Response properties of nociceptive and non-nociceptive neurons in the ratʼs trigeminal subnucleus caudalis (medullary dorsal horn) related to cutaneous and deep craniofacial afferent stimulation and modulation by diffuse noxious inhibitory controls

Pain ◽  
1990 ◽  
Vol 41 (3) ◽  
pp. 331-345 ◽  
Author(s):  
James W. Hu
Keyword(s):  
Dorsal Horn ◽  
Diffuse Noxious Inhibitory Controls ◽  
Afferent Stimulation ◽  
Nociceptive Neurons ◽  
Response Properties ◽  
Medullary Dorsal Horn ◽  
Trigeminal Subnucleus Caudalis

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.

Medullary Dorsal Horn Neuronal Activity in Rats with Persistent Temporomandibular Joint and Perioral Inflammation

1999 ◽  
Vol 82 (3) ◽  
pp. 1244-1253 ◽  
Author(s):  
Koichi Iwata ◽  
Akimasa Tashiro ◽  
Yoshiyuki Tsuboi ◽  
Takao Imai ◽  
Rhyuji Sumino ◽  
...  
Keyword(s):  
Temporomandibular Joint ◽  
Dorsal Horn ◽  
Persistent Pain ◽  
Mechanical Stimuli ◽  
Deep Tissue ◽  
Nociceptive Neurons ◽  
Response Properties ◽  
Medullary Dorsal Horn ◽  
The Mean ◽  
Wdr Neurons

Studies at spinal levels indicate that peripheral tissue or nerve injury induces a state of hyperexcitability of spinal dorsal horn neurons that participates in the development of persistent pain and hyperalgesia. It has not been demonstrated that persistent injury in the orofacial region leads to a similar state of central hyperexcitability in the trigeminal system. The purpose of the present study was to conduct a parametric analysis of the response properties of nociceptive and nonnociceptive neurons in trigeminal nucleus caudalis (medullary dorsal horn, MDH) in a rat model of persistent orofacial inflammation. Neurons were recorded extracellularly and classified as low-threshold mechanoreceptive (LTM, n = 49), wide dynamic range (WDR, n = 82), and nociceptive-specific (NS, n = 11) neurons according to their response properties to mechanical stimuli applied to their cutaneous receptive fields (RFs). The inflammation was induced 24 h before the recordings by injecting complete Freund’s adjuvant (CFA) into the temporomandibular joint (TMJ) capsule or the perioral (PO) skin. The mean areas of the high-threshold RFs of WDR neurons in TMJ (8.66 ± 0.61 cm2, n = 25) and PO (5.61 ± 2.07 cm2, n = 25) inflamed rats were significantly larger than those in naive rats (1.10 ± 0.16 cm2, n = 32). The mean RF size in TMJ-inflamed rats also was significantly larger than that in PO-inflamed rats ( P < 0.01). Furthermore the mean area of the RFs of NS neurons (3.74 ± 1.44 cm2, n = 5) was significantly larger in TMJ inflamed rats as compared with naive rats (0.4 ± 0.09 cm2, n = 3) ( P < 0.05). The background activity in the TMJ- and PO-inflamed rats was generally greater in WDR and NS neurons, but less in LTM neurons, when compared with naive rats. The responses of WDR neurons to noxious mechanical stimuli were increased significantly in TMJ-inflamed rats ( P < 0.05) as compared with naive rats. WDR neuronal responses to mechanical stimulation also were increased in PO-inflamed rats but to a lesser extent than in TMJ-inflamed rats. The injection of CFA into the TMJ or PO skin resulted in reduced responses of LTM neurons to mechanical stimuli. The responses of MDH nociceptive neurons to 48–55°C heating were greater in inflamed rats as compared with naive rats. A subpopulation of WDR neurons recorded from TMJ ( n = 4 of 10)- or PO ( n = 3 of 13)-injected rats responded to cooling in addition to heating of the RFs but did not grade their responses with changes in stimulus intensity. These results indicate that persistent orofacial inflammation produced hyperexcitability of MDH nociceptive neurons. TMJ inflammation resulted in more robust changes in MDH nociceptive neurons as compared with PO inflammation, consistent with previous studies of increased inflammation, increased MDH Fos-protein expression, and increased MDH preprodynorphin mRNA expression in this deep tissue orofacial model of pain and hyperalgesia. The inflammation-induced MDH hyperexcitability may contribute to mechanisms of persistent pain associated with orofacial deep tissue painful conditions.

Response properties of nociceptive neurons in the spinal dorsal horn of aged rat

1998 ◽  
Vol 31 ◽  
pp. S197
Author(s):  
Kenro Kanda ◽  
Koichi Iwata ◽  
Yoshiyuki Tsuboi ◽  
Nobuyuki Shimizu ◽  
Akimasa Tashiro ◽  
...  
Keyword(s):  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Aged Rat ◽  
Nociceptive Neurons ◽  
Response Properties ◽  
Spinal Dorsal

Endomorphin-1 and Endomorphin-2 Modulate Responses of Trigeminal Neurons Evoked by N-Methyl-d-Aspartic Acid and Somatosensory Stimuli

2000 ◽  
Vol 83 (6) ◽  
pp. 3570-3574 ◽  
Author(s):  
Xiao-Min Wang ◽  
Kai-Ming Zhang ◽  
Layron O. Long ◽  
Carmina A. Flores ◽  
Sukhbir S. Mokha
Keyword(s):  
Dorsal Horn ◽  
Opioid Receptor ◽  
Inhibitory Effect ◽  
Noxious Stimulus ◽  
Evoked Responses ◽  
Natural Stimulus ◽  
Nociceptive Neurons ◽  
Medullary Dorsal Horn ◽  
Trigeminal Neurons ◽  
Μ Opioid Receptor

The present study investigated the modulation of N-methyl-d-aspartate (NMDA)-evoked and peripheral cutaneous stimulus-evoked responses of trigeminal neurons by endomorphins, endogenous ligands for the μ-opioid receptor. Effects of endomorphins, administered microiontophoretically, were tested on the responses of nociceptive neurons recorded in the superficial and deeper dorsal horn of the medulla (trigeminal nucleus caudalis) in anesthetized rats. Endomorphin-1 and endomorphin-2 predominantly reduced the NMDA-evoked responses, producing an inhibitory effect of 54.1 ± 2.96% (mean ± SE; n = 34, P < 0.001) in 92% (34/37) of neurons and 63.6 ± 3.61% ( n = 32, P< 0.001) in 91% (32/35) of neurons, respectively. The inhibitory effect of endomorphins was modality specific; noxious stimulus-evoked responses were reduced more than nonnoxious stimulus-evoked responses. Naloxone applied at iontophoretic current that blocked the inhibitory effect of [d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin, reduced the peak inhibitory effect of endomorphins on the NMDA- and natural stimulus-evoked responses. We suggest that endomorphins by acting at μ-opioid receptor selectively modulate noxious stimulus-evoked responses in the medullary dorsal horn.

α2-Adrenoceptors Modulate NMDA-Evoked Responses of Neurons in Superficial and Deeper Dorsal Horn of the Medulla

1998 ◽  
Vol 80 (4) ◽  
pp. 2210-2214 ◽  
Author(s):  
Kai-Ming Zhang ◽  
Xiao-Min Wang ◽  
Angela M. Peterson ◽  
Wen-Yan Chen ◽  
Sukhbir S. Mokha
Keyword(s):  
Dorsal Horn ◽  
Dynamic Range ◽  
Inhibitory Effect ◽  
Male Rats ◽  
Evoked Responses ◽  
Superficial Dorsal Horn ◽  
Nociceptive Neurons ◽  
Adrenoceptor Antagonist ◽  
Medullary Dorsal Horn ◽  
Wdr Neurons

Kai-Ming Zhang, Xiao-Min Wang, Angela M. Peterson, Wen-Yan Chen, and Sukhbir S. Mokha. α2-Adrenoceptors modulate NMDA-evoked responses of neurons in the superficial and deeper dorsal horn of the medulla. J. Neurophysiol. 80: 2210–2214, 1998. Extracellular single unit recordings were made from neurons in the superficial and deeper dorsal horn of the medulla (trigeminal nucleus caudalis) in 21 male rats anesthetized with urethan. NMDA produced an antagonist-reversible excitation of 46 nociceptive as well as nonnociceptive neurons. Microiontophoretic application of a preferential α2-adrenoceptor (α2AR) agonist, (2-[2,6-dichloroaniline]-2-imidazoline) hydrochloride (clonidine), reduced the NMDA-evoked responses of 86% (6/7) of nociceptive-specific (NS) neurons, 82% (9/11) of wide dynamic range (WDR) neurons, and 67% (4/6) of low-threshold (LT) neurons in the superficial dorsal horn. In the deeper dorsal horn, clonidine inhibited the NMDA-evoked responses of 94% (16/17) of NS and WDR neurons and 60% (3/5) of LT neurons. Clonidine facilitated the NMDA-evoked responses in 14% (1/17) of NS, 9% (1/11) of WDR, and 33% (2/6) of LT neurons in the superficial dorsal horn. Idazoxan, an α2AR antagonist, reversed the inhibitory effect of clonidine in 90% (9/10) of neurons, whereas prazosin, an α1-adrenoceptor antagonist with affinity for α2BAR, and α2CAR, were ineffective. We suggest that activation of α2ARs produces a predominantly inhibitory modulation of the NMDA-evoked responses of nociceptive neurons in the medullary dorsal horn.

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

2007 ◽  
Vol 27 (34) ◽  
pp. 9068-9076 ◽  
Author(s):  
C.-Y. Chiang ◽  
J. Wang ◽  
Y.-F. Xie ◽  
S. Zhang ◽  
J. W. Hu ◽  
...  
Keyword(s):  
Dorsal Horn ◽  
Central Sensitization ◽  
Nociceptive Neurons ◽  
Medullary Dorsal Horn

Responses of monkey medullary dorsal horn neurons during the detection of noxious heat stimuli

1989 ◽  
Vol 62 (2) ◽  
pp. 437-449 ◽  
Author(s):  
W. Maixner ◽  
R. Dubner ◽  
D. R. Kenshalo ◽  
M. C. Bushnell ◽  
J. L. Oliveras
Keyword(s):  
Dorsal Horn ◽  
Stimulus Intensity ◽  
Dynamic Range ◽  
Thermal Stimulus ◽  
Mechanical Stimuli ◽  
Behavioral Task ◽  
Noxious Heat ◽  
Nociceptive Neurons ◽  
Medullary Dorsal Horn ◽  
Wdr Neurons

1. We examined the activity of thermally sensitive trigeminothalamic neurons and nonprojection neurons in the medullary dorsal horn (trigeminal nucleus caudalis) in three monkeys performing thermal and visual detection tasks. 2. An examination of neuronal stimulus-response functions, obtained during thermal-detection tasks in which noxious heat stimuli were applied to the face, indicated that wide-dynamic-range neurons (WDR, responsive to innocuous mechanical stimuli with greater responses to noxious mechanical stimuli) could be subclassified based on the slope values of linear regression lines. WDR1 neurons exhibited significantly greater sensitivity to noxious heat stimulation than WDR2 neurons or nociceptive-specific neurons (NS, responsive only to noxious stimuli). 3. In one behavioral task, the monkeys detected 1.0 degrees C increases in noxious heat from preceding noxious heat stimuli ranging from 44 to 48 degrees C. WDR1, WDR2, and NS neurons increased their discharge frequency as a function of the intensity of the first noxious heat temperature (T1) as well as the final temperature (T2). The responses of WDR1 neurons were greater than those produced by WDR2 or NS neurons across all the temperatures examined. The order of stimulus presentation affected the responses of WDR1 neurons to 1.0 degrees C increases in the noxious heat range but not those of WDR2 or NS neurons. 4. In a second behavioral task, the monkeys detected small increases in noxious heat (0.2-0.8 degrees C) from a first temperature of 46 degrees C. Although the responses of all three classes of neurons were monotonically related to stimulus intensity, WDR1 neurons exhibited greater sensitivity to small temperature increases than either WDR2 or NS neurons. 5. Subpopulations of all three classes of neurons exhibited responses that were independent of thermal stimulus parameters or sensory modality and that only occurred during the behavioral task. These task-related responses were time-locked to specific behavioral events associated with trial initiation and trial continuation. 6. These data provide evidence that a subpopulation of WDR neurons is the dorsal horn cell type most sensitive to small increases in noxious heat in the 45-49 degrees C temperature range and provides the most information about stimulus intensity. The findings support the view that nociceptive neurons have the capacity to precisely encode stimulus features in the noxious range and that WDR neurons are likely to participate in the monkeys' ability to perceive the intensity of such stimuli.

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