The pain lozenge

Migraine mix: CGRP, TNF, NF-kappaB, TMD

High levels of CGRP  are implicated in both TMJ and migraine.

In both temporomandibular joint disorder (TMD) and migraine, high levels of CGRP are found in the trigeminal ganglion. CGRP (calcitonin gene related peptide) is a neuropeptide and its release is associated with neuroinflammation. That inflammation is associated with (leads to) an increase in other pro-inflammatory cytokines.

In the study briefly summarized below, administration of TNF led to an increase in CGRP. While the authors postulate that the MAPK pathway is of greatest importance, NF-kappaB was also shown to be activated. NF-kB activation both results from, and results in, higher levels of TNF. That is, TNF activates NF-kB and activated NF-kB turns on the production of more TNF.

As with most inflammation events, the interaction of the various components is complex and not completely understood. What is clear is that inflammation happens, that it’s important, and that CGRP, NF-kappaB, TNF and the trigeminal ganglion are all involved – both in migraine and in TMJ.

The publication:

January, 2006

Tumor necrosis factor-alpha stimulation of calcitonin gene-related peptide expression and secretion from rat trigeminal ganglion neurons.

Summary of the abstract

CGRP in trigeminal ganglion is implicated in neurovascular headaches and temporomandibular joint disorders.

Elevation of cytokines contributes to the pathology of these diseases.

However, a connection between cytokines and CGRP gene expression in trigeminal ganglion nerves has not been established. We have focused on the effects of the cytokine tumor necrosis factor-alpha (TNF). TNF receptors were found on the majority of CGRP-containing rat trigeminal ganglion neurons. Treatment of cultures with TNF stimulated CGRP secretion.

TNF activated the transcription factor NF-kappaB, as well as other pathways.


One Response to Migraine mix: CGRP, TNF, NF-kappaB, TMD
  1. [...] levels of inflammatory mediators such as TNF, CGRP are seen in the trigeminal in association with [...]