Can Physical Therapies for Chronic Temporomandibular Disorders Cause the Wind-Up of Nociceptive Neurons in the Trigeminal Subnucleus Caudalis?

1. The aim of this study was to test whether parabrachial area (PBA) stimulation exerts inhibitory influences on the spontaneous activity and responses evoked by skin and deep afferent inputs in trigeminal subnucleus caudalis (Vc) neurons, and to compare these effects with those of nucleus raphe magnus (NRM) stimulation. A total of 92 nonnociceptive and nociceptive Vc neurons was recorded in urethan/alpha-chloralose-anesthetized rats. Each neuron was functionally classified as low-threshold mechanoceptive (LTM), wide dynamic range (WDR), nociceptive-specific (NS), nociceptive convergent with both skin and deep inputs (S+D), or deep nociceptive (D); the LTM neurons could be subdivided as rapidly adapting (RA) or slowly adapting (SA). Conditioning stimulation was applied to histologically verified sites in PBA and NRM. 2. The spontaneous or evoked activity of all classes of neurons could be inhibited by PBA as well as by NRM stimulation, but generally the incidence and magnitude of inhibition were lower for the LTM neurons. Occasionally, facilitation of neuronal activity was also produced by PBA and NRM stimulation. 3. The spontaneous activity of 11 LTM neurons (6 RA, 5 SA), 13 nociceptive neurons (6 WDR, 7 NS), and 5 D neurons was tested with stimulation of PBA or NRM or both. LTM spontaneous activity was more significantly inhibited by NRM stimulation than by PBA stimulation, whereas both NRM and PBA stimulation had similar and significant inhibitory effects on NS, WDR, and D neurons. 4. The evoked nonnociceptive responses of 28 LTM neurons (16 RA, 12 SA) and of 6 WDR neurons were also tested with stimulation of PBA or NRM or both. The magnitudes of inhibition of the responses produced by PBA conditioning stimulation were statistically significantly less than those induced by NRM conditioning stimulation. 5. The cutaneous and deep nociceptive responses of cutaneous nociceptive neurons (9 NS, 19 WDR) and seven D neurons, respectively, were also tested with PBA and NRM stimulation. There was a significant difference in potency between PBA- and NRM-induced inhibition, but no difference in the magnitude of inhibitory effects among NS, WDR, and D neurons. For both PBA and NRM conditioning stimulation, graded increases in intensities of stimulation produced linear increases in inhibitory effects on nociceptive responses; an increase in stimulation frequency from 5 to 400 Hz also produced increases in inhibition of the nociceptive responses. 6. In five S+D nociceptive convergent neurons, the responses elicited by deep inputs were more powerfully inhibited by PBA stimulation than those elicited by cutaneous inputs.(ABSTRACT TRUNCATED AT 400 WORDS)

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Effects of a liquid diet on the response properties of temporomandibular joint nociceptive neurons in the trigeminal subnucleus caudalis of growing rats

Orthodontics and Craniofacial Research ◽

10.1111/ocr.12023 ◽

2013 ◽

pp. n/a-n/a ◽

Cited By ~ 1

Author(s):

M. Hiranuma ◽

S. Kokai ◽

K. Fujita ◽

T. Ishida ◽

M. Shibata ◽

...

Keyword(s):

Temporomandibular Joint ◽

Liquid Diet ◽

Nociceptive Neurons ◽

Response Properties ◽

Growing Rats ◽

Trigeminal Subnucleus Caudalis

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

Journal of Neurophysiology ◽

10.1152/jn.00223.2005 ◽

2005 ◽

Vol 94 (3) ◽

pp. 1751-1760 ◽

Cited By ~ 38

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.

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

Journal of Neurophysiology ◽

10.1152/jn.2002.88.4.1614 ◽

2002 ◽

Vol 88 (4) ◽

pp. 1614-1624 ◽

Cited By ~ 51

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.

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NMDA Receptor Involvement in Neuroplastic Changes Induced By Neonatal Capsaicin Treatment in Trigeminal Nociceptive Neurons

Journal of Neurophysiology ◽

10.1152/jn.1997.78.5.2799 ◽

1997 ◽

Vol 78 (5) ◽

pp. 2799-2803 ◽

Cited By ~ 33

Author(s):

Chen Yu Chiang ◽

James W. Hu ◽

Barry J. Sessle

Keyword(s):

Nmda Receptor ◽

Spontaneous Activity ◽

Binding Sites ◽

Nmda Receptor Antagonist ◽

Adult Rats ◽

Nociceptive Neurons ◽

Mk 801 ◽

Medullary Dorsal Horn ◽

C Fiber ◽

Trigeminal Subnucleus Caudalis

Chiang, Chen Yu, James W. Hu, and Barry J. Sessle. NMDA receptor involvement in neuroplastic changes induced by neonatal capsaicin treatment in trigeminal nociceptive neurons. J. Neurophysiol. 78: 2799–2803, 1997. This study examines whether 1) the neonatal loss of C-fiber afferents results in neuroplastic changes in the mechanoreceptive field (RF) properties and spontaneous activity of nociceptive neurons in trigeminal subnucleus caudalis (medullary dorsal horn) of adult rats, and that 2) N-methyl-d-aspartic acid (NMDA) receptor mechanisms are involved in these neuroplastic changes. Compared with vehicle-treated (i.e., control, CON) rats, capsaicin-treated (CAP) rats showed a marked increase in neuronal spontaneous activity and RF size per se, but these neuroplastic changes could be significantly reduced by MK-801 (1 mg/kg, iv), a noncompetitive NMDA receptor antagonist; RF size and spontaneous activity remained unchanged in CON rats after MK-801 administration and in CAP rats after vehicle (saline, iv). Administration of 7-chlorokynurenic acid intrathecally (5 μg/10 μl), an antagonist of strychnine-insensitive glycine binding sites on the NMDA receptor, also significantly reduced neuronal RF size and spontaneous activity in CAP rats, but not in CON rats. These data provide evidence that C-fiber afferents play a role in shaping the properties of nociceptive neurons and that the neuroplastic changes involve NMDA receptor mechanisms.

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