IGF-1 and Migraine
IGF-1 significantly reduces susceptibility to cortical spreading depression, the cause of migraine aura and likely related migraine pain. A burst of aberrantly increased brain excitability initiates cortical spreading depression. IGF-1 effectively inhibits this initiating hyperexcitability by reducing inflammation and associated production of free radicals. This protective effect was initially demonstrated in cultured rodent brain slices, and later studies show that nasal delivery of IGF-1 is similarly protective against cortical spreading depression in rodents. This effect occurs within an hour after administration of a single dose, lasts for at least a week, and can be enhanced by repeated dosing.
Nasal delivery of IGF-1 also significantly inhibits head pain-related trigeminal system activation from cortical spreading depression, a well-recognized preclinical model of migraine. This effect involves significant reductions in trigeminal ganglion oxidative stress as well as calcitonin gene-related peptide (CGRP), documented migraine pain mediators. In fact, nasal delivery of IGF-1 significantly reduces trigeminal ganglion CGRP before headache onset when it otherwise could be released and contribute to headache pain.
The ability of nasal IGF-1 to protect against trigeminal system pain-related activation is also evident after nitroglycerin treatment. Nitroglycerin triggers migraine in patients and is a second, well-accepted preclinical model of migraine. Pretreatment of rodents with nasal IGF-1 significantly reduces trigeminal pain system activation and related elevation in trigeminal ganglion oxidative stress and CGRP.
Taken together, these dual studies show that nasal delivery of IGF-1 may be a novel, naturally occurring means to mitigate brain initiation of migraine and the downstream sensory system head pain.