Regulation by cAMP of native HCN channels plays crucial physiological roles: in the sinoatrial node, it underlies the autonomic regulation of the heartbeat (DiFrancesco and Tortora, 1991); in pathophysiological conditions, such as in peripheral neuropathic pain, cAMP modulation of HCN channels leads to neuronal hyperexcitability enhancing pain transmission (Emery et al., 2011). This evidence concerns the gene MALAT1 and Pain.