Neuroplasticity Induced by Tooth Pulp Stimulation in Trigeminal Subnucleus Oralis Involves NMDA Receptor Mechanisms

Abstract

We have recently demonstrated that application of the mustard oil (MO), a small-fiber excitant and inflammatory irritant, to the rat maxillary molar tooth pulp induces significant increases in jaw muscle electromyographic (EMG) activity and neuroplastic changes in trigeminal (V) subnucleus caudalis. Since subnucleus oralis (Vo) as well as caudalis receives projections from molar pulp afferents and is also an integral brain stem relay of afferent input from orofacial structures, we tested whether MO application to the exposed pulp induces neuroplastic changes in oralis neurons and whether microinjection of MK-801, a noncompetitive NMDA antagonist, into the Vo influences the pulp/MO-induced neuroplastic changes in chloralose/urethan-anesthetized rats. Single neuronal activity was recorded in Vo, and neurons classified as low-threshold mechanoreceptive (LTM), wide dynamic range (WDR), nociceptive-specific (NS), deep (D), or skin/mucosa and deep (S + D). The spontaneous activity, mechanoreceptive field (RF) size, mechanical threshold, and response to suprathreshold mechanical stimuli applied to the neuronal RF were assessed prior to and throughout a 40- to 60-min period after MO application to the maxillary molar pulp. In animals pretreated with saline microinjection (0.3 microl) into the Vo, MO application to the pulp produced a significant increase in spontaneous activity, expansion of the pinch or deep RF, decrease in the mechanical threshold, and increase in response to suprathreshold mechanical stimuli of the nociceptive (WDR, NS, and S + D) neurons except for those nociceptive neurons having their RF only in the intraoral region. The pulpal application of MO did not produce any significant neuroplastic changes in LTM neurons. Furthermore, in animals pretreated with MK-801 microinjection (3 microg/0.3 microl) into the Vo, MO application to the pulp did not produce any significant changes in the RF and response properties of nociceptive neurons. In other animals pretreated with saline (0.3 microl) or MK-801 (3 microg/0.3 microl) microinjected into the Vo, mineral oil application to the pulp did not produce any significant changes in RF and response properties of nociceptive neurons. These findings indicate that the application of MO to the tooth pulp can induce significant neuroplastic changes in oralis nociceptive neurons and that central NMDA receptor mechanisms may be involved in these neuroplastic changes.

Pharmacological analysis of excitatory and inhibitory synaptic transmission in horizontal brainstem slices preserving three subnuclei of spinal trigeminal nucleus

“…Intersubnuclear communication in trigeminal sensory processing has been examined from various forms of input including facial skin (Dallel et al, 1998;Greenwood and Sessle, 1976;Woda et al, 2001), tooth pulp Hu et al, 2002;Park et al, 2001), ocular surface (Hirata et al, 2003(Hirata et al, , 2004 and dural membranes (Davis and Dostrovsky, 1988). In addition, it has been suggested that central axons of neurons innervating tooth pulp terminate heavier to Vo than Vc (Arvidsson and Gobel, 1981;Marfurt and Turner, 1984;Shigenaga et al, 1986;Takemura et al, 1991Takemura et al, , 1993, and those innervating facial areas primarily to the Vc (Takemura et al, 1987).…”

“…In addition, anatomical (Voisin et al, 2002) or functional Dallel et al, 1998;Hu et al, 1981;Park et al, 2001;Woda et al, 2001) studies have recently demonstrated an ascending connection from Vc to Vo which may be required for C-fiber-mediated nociceptive transmission from Vc to Vo (Pajot et al, 2000). In spite of these studies above, pharmacological analysis of the intersubnuclear synaptic transmission have not been tried yet.…”

Astroglial Glutamate–Glutamine Shuttle Is Involved in Central Sensitization of Nociceptive Neurons in Rat Medullary Dorsal Horn

“…The average spontaneous activity in hertz of a nociceptive neuron was determined over the initial 1 min (for NS neurons) or 5 min (for WDR neurons) recording period. As outlined in our previous studies (Chiang et al, 1998(Chiang et al, , 2005Park et al, 2001;Hu et al, 2002;Xie et al, 2007), the cutaneous mechanoreceptive field (RF) of each WDR neuron was determined by brushing the skin with a force Ͻ2 g; the cutaneous pinch/pressure RF of each NS or WDR neuron was determined through the use of a blunt probe and a pair of nonserrated forceps. A burst response consisting of at least two spikes during each stimulus trial was accepted as the criterion for the RF boundary of the neuron tested.…”

“…For NS neurons, the activation threshold to a mechanical stimulus applied to the orofacial RF was assessed by a pair of forcemonitoring forceps (with an attached strain gauge that monitored force levels up to 600 g/mm 2 ) or an electronic von Frey monofilament, and as the mechanical force was gradually increased, the responses of the tested neuron were monitored and recorded simultaneously by the use of the Spike2 program (CED 1401 plus). The NS neuronal responses to four incremental graded mechanical pinch stimuli with a force-monitoring forceps or graded pressure by means of electronic von Frey monofilament applications (e.g., 20 -25, 40 -50, 60 -80, 100, and even 200 g, delivered in ascending order, each for 5 s at an interval of Ͼ45 s) applied to the neuronal orofacial RF were determined, as described previously (Chiang et al, 1998(Chiang et al, , 2005Park et al, 2001;Hu et al, 2002;Xie et al, 2007). The pinch/pressure-evoked responses of a given neuron were assessed by summing the number of spikes evoked by each of these four graded stimuli.…”

N-methyl-D-aspartate-dependent long-term potentiation of excitatory transmission in trigeminal subnucleus oralis

“…Vsp comprises three subnuclei, that is, oralis (Vo), interpolais (Vi) and caudalis (Vc) in rostrocaudal direction [6], which are interconnected by excitatory and inhibitory synaptic transmission [7][8][9]. Of the intersubnuclear connections, an ascending transmission from Vc to Vo plays an important role in the orofacial nociceptive transmission in the trigeminal system [10][11][12][13][14][15].…”