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 ◽  
...  

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.

2002 ◽  
Vol 88 (4) ◽  
pp. 1614-1624 ◽  
Author(s):  
Bo Hu ◽  
Chen Yu Chiang ◽  
James W. Hu ◽  
Jonathan O. Dostrovsky ◽  
Barry J. Sessle

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.


2002 ◽  
Vol 88 (1) ◽  
pp. 256-264 ◽  
Author(s):  
Chen Yu Chiang ◽  
Bo Hu ◽  
James W. Hu ◽  
Jonathan O. Dostrovsky ◽  
Barry J. Sessle

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.


2007 ◽  
Vol 27 (34) ◽  
pp. 9068-9076 ◽  
Author(s):  
C.-Y. Chiang ◽  
J. Wang ◽  
Y.-F. Xie ◽  
S. Zhang ◽  
J. W. Hu ◽  
...  

Neuroscience ◽  
2013 ◽  
Vol 236 ◽  
pp. 244-252 ◽  
Author(s):  
H. Wang ◽  
Y.F. Xie ◽  
C.Y. Chiang ◽  
J.O. Dostrovsky ◽  
B.J. Sessle

2007 ◽  
Vol 21 (5) ◽  
pp. 634-641 ◽  
Author(s):  
Y.F. Xie ◽  
S. Zhang ◽  
C.Y. Chiang ◽  
J.W. Hu ◽  
J.O. Dostrovsky ◽  
...  

1984 ◽  
Vol 52 (1) ◽  
pp. 39-53 ◽  
Author(s):  
J. W. Hu ◽  
B. J. Sessle

The activity of 160 single neurons excited by electrical stimulation of the canine tooth pulp was studied in the subnucleus caudalis (medullary dorsal horn) and the subnucleus oralis of the trigeminal (V) spinal tract nucleus in chloralose-anesthetized cats to test the effects of natural as well as electrical stimulation of the tooth pulp. The neurons were functionally classified on the basis of their cutaneous receptive-field properties as low-threshold mechanoreceptive (LTM), wide dynamic range (WDR), or nociceptive specific (NS). The orofacial receptive-field properties and responses evoked by electrical stimulation of the tooth pulp indicated that the oralis and caudalis neurons examined had characteristics typical of those previously documented for oralis LTM neurons and for caudalis LTM, WDR, and NS neurons. Each neuron was also tested with cold and warm stimulation of the canine tooth, and some neurons were also tested for responsiveness to thermal stimulation of the premolar tooth or to mechanical and chemical stimuli delivered to the dentine of the canine tooth. Although all the neurons could be excited by electrical stimulation of the pulp, we found that the only neurons that consistently responded to thermal pulp stimuli were those located in the V subnucleus caudalis. Moreover, only those caudalis neurons that had been functionally classified as nociceptive (4 WDR and 21 NS neurons) showed this responsiveness. Heating of the canine or premolar tooth excited 24 of these 25 nociceptive neurons; cooling activated only 3, and none of the small number of neurons tested with mechanical and chemical stimulation of the dentine was excited. The response of the nociceptive neurons to heating of the tooth contrasted with the responses of the same neurons to pinching and heating of their cutaneous receptive field.(ABSTRACT TRUNCATED AT 400 WORDS)


Neuroscience ◽  
2006 ◽  
Vol 142 (3) ◽  
pp. 833-842 ◽  
Author(s):  
S. Zhang ◽  
C.Y. Chiang ◽  
Y.F. Xie ◽  
S.J. Park ◽  
Y. Lu ◽  
...  

Neuroscience ◽  
2011 ◽  
Vol 192 ◽  
pp. 721-731 ◽  
Author(s):  
K. Itoh ◽  
C.-Y. Chiang ◽  
Z. Li ◽  
J.-C. Lee ◽  
J.O. Dostrovsky ◽  
...  

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