Estrogen plus inflammation act via the trigeminal nerve to increase pain in TMD and perhaps migraine
The highest incidence of TMD is observed in women between 20 and 40.
The authors note that TMD is associated with estrogen. Their investigation concerned the possible mechanism by which estrogen might act as a risk factor in the development of TMD.
They found that inflammation plus estrogen increased pain perception via the trigeminal nerve through a MAPK pathway.
The MAPK pathway does interact with NF-kappaB, but the primary point of interest here is the overlap with migraine. Migraine is predominantly a disease of women (approximately two to three times as many women suffer with migraine as men.) Migraine is also most prevalent between ages 20 and 40. The trigeminal nerve is central in migraine pain.
It may be that migraine and TMD share, at least to some extent, the same underlying pathology.
Estrogen is generally anti-inflammatory and is considered ‘protective’ against certain conditions associated with inflammation (e.g. atherosclerosis.) Nonetheless, many of the conditions most closely associated with inflammation (e.g. autoimmune conditions) are far more common in women.
If the reason for this apparent paradox could be determined, it might be of great assistance in developing effective treatments for conditions associated with inflammation.
Chronic inflammation and estradiol interact through MAPK activation to affect TMD nociceptive processing by trigeminal caudalis neurons.
Summary of the abstract
The mitogen-activated protein kinase and extracellular regulated kinase pathway plays a key role in mediating estrogen actions in the brain and neuronal sensitization during inflammation.
Estrogen status is a risk factor in chronic temporomandibular joint disorders (TMD,) but the basis for this association is not known. The present study investigated a hypothesis that estrogen status acts through a signaling pathway to alter pain sensation (pain processing) in TMD.
These results suggested that estrogen status and chronic inflammation act, at least in part, through a common pathway to enhance TMD pain perception.