scholarly journals Presynaptic Inhibition of Pain and Touch in the Spinal Cord: From Receptors to Circuits

2021 ◽  
Vol 22 (1) ◽  
pp. 414
Author(s):  
Antonella Comitato ◽  
Rita Bardoni
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Sensory Information ◽  
Spinal Cord Dorsal Horn ◽  
Primary Afferent ◽  
Dorsal Horn Neurons ◽  
Afferent Fibers ◽  
Peptide Release ◽  
Spinal Cord Dorsal ◽  
Primary Afferent Fibers

Sensory primary afferent fibers, conveying touch, pain, itch, and proprioception, synapse onto spinal cord dorsal horn neurons. Primary afferent central terminals express a wide variety of receptors that modulate glutamate and peptide release. Regulation of the amount and timing of neurotransmitter release critically affects the integration of postsynaptic responses and the coding of sensory information. The role of GABA (γ-aminobutyric acid) receptors expressed on afferent central terminals is particularly important in sensory processing, both in physiological conditions and in sensitized states induced by chronic pain. During the last decade, techniques of opto- and chemogenetic stimulation and neuronal selective labeling have provided interesting insights on this topic. This review focused on the recent advances about the modulatory effects of presynaptic GABAergic receptors in spinal cord dorsal horn and the neural circuits involved in these mechanisms.

ATP P2× Receptors and Sensory Synaptic Transmission Between Primary Afferent Fibers and Spinal Dorsal Horn Neurons in Rats

1998 ◽  
Vol 80 (6) ◽  
pp. 3356-3360 ◽  
Author(s):  
Ping Li ◽  
Amelita A. Calejesan ◽  
Min Zhuo
Keyword(s):  
Spinal Cord ◽  
Synaptic Transmission ◽  
Dorsal Horn ◽  
Lumbar Spinal Cord ◽  
Superficial Dorsal Horn ◽  
Primary Afferent ◽  
Dorsal Horn Neurons ◽  
Afferent Fibers ◽  
Primary Afferent Fibers ◽  
Lumbar Spinal

Li, Ping, Amelita A. Calean, and Min Zhuo. ATP P2× receptors and sensory synaptic transmission between primary afferent fibers and spinal dorsal horn neurons in rats. J. Neurophysiol. 80: 3356–3360, 1998. Glutamate is a major fast transmitter between primary afferent fibers and dorsal horn neurons in the spinal cord. Recent evidence indicates that ATP acts as another fast transmitter at the rat cervical spinal cord and is proposed to serve as a transmitter for nociception and pain. Sensory synaptic transmission between dorsal root afferent fibers and neurons in the superficial dorsal horn of the lumbar spinal cord were examined by whole cell patch-clamp recording techniques. Experiments were designed to test if ATP could serve as a transmitter at the lumbar spinal cord. Monosynaptic excitatory postsynaptic currents (EPSCs) were completely abolished after the blockade of both glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate and N-methyl-d-aspartate receptors. No residual current was detected, indicating that glutamate but not ATP is a fast transmitter at the dorsal horn of the lumbar spinal cord. Pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS), a selective P2× receptor antagonist, produced an inhibitory modulatory effect on fast EPSCs and altered responses to paired-pulse stimulation, suggesting the involvement of a presynaptic mechanism. Intrathecal administration of PPADS did not produce any antinociceptive effect in two different types of behavioral nociceptive tests. The present results suggest that ATP P2×2 receptors modulate excitatory synaptic transmission in the superficial dorsal horn of the lumbar spinal cord by a presynaptic mechanism, and such a mechanism does not play an important role in behavioral responses to noxious heating. The involvement of other P2× subtype receptors, which is are less sensitive to PPADS, in acute nociceptive modulation and persistent pain remains to be investigated.

Microglial refinement of spinal cord sensory circuitry regulates normal maturation of dynamic touch.

2021 ◽  
Author(s):  
Yajing Xu ◽  
Stephanie Koch ◽  
Alexander Chamessian ◽  
Qianru He ◽  
Mayya Sundukova ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Normal Development ◽  
Physiological Role ◽  
Spinal Cord Dorsal Horn ◽  
Dynamic Touch ◽  
Tactile Sensitivity ◽  
Primary Afferent ◽  
Spinal Cord Dorsal

In the spinal cord dorsal horn, sensory circuits undergo remarkable postnatal reorganisation, including refinement of primary afferent A-fibres in the superficial layers, accompanied by decreased cutaneous sensitivity. Here we show a physiological role of microglia necessary for normal development of dorsal horn sensory circuits and tactile sensitivity. In the absence of microglial engulfment, superfluous A-fibre projections persist, leading to lifelong hypersensitivity to dynamic touch.

Synergistic Enhancement of Glutamate-Mediated Responses by Serotonin and Forskolin in Adult Mouse Spinal Dorsal Horn Neurons

2002 ◽  
Vol 87 (2) ◽  
pp. 732-739 ◽  
Author(s):  
Guo-Du Wang ◽  
Min Zhuo
Keyword(s):  
Spinal Cord ◽  
Nmda Receptors ◽  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Adult Mouse ◽  
Dorsal Horn Neurons ◽  
Spinal Dorsal ◽  
Afferent Fibers ◽  
Primary Afferent Fibers ◽  
Spinal Dorsal Horn Neurons

Glutamate is the major excitatory amino acid neurotransmitter in the CNS, including the neocortex, hippocampus, and spinal cord. Normal synaptic transmission is mainly mediated by glutamate AMPA and/or kainate receptors. Glutamate N-methyl-d-aspartate (NMDA) receptors are normally inactive and only activated when a sufficient postsynaptic depolarization is induced by the activity. Here we show that in sensory synapses of adult mouse, some synaptic responses (26.3% of a total of 38 experiments) between primary afferent fibers and dorsal horn neurons are almost completely mediated by NMDA receptors. Dorsal root stimulation did not elicit any detectable AMPA/kainate receptor-mediated responses in these synapses. Unlike young spinal cord, serotonin alone did not produce any long-lasting synaptic enhancement in adult spinal dorsal horn neurons. However, co-application of the adenylyl cyclase activator forskolin and serotonin (5-HT) produced long-lasting enhancement, including the recruitment of functional AMPA receptor-mediated responses. Calcium-sensitive, calmodulin-regulated adenylyl cyclases (AC1, AC8) are required for the enhancement. Furthermore the thresholds for generating action potential responses were decreased, and, in many cases, co-application of forskolin and 5-HT led to the generation of action potentials by previously subthreshold stimulation of primary afferent fibers in the presence of the NMDA receptor blocker 2-amino-5-phosphonovaleric acid. Our results suggest that pure NMDA synapses exist on sensory neurons in adult spinal cord and that they may contribute to functional sensory transmission. The synergistic recruitment of functional AMPA responses by 5-HT and forskolin provides a new cellular mechanism for glutamatergic synapses in mammalian spinal cord.

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