| Summary: | Myofascial temporomandibular disorders (TMD) are common chronic craniofacial
conditions that are characterized by pain in the masseter muscle. It has been suggested
that nerve growth factor (NGF) may contribute to muscle sensitization in TMD-like pain
based on various animal and human studies. Injection of NGF into the masseter muscle
of healthy human subjects is not painful but does induce a localized, quick onset (~1 hour)
and long lasting mechanical sensitization. It is not known how NGF causes this
sensitization.
NGF binds to the p75 receptor as well as the tyrosine kinase receptor A (TrkA), both of
which are expressed on nociceptive neurons and may increase excitability and neuron
sensitization. NGF is also reported to enhance NMDA receptor function on ganglion
excitatory synaptic transmission.
I hypothesized that human NGF mechanically sensitizes masseter muscle nociceptors
by increasing the sensitivity of peripheral NMDA receptors. Co-expression of the
NR2B subunit of the NMDA receptor with P75 and TrkA NGF receptors by trigeminal
ganglia neurons that innervate the masseter muscle was investigated
immunohistochemically. Nociceptor activity was recorded extracellularly from the trigeminal
ganglion of anaesthetized female rats. Nociceptor mechanical threshold was
assessed before and every 30 minutes for 3 hours after injection of human NGF (25
µg/ml, 10 µl), and in subsequent experiments NGF with TrkA or P75 receptor antibodies.
Glutamate (1 M, 10 µl), a NMDA receptor agonist, was injected at the end of each
experiment. Approximately 85% of NR2B positive masseter ganglion neurons
co-expressed P75 or TrkA receptors, suggesting the potential for interaction. When
compared with the vehicle control, it was found that injection of NGF into the masseter
muscle did not evoke significant nociceptor discharge but did significantly reduce
nociceptor mechanical threshold. There was no effect of NGF on glutamate-evoked
nociceptor discharge or glutamate-induced mechanical sensitization. Additional
experiments indicated that NGF-induced mechanical sensitization could be partially
attenuated by co-administration of TrkA receptor antibodies, but not P75 receptor
antibodies. These findings indicate that human NGF-induced sensitization of masseter
nociceptors results, in part, from activation of TrkA receptors but does not appear to be
mediated through enhanced peripheral NMDA receptor activity.
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