of neuropathic pain
Summary
Surgical insults and damages of peripheral nerves often lead to neuropathic pain, a chronic debilitating disease that affects 7–10% of the general population and is associated with great impairment of quality of life [1]. More than half of neuropathic pain patients report inadequate pain relief with currently available medications, and these are often associated with severe dose-limiting side effects. There is a large unmet therapeutic need for effective and safe treatment of neuropathic pain [2,3,4]. Neuropathic pain is associated with multiple alterations in the peripheral and central nervous system [5, 6]. Accumulating evidence indicates that the nucleoside adenosine contributes to the processing of neuropathic pain [7, 8].
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