INTRODUCTION: Carbon monoxide was previously considered to just be a toxic gas. A wealth of recent information has, however, shown that it is also an important endogenously produced signalling molecule involved in multiple biological processes. Endogenously produced carbon monoxide may thus play an important role in nociceptive processing and in regulation of cerebral arterial tone.

DISCUSSION: Carbon monoxide-induced headache shares many characteristics with migraine and other headaches. The mechanisms whereby carbon monoxide causes headache may include hypoxia, nitric oxide signalling and activation of cyclic guanosine monophosphate pathways. Here, we review the literature about carbon monoxide-induced headache and its possible mechanisms.

CONCLUSION: We suggest, for the first time, that carbon monoxide may play an important role in the mechanisms of migraine and other headaches.