Evidence That Excitatory Amino Acid Receptors within the Temporomandibular Joint Region Are Involved in the Reflex Activation of the Jaw Muscles

Abstract

We have previously shown that injection of the inflammatory irritant and small-fiber excitant mustard oil (MO) into the temporomandibular joint (TMJ) region can reflexively induce a prolonged increase in the activity of both digastric and masseter muscles in rats. It is possible that peripheral excitatory amino acid (EAA) receptors play a role in this effect, because MO-evoked increases in jaw muscle activity are attenuated by preapplication of the noncompetitive NMDA receptor antagonist MK-801 into the TMJ region. In the present study the EAA receptor agonists glutamate, NMDA, kainate, and AMPA were applied locally to the TMJ region. Jaw muscle responses similar to those evoked by MO application to the TMJ region were achieved with glutamate, NMDA, AMPA, and kainate. Repeated application of glutamate, NMDA, or AMPA at intervals of 30 min evoked responses in the ipsilateral jaw muscles that were of comparable magnitude. Co-application of the NMDA receptor antagonist DL-2-amino-5-phosphonovalerate (0.5 micromol) significantly reduced the magnitude of the glutamate- and NMDA-evoked ipsilateral jaw muscle responses without affecting responses evoked by AMPA. In contrast, co-application of the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (1 nmol) significantly reduced the magnitude of the glutamate- and AMPA-evoked ipsilateral jaw muscle responses without affecting responses evoked by NMDA. This evidence suggests that both NMDA and non-NMDA EAA receptor types are located within the TMJ region and may contribute to jaw muscle activity that can be reflexively evoked from the TMJ region.

p-Cymene reduces orofacial nociceptive response in mice

“…Noxious stimulation of primary afferent fibers results in the release of glutamate from the peripheral as well as central terminals of trigeminal and spinal afferent fibers (Keast & Stephensen, 2000;Lam et al, 2005). In addition, glutamate injection into the rat masseter muscle or temporomandibular joint (TMJ) reflexly evokes a dose-dependent increase in jaw muscle electromyographic (EMG) activity (Cairns et al, 1998;Cairns et al, 2001a;Cairns et al, 2001b, Cairns et al, 2002 and central sensitization of trigeminal brainstem nociceptive neurons (Lam et al, 2009b). Similarly, glutamate injection into the human masseter muscle causes pain and mechanical hyperalgesia that may be attenuated by co-injection of a NMDA receptor antagonist (Cairns et al, 1998).…”

Acute and Chronic Craniofacial Pain: Brainstem Mechanisms of Nociceptive Transmission and Neuroplasticity, and Their Clinical Correlates

“…It is also noteworthy that jaw muscle activity, similar to the mustard-oil-evoked EMG activity mentioned above, can also be reflexly evoked by glutamate and NMDA and non-NMDA subtypes applied locally to the TM) region, and that it can be blocked by the local (TM1) application of specific NMDA and non-NMDA antagonists (Yu et al, 1995;Cairns et al, 1998). Analysis of these data clearly indicates that peripheral as well as central excitatory amino acid receptor mechanisms may play a role in this reflex expression of central neuroplasticity.…”

“…and iontophoretic application of NMDA to subnucleus caudalis can modulate the activity of caudalis neurons (Zhang et al, 1996). Furthermore, systemic or local brainstem application of an NMDA antagonist can antagonize corneal-induced c-fos expression in subnucleus caudalis as well as the C-fiber-related activity of oralis nociceptive neurons (Parada et a., 1997) (Cairns et al, 1998; see also Section VII).…”

Neuroinflammation and Comorbidity of Pain and Depression

“…Numerous studies have reported similar effects, such as intraplantar injection of glutamate resulting in decreased mechanical paw withdrawal thresholds in rats via activation of peripheral NMDA, kainate, and AMPA receptors (Jackson et al, 1995). Notably, temporomandibular joint injury models in rats have demonstrated that local administration of glutamate, NMDA, and AMPA activates jaw muscles evidenced by increased electromyographic activity (Cairns et al, 1998). Furthermore, these effects were attenuated under NMDA antagonism.…”