Systemic tocainide relieves mechanical hypersensitivity and normalizes the responses of hyperexcitable dorsal horn wide-dynamic-range neurons after transient spinal cord ischemia in rats

1. The activity of 197 single dorsal horn neurons was recorded extracellularly in the spinal cord of decerebrate, spinalized, unanesthetized rats. The response properties of 174 wide dynamic range (WDR) neurons to electrical, mechanical, and thermal stimulation in three groups of rats were studied:normal, 1-4 days after transient spinal cord ischemia induced photochemically by laser irradiation when the rats exhibited behavioral hypersensitivity to mechanical stimuli (allodynia), and 10-20 days after spinal ischemia when the allodynia had ceased. 2. In normal rats, the responses of dorsal horn WDR neurons to suprathreshold electrical stimulation of their receptive fields consisted of a short-latency (A) and a long-latency (C) response. In 77% of the neurons (57/74), there was a separation between the A- and C-fiber responses. The response threshold (defined as 20% increase in neuronal discharges above background activity) to mechanical stimulation applied with calibrated von Frey hairs was 13.8 g, and the discharges of these neurons to graded stimulation increased linearly. 3. In 68% of WDR neurons in allodynic rats (38/56), the response to suprathreshold electrical stimuli was a single burst with no separation between A- and C-fiber responses. The magnitude and duration of the response were significantly increased compared with those recorded in normal rats. The sensitivity of these neurons to mechanical stimulation was also greatly increased, expressed by a lowered threshold (2.1 +/- 0.3 g, mean +/- SE) and a shift to the left of the nonlinear stimulus-response curve. The background activity of the neurons and the size of the receptive fields were, however, unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

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Baclofen reverses the hypersensitivity of dorsal horn wide dynamic range neurons to mechanical stimulation after transient spinal cord ischemia; implications for a tonic GABAergic inhibitory control of myelinated fiber input

Journal of Neurophysiology ◽

10.1152/jn.1992.68.2.392 ◽

1992 ◽

Vol 68 (2) ◽

pp. 392-396 ◽

Cited By ~ 112

Author(s):

J. X. Hao ◽

X. J. Xu ◽

Y. X. Yu ◽

A. Seiger ◽

Z. Wiesenfeld-Hallin

Keyword(s):

Spinal Cord ◽

Electrical Stimulation ◽

Dorsal Horn ◽

Response Pattern ◽

Dynamic Range ◽

Spinal Cord Ischemia ◽

Mechanical Stimuli ◽

Wide Dynamic Range ◽

Low Intensity ◽

Wdr Neurons

1. In the companion paper, we described a state of hypersensitivity that developed in dorsal horn wide dynamic range (WDR) neurons in rats after transient spinal cord ischemia. Thus the WDR neurons exhibited lower threshold and increased responses to low-intensity mechanical stimuli. The response pattern of these neurons to suprathreshold electrical stimulation was also changed. Notably, the response to A-fiber input was increased. No change in response to thermal stimulation was found before and after spinal cord ischemia. 2. In normal rats, the gamma-aminobutyric acid (GABA)B agonist baclofen (0.1 mg/kg ip) administered 1-3 h before neuronal recording suppressed the responses of WDR neurons to high-intensity mechanical pressure without influencing the threshold and the responses to lower-intensity stimuli. 3. In allodynic rats, similar pretreatment with baclofen totally reversed the hypersensitivity of the WDR neurons to mechanical stimuli and normalized the response pattern of neurons to electrical stimulation. 4. The GABAA receptor agonist muscimol (1 mg/kg ip) did not influence the response of WDR neurons in either normal or allodynic animals. 5. The present results demonstrated that the GABAB agonist baclofen is effective in reversing the hypersensitivity of dorsal horn WDR neurons to low-intensity mechanical stimulation after transient spinal cord ischemia, indicating that dysfunction of the GABAergic inhibitory system may be responsible for the development of neuronal hypersensitivity. 6. It is suggested that GABAergic interneurons exert a tonic presynaptic inhibitory control, through baclofen-sensitive B-type GABA receptors, on input from low-threshold mechanical afferents, and that disruption of this control may result in painful reaction to innocuous stimuli (allodynia).

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Characterization of Wide Dynamic Range Neurons in the Deep Dorsal Horn of the Spinal Cord in Preprotachykinin-A Null Mice In Vivo

Journal of Neurophysiology ◽

10.1152/jn.00945.2003 ◽

2004 ◽

Vol 91 (5) ◽

pp. 1945-1954 ◽

Cited By ~ 11

Author(s):

William J. Martin ◽

YuQing Cao ◽

Allan I. Basbaum

Keyword(s):

Spinal Cord ◽

Dorsal Horn ◽

Dynamic Range ◽

Behavioral Responses ◽

Thermal Stimulus ◽

Wild Type ◽

Wide Dynamic Range ◽

Intensity Coding ◽

Thermal Stimuli ◽

Wide Dynamic Range Neurons

We previously reported that mice with a deletion of the preprotachykinin-A ( pptA) gene, from which substance P (SP) and neurokinin A (NKA) are derived, exhibit reduced behavioral responses to intense stimuli, but that behavioral hypersensitivity after injury is unaltered. To understand the contribution of SP and NKA to nociceptive transmission in the spinal cord, we recorded single-unit activity from wide dynamic range neurons in the lamina V region of the lumbar dorsal horn of urethane-anesthetized wild-type and ppt-A null mutant (–/–) mice. We found that intensity coding to thermal stimuli was largely preserved in the ppt-A –/– mice. Neither the peak stimulus-evoked firing nor the neuronal activity during the initial phase (0–4 s) of the 41–49°C thermal stimuli differed between the genotypes. However, electrophysiological responses during the late phase of the stimulus (5–10 s) and poststimulus (11–25 s) were significantly reduced in ppt-A –/– mice. To activate C-fibers and to sensitize the dorsal horn neurons we applied mustard oil (MO) topically to the hindpaw. We found that neither total MO-evoked activity nor sensitization to subsequent stimuli differed between the wild-type and ppt-A –/– mice. However, the time course of the sensitization and the magnitude of the poststimulus discharges were reduced in ppt-A –/– mice. We conclude that SP and/or NKA are not required for intensity coding or sensitization of nociresponsive neurons in the spinal cord, but that these peptides prolong thermal stimulus-evoked responses. Thus whereas behavioral hypersensitivity after injury is preserved in ppt-A –/– mice, our results suggest that the magnitude and duration of these behavioral responses would be reduced in the absence of SP and/or NKA.

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Rat Dorsal Horn Nociceptive-Specific Neurons Are More Sensitive Than Wide Dynamic Range Neurons to Depression by Immobilizing Doses of Volatile Anesthetics: An Effect Partially Reversed by the Opioid Receptor Antagonist Naloxone

Anesthesia & Analgesia ◽

10.1213/ane.0b013e3181a9770f ◽

2009 ◽

Vol 109 (2) ◽

pp. 641-647 ◽

Cited By ~ 6

Author(s):

Linda S. Barter ◽

Earl E. Carstens ◽

Steven L. Jinks ◽

Joseph F. Antognini

Keyword(s):

Receptor Antagonist ◽

Dorsal Horn ◽

Opioid Receptor ◽

Dynamic Range ◽

Volatile Anesthetics ◽

Wide Dynamic Range ◽

Opioid Receptor Antagonist ◽

Wide Dynamic Range Neurons

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Grouping of somatosensory neurons in the spinal cord and the gracile nucleus of the rat by cluster analysis

Journal of Neurophysiology ◽

10.1152/jn.1994.72.6.2590 ◽

1994 ◽

Vol 72 (6) ◽

pp. 2590-2597 ◽

Cited By ~ 20

Author(s):

J. W. Leem ◽

B. H. Lee ◽

W. D. Willis ◽

J. M. Chung

Keyword(s):

Cluster Analysis ◽

Dorsal Horn ◽

Dynamic Range ◽

High Threshold ◽

Spinothalamic Tract ◽

Wide Dynamic Range ◽

Gracile Nucleus ◽

Noxious Stimuli ◽

Thermal Stimuli ◽

Wide Dynamic Range Neurons

1. A set of 11 cutaneous stimuli defined previously to differentiate among different types of cutaneous sensory receptors in the rat hindpaw was also effective in differentially activating second-order sensory neurons in the dorsal horn and the gracile nucleus of rats. 2. All sampled units were responsive to more than 1 of the 11 stimuli. However, none responded to innocuous warming or cooling stimuli. Therefore further analysis was restricted to responses to nine of the selected stimuli. 3. Cluster analysis of the responses to nine selected innocuous and noxious mechanical stimuli and noxious thermal stimuli yielded seven classes that seemed functionally distinct from each other: a class of high-threshold neurons, three classes of convergent (wide dynamic range) neurons, a class of a mixture of poorly responsive neurons and neurons receiving Pacinian inputs, and two classes of low-threshold neurons. 4. High-threshold neurons responded predominantly to noxious mechanical and thermal stimuli and presumably received an input from both mechanically and thermally sensitive nociceptors. These cells were located in the dorsal horn, and some were spinothalamic tract cells. Wide dynamic range neurons were excited by innocuous and noxious stimuli, but better by noxious stimuli. These classes of cells were either in the dorsal horn (some were spinothalamic tract cells) or in the nucleus gracilis.(ABSTRACT TRUNCATED AT 250 WORDS)

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