This technology includes (N)-methanocarba derivatives that are selective agonists of the A3 receptor to be used for the treatment of chronic neuropathic pain. 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. We have carried out phenotypic screening – thus we have identified unexpected in vivo activity of specific C2 substituents in a chronic neuropathic pain model.