Cholinergic mechanisms of headaches

Headache is one of the widespread pain syndromes with polyneurochemical mechanisms. Here, we review the involvement of the cholinergic neurotransmitter system in the pathophysiology of various forms of headaches. Data on the sources of cholinergic and parasympathetic innervations of intracranial structures and distribution of N- and M-cholinoreceptors of various subtypes within the trigeminovascular system and their roles in the acetylcholine (ACh) effects on brain circulation and processing of nociception in headache are reviewed. We present data on the algogenic and anti-nociceptive effects of ACh in the peripheral and central parts of the trigeminal nerve system and its presumably analgesic effects at the supraspinal level of the CNS. We discuss the ACh-dependent mechanisms of the anticephalalgia action of pharmacological and nonpharmacological approaches that are used for the headache treatment and the future perspectives of the use of cholinergic drugs.