Descending inhibition selectively counteracts the capsaicin-induced facilitation of dorsal horn neurons activated by joint nociceptive afferents

2019 ◽  
Vol 237 (7) ◽  
pp. 1629-1641 ◽  
Author(s):  
A. Ramírez-Morales ◽  
E. Hernández ◽  
P. Rudomin
Keyword(s):  
Dorsal Horn ◽  
Descending Inhibition ◽  
Dorsal Horn Neurons ◽  
Nociceptive Afferents

Midbrain Periaqueductal Gray (PAG) Inhibits Nociceptive Inputs to Sacral Dorsal Horn Nociceptive Neurons Through α2-Adrenergic Receptors

1998 ◽  
Vol 80 (5) ◽  
pp. 2244-2254 ◽  
Author(s):  
Dénes Budai ◽  
Ichiro Harasawa ◽  
Howard L. Fields
Keyword(s):  
Dorsal Horn ◽  
Kainic Acid ◽  
Adrenergic Receptors ◽  
Extracellular Recording ◽  
Periaqueductal Gray ◽  
Descending Inhibition ◽  
Excitatory Effect ◽  
Noxious Heat ◽  
Nociceptive Neurons ◽  
Dorsal Horn Neurons

Budai, Dénes, Ichiro Harasawa, and Howard L. Fields. Midbrain periaqueductal gray (PAG) inhibits nociceptive inputs to sacral dorsal horn nociceptive neurons through α2-adrenergic receptors. J. Neurophysiol. 80: 2244–2254, 1998. Modulation of sacral spinal dorsal horn neurons by the ventrolateral PAG was studied by extracellular recording combined with microiontophoretic applications of α-adrenergic agonists or antagonists. Bicuculline (BIC, 15 ng) microinjected into the ventrolateral PAG produced a consistent inhibition of the responses of nociceptive dorsal horn neurons. After PAG–BIC applications, the total number of spikes per heat stimulation period was significantly decreased to a mean of 37 ± 19% ( n = 8) of the pre-BIC control. Local iontophoresis of the selective α2-adrenoceptor antagonists idazoxan or yohimbine but not the selective α1 antagonist benoxathian significantly reversed PAG–BIC-evoked inhibition. At low ejection currents, clonidine, an α2-adrenoceptor agonist, markedly reduced noxious heat-evoked responses but had no consistent action on the responses to iontophoresed excitatory amino acids [EAA; N-methyl-d-aspartate (NMDA) or kainic acid]. At ejection currents higher than required to block descending inhibition, idazoxan potentiated responses to both heat and EAA iontophoresis. At higher ejection currents, EAA responses were inhibited by clonidine. This indicates that both presynaptic and postsynaptic α2 receptors are capable of inhibiting the recorded neurons. Activation of the α1 adrenoceptors by iontophoresis of methoxamine often led to a marked increase in the responses to kainic acid and, to a lesser extent, to NMDA iontophoresis or noxious heat. Together with previously reported work, the current experiments demonstrate that PAG neurons inhibit nociceptive dorsal horn neurons primarily through an indirect α2 adrenoceptor mechanism. In this same population of dorsal horn neurons, norepinephrine has a direct α1-mediated excitatory effect.

Spinal pathways mediating tonic, coeruleospinal, and raphe-spinal descending inhibition in the rat

1987 ◽  
Vol 58 (1) ◽  
pp. 138-159 ◽  
Author(s):  
S. L. Jones ◽  
G. F. Gebhart
Keyword(s):  
Spontaneous Activity ◽  
Dorsal Horn ◽  
Unit Activity ◽  
Tail Flick ◽  
Descending Inhibition ◽  
Nociceptive Transmission ◽  
Dorsal Horn Neurons ◽  
C Fibers ◽  
Electrophysiological Studies ◽  
Evoked Activity

1. The contribution of midline medullary bulbospinal neurons to descending inhibition from the locus coeruleus (LC) and the funicular trajectories of coeruleo- and raphe-spinal fibers mediating inhibition of spinal nociceptive transmission were examined in different experiments. Extracellular recordings of lumbar dorsal horn neurons were made in deeply pentobarbital-anesthetized, paralyzed rats. All units studied responded to electrical stimulation of the ipsilateral tibial nerve at intensities supramaximal to activate A-alpha-delta- and C-fibers and to mechanical and heat (50 degrees C) stimuli of the glabrous skin of the ipsilateral hind foot. Parallel studies were done in lightly pentobarbital-anesthetized rats utilizing the nociceptive tail-flick (TF) reflex. 2. To examine the contribution of bulbospinal neurons in the nucleus raphe magnus (NRM) to descending coeruleospinal inhibition, lidocaine microinjections were made into the NRM to produce a time-limited, reversible block. Lidocaine microinjections into the NRM effectively blocked NRM stimulation-produced inhibition of the TF reflex (prelidocaine stimulation thresholds were increased two to three times), but did not affect stimulation-produced inhibition from the LC. 3. In parallel electrophysiological studies, stimulation in the NRM inhibited heat-evoked dorsal horn unit activity to 31% of control, whereas stimulation in the LC/SC inhibited heat-evoked activity of the same units to 30% of control. Following NRM lidocaine microinjections, stimulation at the same intensity in the NRM no longer inhibited heat-evoked activity (93% of control), confirming the efficacy of the lidocaine block. LC stimulation-produced inhibition, however, was not affected by blockage of the NRM; heat-evoked unit activity was inhibited by LC stimulation to 39% of control. 4. The effects of ipsilateral and bilateral ventrolateral funiculus (VLF) lidocaine microinjections on spontaneous and heat-evoked unit activity were examined in other experiments. Spontaneous activity increased following ipsilateral VLF lidocaine microinjections for 13/18 units; decreases and no change in spontaneous activity were observed for three and two units, respectively. Heat-evoked unit activity was increased significantly following ipsilateral VLF lidocaine microinjections.(ABSTRACT TRUNCATED AT 400 WORDS)

Tonic descending influences on receptive-field properties of nociceptive dorsal horn neurons in sacral spinal cord of rat

1990 ◽  
Vol 63 (5) ◽  
pp. 1022-1032 ◽  
Author(s):  
J. M. Laird ◽  
F. Cervero
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Intact Animal ◽  
Cervical Spinal Cord ◽  
Afferent Input ◽  
Superficial Dorsal Horn ◽  
Descending Inhibition ◽  
Dorsal Horn Neurons ◽  
C Fiber ◽  
Mechanical Thresholds

1. Single-unit electrical activity has been recorded from 34 dorsal horn neurons in the sacral segments (S1-2) of the spinal cord in halothane-anesthetized rats. All of the neurons had cutaneous receptive fields (RFs) on the rat's tail. The neurons were classified according to their responses to both innocuous and noxious mechanical stimulation of their RFs. Twenty-five cells were driven by both innocuous and noxious skin stimulation (multireceptive or class 2), and 9 neurons were driven only by noxious skin stimulation (nocireceptive or class 3). 2. The RF size, mechanical threshold, and afferent input properties of these neurons were determined in the intact anesthetized and spinalized states. Reversible spinalization was achieved by cooling the cervical spinal cord to 4 degrees C. 3. The class 2 neurons had a mean RF size of 919.8 +/- 112.0 (SE) mm2 in the intact animal. Fourteen of the 25 class 2 cells had larger RFs in the spinal state (mean increase = 330.0 mm2, SE = 79.2) and so were under tonic descending inhibition. Five neurons, all with C-fiber input, had smaller RFs (mean decrease = 247.6 mm2, SE = 136.6) and higher mechanical thresholds in the spinal state and so were under tonic descending excitation. Six neurons were unaffected by spinalization. 4. Five class 3 neurons recorded in the superficial dorsal horn had small RFs in the intact animal (mean = 201.0 mm2, SE = 48.8) and showed little or no change in RF size on spinalization (mean increase = 33.4 mm2, SE = 16.7), but their mechanical thresholds did decrease, indicating weak tonic descending inhibition. In contrast, four class 3 neurons recorded in the deep dorsal horn had larger RFs in the intact animal (mean = 566.8 mm2, SE = 156.8), and were under strong tonic descending inhibition, because they had much larger RFs (mean increase = 461.0 mm2, SE = 68.3), lower mechanical thresholds, and stronger C-fiber afferent input in the spinal state. 5. We conclude that the majority of nociceptive dorsal horn neurons are subject to a net tonic descending control of their RF properties. The class 2 neurons in the deep dorsal horn appear to be a heterogeneous population, some cells being under tonic descending excitation and others under tonic descending inhibition. Class 3 cells can be separated into those located in the superficial dorsal horn, whose RF properties show very little change on spinalization, and those in the deep dorsal horn, whose RF properties change markedly on spinalization.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Neuron-specific spinal cord translatomes reveal a neuropeptide code for mouse dorsal horn excitatory neurons

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rebecca Rani Das Gupta ◽  
Louis Scheurer ◽  
Pawel Pelczar ◽  
Hendrik Wildner ◽  
Hanns Ulrich Zeilhofer
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Functional Organization ◽  
Affinity Purification ◽  
Expression Patterns ◽  
Inhibitory Neurons ◽  
Dorsal Horn Neurons ◽  
Expression Of Genes ◽  
Excitatory Neurons ◽  
Genes Encoding

AbstractThe spinal dorsal horn harbors a sophisticated and heterogeneous network of excitatory and inhibitory neurons that process peripheral signals encoding different sensory modalities. Although it has long been recognized that this network is crucial both for the separation and the integration of sensory signals of different modalities, a systematic unbiased approach to the use of specific neuromodulatory systems is still missing. Here, we have used the translating ribosome affinity purification (TRAP) technique to map the translatomes of excitatory glutamatergic (vGluT2+) and inhibitory GABA and/or glycinergic (vGAT+ or Gad67+) neurons of the mouse spinal cord. Our analyses demonstrate that inhibitory and excitatory neurons are not only set apart, as expected, by the expression of genes related to the production, release or re-uptake of their principal neurotransmitters and by genes encoding for transcription factors, but also by a differential engagement of neuromodulator, especially neuropeptide, signaling pathways. Subsequent multiplex in situ hybridization revealed eleven neuropeptide genes that are strongly enriched in excitatory dorsal horn neurons and display largely non-overlapping expression patterns closely adhering to the laminar and presumably also functional organization of the spinal cord grey matter.

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