Selective Cannabinoid CB1 Receptor Activation Inhibits Spinal Nociceptive Transmission In Vivo

2001 ◽  
Vol 86 (6) ◽  
pp. 3061-3064 ◽  
Author(s):  
Sara Kelly ◽  
Victoria Chapman
Keyword(s):  
Dorsal Horn ◽  
Receptor Activation ◽  
Evoked Responses ◽  
Somatosensory Processing ◽  
Sprague Dawley ◽  
Nociceptive Transmission ◽  
Dorsal Horn Neurons ◽  
Anesthetized Rats ◽  
C Fiber

Cannabinoid1 (CB1) receptors are located at CNS sites, including the spinal cord, involved in somatosensory processing. Analgesia is one of the tetrad of behaviors associated with cannabinoid agonists. Here, effects of a potent cannabinoid CB1 receptor agonist arachidonyl-2-chloroethylamide (ACEA) on evoked responses of dorsal horn neurons in anesthetized rats were investigated. Extracellular recordings of convergent dorsal horn neurons were made in halothane anesthetized Sprague-Dawley rats ( n = 16). Effects of spinal application of ACEA on electrically evoked responses of dorsal horn neurons were studied. Mean maximal effects of 0.5, 5, 50, and 500 ng/50 μl ACEA on the C-fiber-mediated postdischarge response were 79 ± 6, 62 ± 10, and 54 ± 7% ( P < 0.01), 45 ± 6% ( P < 0.01), of control, respectively. ACEA (500 ng/50 μl) also reduced the C-fiber-evoked nonpotentiated responses of neurons (59 ± 9% of control, P < 0.05) and Aδ-fiber-evoked responses of neurons (68 ± 10% of control, P < 0.01). Minor effects of ACEA on Aβ-fiber-evoked responses were observed. Spinal pre-administration of the selective CB1 receptor antagonist SR141716A (0.01 μg/50 μl) significantly reduced effects of ACEA (500 ng/50 μl) on postdischarge responses of dorsal horn neurons. This study demonstrates that spinal CB1 receptors modulate the transmission of C- and Aδ-fiber-evoked responses in anesthetized rats; this may reflect pre- and/or postsynaptic effects of cannabinoids on nociceptive transmission. CB1 receptors inhibit synaptic release of glutamate in rat dorsolateral striatum, a similar mechanism of action may underlie the effects of ACEA on noxious evoked responses of spinal neurons reported here.

Opioids modulate N-methyl-D-aspartic acid (NMDA)-evoked responses of trigeminothalamic neurons

1996 ◽  
Vol 76 (3) ◽  
pp. 2093-2096 ◽  
Author(s):  
X. M. Wang ◽  
S. S. Mokha
Keyword(s):  
Nmda Receptor ◽  
Dorsal Horn ◽  
Aspartic Acid ◽  
Opioid Receptor ◽  
Receptor Agonist ◽  
Receptor Activation ◽  
Evoked Responses ◽  
Nociceptive Neurons ◽  
Nociceptive Transmission ◽  
Opioid Receptor Agonist

1. The present study investigated opioid-mediated modulation of N-methyl-D-aspartic acid (NMDA)-evoked responses of trigeminothalamic neurons in the superficial and deeper dorsal horn of the medulla (trigeminal nucleus caudalis) in rats anesthetized with urethane. 2. Microiontophoretic application of NMDA activated 18/19 trigeminothalamic neurons. Administration of [D-Ala2, N-Me-Phe4,Gly5-ol]-Enkephalin, a selective mu-opioid receptor agonist, reduced the NMDA-evoked responses in 77% of trigeminothalamic neurons. [D-Pen2,5]-Enkephalin, a selective delta-opioid receptor agonist, produced inhibition of NMDA-evoked responses in 36% of neurons. 3. We suggest that 1) NMDA-receptor activation excites trigeminothalamic nociceptive neurons and may, therefore, mediate nociceptive transmission in the medullary dorsal horn; and 2) the predominantly inhibitory modulation of NMDA-receptor-mediated responses of nociceptive trigeminothalamic neurons by activation of mu- and delta-opioid receptors may provide a neural mechanism for the antinociceptive actions of opioids.

scholarly journals Spinal Allografts of Adrenal Medulla Block Nociceptive Facilitation in the Dorsal Horn

2001 ◽  
Vol 85 (4) ◽  
pp. 1788-1792 ◽  
Author(s):  
Ian D. Hentall ◽  
Brian R. Noga ◽  
Jacqueline Sagen
Keyword(s):  
Dorsal Horn ◽  
Adrenal Medulla ◽  
Dynamic Range ◽  
Striated Muscle ◽  
Facilitatory Effect ◽  
Formalin Injection ◽  
Neurophysiological Mechanism ◽  
Dorsal Horn Neurons ◽  
C Fiber

Transplantation of chromaffin cells into the lumbar subarachnoid space has been found to produce analgesia, most conspicuously against chronic neuropathic pain. To ascertain the neurophysiological mechanism, we recorded electrical activity from wide-dynamic-range dorsal horn neurons in vivo, measuring the short-lasting homosynaptic facilitatory effect known as windup, which is induced by repetitive C-fiber input. Rats were given adrenal medulla allografts, or, as controls, striated-muscle allografts. The adrenal-transplanted rats showed analgesia 3–4 wk after transplantation, measured as a reduction in flinching reflexes 30–55 min after subcutaneous formalin injection. Recordings were made under halothane anesthesia, 3–7 days following the behavioral testing. The average C-fiber response and subsequent afterdischarge were facilitated severalfold in control rats by 1-Hz cutaneous electrical stimulation. Such facilitation was essentially absent in adrenal-transplanted animals and also in the A-fiber response of both preparations. Extirpation of transplanted tissue several hours prior to recording did not significantly affect this difference. In conclusion, the adrenal transplants block short-term spinal nociceptive facilitation, probably by stimulating some persistent cellular process that may be an important determinant, but not the only one, of their analgesic effect.

306 IN VIVO IMAGING OF Ca 2+ GRADIENTS IN SPINAL DORSAL HORN NEURONS

2009 ◽  
Vol 13 (S1) ◽  
Author(s):  
M. Gassner ◽  
M. Wagner ◽  
H. Fischer ◽  
R. Drdla ◽  
T. Jäger ◽  
...  
Keyword(s):  
Dorsal Horn ◽  
In Vivo Imaging ◽  
Spinal Dorsal Horn ◽  
Dorsal Horn Neurons ◽  
Spinal Dorsal ◽  
Spinal Dorsal Horn Neurons

Spinal substance P release in vivo during the induction of long-term potentiation in dorsal horn neurons

Pain ◽  
2002 ◽  
Vol 96 (1) ◽  
pp. 49-55 ◽  
Author(s):  
Abdullahi Warsame Afrah ◽  
Atle Fiskå ◽  
Johannes Gjerstad ◽  
Henrik Gustafsson ◽  
Arne Tjølsen ◽  
...  
Keyword(s):  
Substance P ◽  
Dorsal Horn ◽  
Long Term Potentiation ◽  
Dorsal Horn Neurons ◽  
P Release ◽  
Term Potentiation ◽  
Substance P Release

Developmental Changes in the Fidelity and Short-Term Plasticity of GABAergic Synapses in the Neonatal Rat Dorsal Horn

2008 ◽  
Vol 99 (6) ◽  
pp. 3144-3150 ◽  
Author(s):  
Rachel A. Ingram ◽  
Maria Fitzgerald ◽  
Mark L. Baccei
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Receptive Fields ◽  
Neuronal Firing ◽  
Neonatal Rat ◽  
Superficial Dorsal Horn ◽  
Short Term ◽  
Dorsal Horn Neurons ◽  
Gabaergic Synapses

The lower thresholds and increased excitability of dorsal horn neurons in the neonatal rat suggest that inhibitory processing is less efficient in the immature spinal cord. This is unlikely to be explained by an absence of functional GABAergic inhibition because antagonism of γ-aminobutyric acid (GABA) type A receptors augments neuronal firing in vivo from the first days of life. However, it is possible that more subtle deficits in GABAergic signaling exist in the neonate, such as decreased reliability of transmission or greater depression during repetitive stimulation, both of which could influence the relative excitability of the immature spinal cord. To address this issue we examined monosynaptic GABAergic inputs onto superficial dorsal horn neurons using whole cell patch-clamp recordings made in spinal cord slices at a range of postnatal ages (P3, P10, and P21). The amplitudes of evoked inhibitory postsynaptic currents (IPSCs) were significantly lower and showed greater variability in younger animals, suggesting a lower fidelity of GABAergic signaling at early postnatal ages. Paired-pulse ratios were similar throughout the postnatal period, whereas trains of stimuli (1, 5, 10, and 20 Hz) revealed frequency-dependent short-term depression (STD) of IPSCs at all ages. Although the magnitude of STD did not differ between ages, the recovery from depression was significantly slower at immature GABAergic synapses. These properties may affect the integration of synaptic inputs within developing superficial dorsal horn neurons and thus contribute to their larger receptive fields and enhanced afterdischarge.

scholarly journals Regulating nociceptive transmission by VGluT2-expressing spinal dorsal horn neurons

2018 ◽  
Vol 147 (4) ◽  
pp. 526-540 ◽  
Author(s):  
Li Wang ◽  
Shao-Rui Chen ◽  
Huijie Ma ◽  
Hong Chen ◽  
Walter N. Hittelman ◽  
...  
Keyword(s):  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Nociceptive Transmission ◽  
Dorsal Horn Neurons ◽  
Spinal Dorsal ◽  
Spinal Dorsal Horn Neurons

scholarly journals Noradrenaline modulates mechanically evoked responses in the rat spinal dorsal horn: an in vivo patch-clamp study

2019 ◽  
Vol Volume 12 ◽  
pp. 1269-1278 ◽  
Author(s):  
Motoki Sonohata ◽  
Atsushi Doi ◽  
Toshiharu Yasaka ◽  
Daisuke Uta ◽  
Masaaki Mawatari ◽  
...  
Keyword(s):  
Patch Clamp ◽  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Evoked Responses ◽  
Spinal Dorsal ◽  
Clamp Study
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