Efficacy of monoclonal antibodies against CGRP or its receptor (calcitonin receptor-like receptor/receptor activity modifying protein-1, CLR/RAMP1) implicates peripherally released CGRP in migraine pain. CLR/RAMP1 activation in human and mouse Schwann cells generates long-lasting signals from endosomes that evoke cAMP-dependent formation of NO. The gene discussed is RAMP1; the disease is migraine disorder.