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Neurostimulation for Primary Headache Disorders: Part 2, Review of Central Neurostimulators for Primary Headache, Overall Therapeutic Efficacy, Safety, Cost, Patient Selection, and Future Research in Headache Neuromodulation


  • Conflict of Interest: Dr. Jenkins has no disclosures. Dr. Tepper receives research grants to the Cleveland Clinic from Autonomic Technologies, Inc, Boston Scientific, GSK, MAP, Merck, NuPathe, and Zogenix. He served as a consultant for GSK, MAP, Merck, Nupathe, and Zogenix. He served on the Speakers Bureau for GSK, Nautilus, Merck, and Zogenix. He served on an Advisory Board for Helsinn, Merck, MAP, Nautilus, Nupathe, and Zogenix.

S.J. Tepper, Cleveland Clinic, Headache Center, T33, 9500 Euclid Avenue, Cleveland, OH 44195, USA, email:


This article is the second of 2 articles reviewing neurostimulation for primary headaches. In Part 1, we described methods, pathophysiology and anatomy, and history of neuromodulation in the treatment of headache, as well as reviewing the literature on peripheral neuromodulation for primary headaches. Peripheral targets for stimulation include percutaneous nerves, transcranial holocephalic, occipital nerves, auriculotemporal nerves, supraorbital nerves, cervical epidural, and sphenopalatine ganglia. In Part 2, we describe available literature on central neuromodulation in primary headaches. Central stimulation targets include vagus nerve and deep brain structures. Part 2 also analyzes overall therapeutic efficacy, safety, cost, patient selection, and recommendations for further research of neurostimulation modalities based on available data.