NF-kappaB inhibition blocks trigeminal pain

Trigeminal NMDA receptors are upregulated via NF-kappaB in response to inflammation

The pain of both TMJ and migraine is mediated through the trigeminal nerve.

NMDA receptors are believed to play a key role in the transmission of pain in the trigeminal.

IL-6 is an important pro-inflammatory cytokine that is under the control of NF-kB.

In the study briefly summarized below:

  • Blocking IL-6 eliminated pain.
  • Blocking NF-kB eliminated pain.
  • Administering IL-6 in the absence of inflammation caused pain.

The implied mechanism of trigeminal pain is inflammation => NF-kB activation => IL-6 production => pain.

By inhibiting NF-kB, both migraine pain and TMJ pain can be effectively treated.

The publication:

January, 2009

Regulation of the trigeminal NR1 subunit expression induced by inflammation of the temporomandibular joint region in rats.

Summary of the abstract

Expression of the N-methyl-d-aspartate (NMDA) receptor in trigeminal nuclei has been shown to play a role in the mechanisms of trigeminal pain.

Here, we examined the hypothesis that the upregulation of the NR1 subunit of the NMDA receptor (NR1) in the trigeminal subnucleus caudalis (Sp5c) following inflammation of the temporomandibular joint (TMJ) region would be regulated by interleukin-6 (IL-6) and the nuclear factor-kappa B (NF-kB).

Once daily intracisternal injection of an IL-6 antiserum or NF-kappaB inhibitor (PDTC) for 6 days, beginning on day 1 immediately after the CFA injection, prevented both the upregulation of NR1 in the ipsilateral Sp5C and pain behavior.

Moreover, once daily intracisternal IL-6 administration for 6 days in naïve rats induced the NR1 upregulation and pain behavior similar to that after TMJ inflammation. These results indicate that the upregulation of IL-6 and NF-kappaB after inflammation of the unilateral TMJ region is a critical regulatory mechanism for the expression of NR1 in the ipsilateral Sp5c, which contributed to the development of TMJ pain behavior in rats.


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