Activation of Cannabinoid CB2Receptors Suppresses C-Fiber Responses and Windup in Spinal Wide Dynamic Range Neurons in the Absence and Presence of Inflammation

2004 ◽  
Vol 92 (6) ◽  
pp. 3562-3574 ◽  
Author(s):  
A. G. Nackley ◽  
A. M. Zvonok ◽  
A. Makriyannis ◽  
A. G. Hohmann
Keyword(s):  
Electrical Stimulation ◽  
Dorsal Horn ◽  
Dynamic Range ◽  
Transcutaneous Electrical Stimulation ◽  
Wide Dynamic Range ◽  
Spinal Dorsal ◽  
C Fiber ◽  
Wdr Neurons ◽  
Electrophysiological Effects ◽  
Carrageenan Inflammation

Effects of the CB2-selective cannabinoid agonist AM1241 on activity evoked in spinal wide dynamic range (WDR) neurons by transcutaneous electrical stimulation were evaluated in urethane-anesthetized rats. Recordings were obtained in both the absence and the presence of carrageenan inflammation. AM1241, administered intravenously or locally in the paw, suppressed activity evoked by transcutaneous electrical stimulation during the development of inflammation. Decreases in WDR responses resulted from a suppression of C-fiber–mediated activity and windup. Aβ- and Aδ-fiber–mediated responses were not reliably altered. The AM1241-induced suppression of electrically evoked responses was blocked by the CB2antagonist SR144528 but not by the CB1antagonist SR141716A. AM1241 (33 μg/kg intraplantar [ipl]), administered to the carrageenan-injected paw, suppressed activity evoked in WDR neurons relative to groups receiving vehicle in the same paw or AM1241 in the opposite (noninflamed) paw. The electrophysiological effects of AM1241 (330 μg/kg intravenous [iv]) were greater in rats receiving ipl carrageenan compared with noninflamed rats receiving an ipl injection of vehicle. AM1241 failed to alter the activity of purely nonnociceptive neurons recorded in the lumbar dorsal horn. Additionally, AM1241 (330 μg/kg iv and ipl; 33 μg/kg ipl) reduced the diameter of the carrageenan-injected paw. The AM1241-induced decrease in peripheral edema was blocked by the CB2but not by the CB1antagonist. These data demonstrate that activation of cannabinoid CB2receptors is sufficient to suppress neuronal activity at central levels of processing in the spinal dorsal horn. Our findings are consistent with the ability of AM1241 to normalize nociceptive thresholds and produce antinociception in inflammatory pain states.

Transient spinal cord ischemia induces temporary hypersensitivity of dorsal horn wide dynamic range neurons to myelinated, but not unmyelinated, fiber input

1992 ◽  
Vol 68 (2) ◽  
pp. 384-391 ◽  
Author(s):  
J. X. Hao ◽  
X. J. Xu ◽  
Y. X. Yu ◽  
A. Seiger ◽  
Z. Wiesenfeld-Hallin
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Mechanical Stimulation ◽  
Dynamic Range ◽  
Background Activity ◽  
Spinal Cord Ischemia ◽  
Receptive Fields ◽  
Wide Dynamic Range ◽  
C Fiber ◽  
Wdr Neurons

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)

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

1992 ◽  
Vol 68 (2) ◽  
pp. 392-396 ◽  
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).

Peripheral oxytocin receptors inhibit the nociceptive input signal to spinal dorsal horn wide-dynamic-range neurons

Pain ◽  
2017 ◽  
Vol 158 (11) ◽  
pp. 2117-2128 ◽  
Author(s):  
Abimael González-Hernández ◽  
Alfredo Manzano-García ◽  
Guadalupe Martínez-Lorenzana ◽  
Irma A. Tello-García ◽  
Martha Carranza ◽  
...  
Keyword(s):  
Dorsal Horn ◽  
Input Signal ◽  
Spinal Dorsal Horn ◽  
Dynamic Range ◽  
Wide Dynamic Range ◽  
Spinal Dorsal ◽  
Oxytocin Receptors ◽  
Nociceptive Input ◽  
Wide Dynamic Range Neurons

Analysis of Interspike Interval of Dorsal Horn Neurons Evoked by Different Needle Manipulations at St36

2014 ◽  
Vol 32 (1) ◽  
pp. 43-50 ◽  
Author(s):  
Tao Zhou ◽  
Jiang Wang ◽  
Chun-Xiao Han ◽  
Ishida Torao ◽  
Yi Guo
Keyword(s):  
Firing Rate ◽  
Dorsal Horn ◽  
Neural Coding ◽  
Spinal Dorsal Horn ◽  
Interspike Interval ◽  
Dynamic Range ◽  
Stimulus Frequency ◽  
Electrical Signals ◽  
Spinal Dorsal ◽  
Wdr Neurons

Objectives Previous research has suggested that different manual acupuncture (MA) manipulations may have different physiological effects. Recent studies have demonstrated that neural electrical signals are generated or changed when acupuncture is administered. In order to explore the effects of different MA manipulations on the neural system, an experiment was designed to record the discharges of wide dynamic range (WDR) neurons in the spinal dorsal horn evoked by MA at different frequencies (0.5, 1, 2 and 3 Hz) at ST36. Methods Microelectrode extracellular recordings were used to record the discharges of WDR neurons evoked by different MA manipulations. Approximate firing rate and coefficient of variation of interspike interval (ISI) were used to extract the characteristic parameters of the neural electrical signals after spike sorting, and the neural coding of the evoked discharges by different MA manipulations was obtained. Results Our results indicated that the neuronal firing rate and time sequences of ISI showed distinct clustering properties for different MA manipulations, which could distinguish them effectively. Conclusions The combination of firing rate and ISI codes carries information about the acupuncture stimulus frequency. Different MA manipulations appear to change the neural coding of electrical signals in the spinal dorsal horn through WDR neurons.

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