Targeting the central projection of the dural trigeminovascular system for migraine prophylaxis

Migraine abortives likely target both peripheral-dural and central trigeminovascular mechanisms in mediating their therapeutic effects. However, in preclinical assays, many migraine preventives have little success at inhibiting similar trigeminovascular-mediated peripheral changes within the dural microenvironment. In addition, their effects on central trigeminovascular neuronal responses are largely unknown. Using a validated preclinical model of acute dural-intracranial (migraine-like) head pain, using Sprague Dawley rats, we tested whether migraine preventives suppress ongoing firing of central trigeminocervical neurons, and evoked responses to cranial neurovascular activation. Flunarizine, sodium valproate, propranolol, and amitriptyline, all dose-dependently inhibited ongoing spontaneous firing of dural trigeminovascular neurons, and differentially affected neuronal responses to intracranial-dural and extracranial-cutaneous somatosensory stimulation. Lamotrigine, only effective in the treatment of mi...