Central Sensitization of Nociceptive Neurons in Trigeminal Subnucleus Oralis Depends on Integrity of Subnucleus Caudalis

2002 ◽  
Vol 88 (1) ◽  
pp. 256-264 ◽  
Author(s):  
Chen Yu Chiang ◽  
Bo Hu ◽  
James W. Hu ◽  
Jonathan O. Dostrovsky ◽  
Barry J. Sessle
Keyword(s):  
Brain Stem ◽  
Central Sensitization ◽  
Mustard Oil ◽  
Tooth Pulp ◽  
Nociceptive Neurons ◽  
Response Properties ◽  
Functional Integrity ◽  
Anesthetized Rats ◽  
Noxious Stimuli

Our recent studies have shown that application to the tooth pulp of the inflammatory irritant mustard oil (MO) produces a prolonged (>40 min) “central sensitization” reflected in neuroplastic changes in the mechanoreceptive field (RF) and response properties of nociceptive brain stem neurons in subnuclei oralis (Vo) and caudalis (Vc) of the trigeminal spinal tract nucleus. In view of the previously demonstrated ascending modulatory influence of Vc on Vo, our aim was to determine whether the Vo neuroplastic changes induced by MO application to the tooth pulp depend on an ascending influence from Vc. In chloralose/urethan-anesthetized rats, MO application to the pulp produced significant increases in Vo nociceptive neuronal orofacial RF size and responses to mechanical noxious stimuli that lasted as long as 40–60 min. These changes were not affected by vehicle (saline) microinjected into Vc at 20 min after MO application, but 0.3 μl of a 5 mM CoCl2 solution microinjected into the ipsilateral Vc produced a reversible blockade of the MO-induced Vo neuroplastic changes. A similar volume and concentration of CoCl2 solution injected into subnucleus interpolaris of the trigeminal spinal tract nucleus did not affect the MO-induced neuroplastic changes in Vo. These findings indicate that inflammatory pulp-induced central sensitization in Vo is dependent on the functional integrity of Vc.

Differential effects of cutaneous and deep application of inflammatory irritant on mechanoreceptive field properties of trigeminal brain stem nociceptive neurons

1993 ◽  
Vol 70 (4) ◽  
pp. 1704-1707 ◽  
Author(s):  
X. M. Yu ◽  
B. J. Sessle ◽  
J. W. Hu
Keyword(s):  
Brain Stem ◽  
Mustard Oil ◽  
Facial Skin ◽  
Nociceptive Neurons ◽  
Differential Effects ◽  
Tongue Muscle ◽  
Anesthetized Rats ◽  
Small Fiber ◽  
Afferent Inputs ◽  
Functional Neuroplasticity

1. The aim of this study was to determine whether there are differential neuroplastic effects of cutaneous and deep stimuli on the mechanoreceptive field (RF) properties of nociceptive brain stem neurons recorded in trigeminal (V) subnucleus caudalis. 2. A total of 31 caudalis neurons were functionally identified in anesthetized rats as nociceptive neurons receiving convergent cutaneous and deep afferent inputs, and the effects of the small-fiber excitant and inflammatory irritant mustard oil applied to either tongue muscle or facial skin were tested on their cutaneous and deep RFs. 3. The expression of neuroplasticity on the cutaneous and deep RFs of the neurons was found to depend on the site of application of this irritant. Mustard oil injected into the tongue muscle produced a significant and reversible expansion of both the cutaneous and deep RFs. In contrast, application of mustard oil to facial skin resulted in a significant and reversible expansion of the cutaneous RF, but no deep RF expansion occurred. 4. These findings suggest that considerable functional neuroplasticity of the cutaneous and deep RF properties of V nociceptive neurons can be induced by a peripheral inflammatory irritant and that deep inputs are especially effective in evoking these neuroplastic changes.

Endogenous ATP Involvement in Mustard-Oil-Induced Central Sensitization in Trigeminal Subnucleus Caudalis (Medullary Dorsal Horn)

2005 ◽  
Vol 94 (3) ◽  
pp. 1751-1760 ◽  
Author(s):  
C. Y. Chiang ◽  
S. Zhang ◽  
Y. F. Xie ◽  
J. W. Hu ◽  
J. O. Dostrovsky ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Dorsal Horn ◽  
Central Sensitization ◽  
P2x Receptor ◽  
Field Size ◽  
Mustard Oil ◽  
Tooth Pulp ◽  
Nociceptive Neurons ◽  
Medullary Dorsal Horn ◽  
Trigeminal Subnucleus Caudalis

Central sensitization represents a sustained hypersensitive state of dorsal horn nociceptive neurons that can be evoked by peripheral inflammation or injury to nerves and tissues. It reflects neuroplastic changes such as increases in neuronal spontaneous activity, receptive field size, and responses to suprathreshold stimuli and a decrease in activation threshold. We recently demonstrated that purinergic receptor mechanisms in trigeminal subnucleus caudalis (Vc; medullary dorsal horn) are also involved in the initiation and maintenance of central sensitization in brain stem nociceptive neurons of trigeminal subnucleus oralis. The aim of the present study was to investigate whether endogenous ATP is involved in the development of central sensitization in Vc itself. The experiments were carried out on urethan/α-chloralose anesthetized and immobilized rats. Single neurons were recorded and identified as nociceptive-specific (NS) in the deep laminae of Vc. During continuous saline superfusion (0.6 ml/h it) over the caudal medulla, Vc neuronal central sensitization was readily induced by mustard oil application to the tooth pulp. However, this mustard-oil-induced central sensitization could be completely blocked by continuous intrathecal superfusion of the wide-spectrum P2X receptor antagonist pyridoxal-phosphate-6-azophenyl-2, 4-disulphonic acid tetra-sodium (33–100 μM) and by apyrase (an ectonucleotidase enzyme, 30 units/ml). Superfusion of the selective P2X1, P2X3 and P2X2/3 receptor antagonist 2′,3′- O-(2,4,6-trinitrophenyl) adenosine 5′-triphosphate (6–638 μM) partially blocked the Vc central sensitization. The two P2X receptor antagonists did not significantly affect the baseline nociceptive properties of the Vc neurons. These findings implicate endogenous ATP as an important mediator contributing to the development of central sensitization in nociceptive neurons of the deep laminae of the dorsal horn.

scholarly journals P2X Receptors in Trigeminal Subnucleus Caudalis Modulate Central Sensitization in Trigeminal Subnucleus Oralis

2002 ◽  
Vol 88 (4) ◽  
pp. 1614-1624 ◽  
Author(s):  
Bo Hu ◽  
Chen Yu Chiang ◽  
James W. Hu ◽  
Jonathan O. Dostrovsky ◽  
Barry J. Sessle
Keyword(s):  
Central Sensitization ◽  
Receptor Agonist ◽  
P2x Receptors ◽  
Field Size ◽  
Mustard Oil ◽  
Tooth Pulp ◽  
Receptor Subtypes ◽  
Mechanical Stimuli ◽  
Nociceptive Neurons ◽  
Trigeminal Subnucleus Caudalis

This study investigated the role of trigeminal subnucleus caudalis (Vc) P2X receptors in the mediation of central sensitization induced in nociceptive neurons in subnucleus oralis (Vo) by mustard oil (MO) application to the tooth pulp in anesthetized rats. MO application produced a long-lasting central sensitization reflected in neuroplastic changes (i.e., increases in neuronal mechanoreceptive field size and responses to innocuous and noxious mechanical stimuli) in Vo nociceptive neurons. Twenty minutes after MO application, the intrathecal (i.t.) administration to the rostral Vc of the selective P2X1, P2X3, and P2X2/3 receptor antagonist, 2′-(or 3′-) O-trinitrophenyl-ATP (TNP-ATP), significantly and reversibly attenuated the MO-induced central sensitization for more than 15 min; saline administration had no effect. Administration to the rostral Vc of the selective P2X1, P2X3, and P2X2/3 receptor agonist, α,β-methylene ATP (α,β-meATP, i.t.) produced abrupt and significant neuroplastic changes in Vo nociceptive neurons, followed by neuronal desensitization as evidenced by the ineffectiveness of a second i.t. application of α,β-meATP and subsequent MO application to the pulp. Administration to the rostral Vc of the selective P2X1 receptor agonist β,γ-methylene ATP (β,γ-meATP, i.t.) produced no significant neuroplastic changes per se and did not affect the subsequent MO-induced neuroplastic changes in Vo nociceptive neurons. These results suggest that P2X3 and possibly also the P2X2/3 receptor subtypes in Vc may play a role in the initiation and maintenance of central sensitization in Vo nociceptive neurons induced by MO application to the pulp.

Central sensitization in thalamic nociceptive neurons induced by mustard oil application to rat molar tooth pulp

Neuroscience ◽  
2006 ◽  
Vol 142 (3) ◽  
pp. 833-842 ◽  
Author(s):  
S. Zhang ◽  
C.Y. Chiang ◽  
Y.F. Xie ◽  
S.J. Park ◽  
Y. Lu ◽  
...  
Keyword(s):  
Central Sensitization ◽  
Molar Tooth ◽  
Mustard Oil ◽  
Tooth Pulp ◽  
Nociceptive Neurons ◽  
Rat Molar

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

2001 ◽  
Vol 85 (5) ◽  
pp. 1836-1846 ◽  
Author(s):  
Soo Joung Park ◽  
Chen Yu Chiang ◽  
James W. Hu ◽  
Barry J. Sessle
Keyword(s):  
Nmda Receptor ◽  
Spontaneous Activity ◽  
Emg Activity ◽  
Tooth Pulp ◽  
Mechanical Stimuli ◽  
Nociceptive Neurons ◽  
Mk 801 ◽  
Response Properties ◽  
Mechanical Threshold ◽  
Maxillary Molar

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 μl) 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 μg/0.3 μl) 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 μl) or MK-801 (3 μg/0.3 μl) 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.

scholarly journals NMDA Receptor Mechanisms Contribute to Neuroplasticity Induced in Caudalis Nociceptive Neurons by Tooth Pulp Stimulation

1998 ◽  
Vol 80 (5) ◽  
pp. 2621-2631 ◽  
Author(s):  
Chen Yu Chiang ◽  
Soo Joung Park ◽  
Chun L. Kwan ◽  
James W. Hu ◽  
Barry J. Sessle
Keyword(s):  
Nmda Receptor ◽  
Spontaneous Activity ◽  
Dynamic Range ◽  
Molar Tooth ◽  
Mustard Oil ◽  
Emg Activity ◽  
Tooth Pulp ◽  
Nociceptive Neurons ◽  
Small Fiber ◽  
Maxillary Molar

Chiang, Chen Yu, Soo Joung Park, Chun L. Kwan, James W. Hu, and Barry J. Sessle. NMDA receptor mechanisms contribute to neuroplasticity induced in caudalis nociceptive neurons by tooth pulp stimulation. J. Neurophysiol. 80: 2621–2631, 1998. 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 μl i.t.) to the surface of the medulla, the pulpal application of MO to the maxillary molar tooth pulp 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 μg/10 μl 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.

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