NMDA receptor mechanisms contribute to neuroplasticity induced in caudalis nociceptive neurons by tooth pulp stimulation

We recently demonstrated that application of mustard oil (MO), a small-fiber excitant and inflammatory irritant, to the rat maxillary molar tooth pulp induces significant and prolonged increases in jaw muscle electromyographic (EMG) activity that are suggestive of central neuroplasticity. Because small-fiber afferents, including pulp afferents, access nociceptive neurons in trigeminal (V) subnucleus caudalis, this study examined whether pulpal application of MO induces neuroplastic changes in caudalis nociceptive neurons (wide dynamic range and nociceptive specific) and whether central N-methyl-D-aspartate (NMDA) receptor mechanisms are involved in these MO-induced neuroplastic changes. After pretreatment with vehicle (saline, 10 mu 1 i.t.) to the surface of the medulla, the pulpal application of MO to the maxillary molar tooth gulp produced a significant increase in neuronal spontaneous activity, a significant expansion of the pinch and/or tactile mechanoreceptive field (RF), a significant decrease in mechanical threshold, and significant increases in neuronal responses to graded pinch stimuli. Compared with vehicle-treated rats, pretreatment with the NMDA receptor antagonist MK-801 (10 mu g/10 mu 1 i.t.) followed by MO application to the pulp in another group of rats significantly reduced or abolished these MO-induced neuroplastic changes in nociceptive neurons. In another group of rats pretreated with saline (intrathecally), mineral oil application to the pulp did not show any significant changes in spontaneous activity or RF properties over the 40-min observation period. The pulpal application of MO in other rats (pretreated with saline, intrathecally) did not produce any significant neuroplastic changes in caudalis low-threshold mechanoreceptive neurons. These results indicate that the MO-induced activation of molar pulpal afferents can produce profound NMDA receptor-related neuroplastic changes in caudalis nociceptive neurons. Such neuroplastic changes may contribute to the hyperalgesia and spread of pain that can be associated with pulpal inflammation.