This technology includes a class of A3AR-selective agonists to be used therapeutically to treat a variety of conditions, including chronic pain, cancer, and inflammatory diseases. This class of compounds produced full agonists of the human A3AR of nanomolar affinity that were consistently highly selective (>1000-fold vs. A1AR and A2AAR). The selectivity at mouse A3 receptors is smaller, but the compounds are still effective in vivo in reducing or preventing development of neuropathic pain. The advantages over previous, structurally similar compounds are a smaller molecular weight, and therefore greater oral bioavailability. We have carried out phenotypic screening – thus we have identified unexpected in vivo activity of specific C2 substituents in a chronic neuropathic pain model.