title: A novel population of cholinergic neurons in the macaque spinal dorsal horn of potential clinical relevance for pain therapy.
abstract: Endogenous acetylcholine (ACh) is a well-known modulator of nociceptive transmission in the spinal cord of rodents. It arises mainly from a sparse population of cholinergic interneurons located in the dorsal horn of the spinal cord. This population was thought to be absent from the spinal cord of monkey, what might suggest that spinal ACh would not be a relevant clinical target for pain therapy. In humans, however, pain responses can be modulated by spinal ACh, as evidenced by the increasingly used analgesic procedure (for postoperative and labor patients) consisting of the epidural injection of the acetylcholinesterase inhibitor neostigmine. The source and target of this ACh remain yet to be elucidated. In this study, we used an immunolabeling for choline acetyltransferase to demonstrate, for the first time, the presence of a plexus of cholinergic fibers in laminae II-III of the dorsal horn of the macaque monkey. Moreover, we show the presence of numerous cholinergic cell bodies within the same laminae and compared their density and morphological properties with those previously described in rodents. An electron microscopy analysis demonstrates that cholinergic boutons are presynaptic to dorsal horn neurons as well as to the terminals of sensory primary afferents, suggesting that they are likely to modulate incoming somatosensory information. Our data suggest that this newly identified dorsal horn cholinergic system in monkeys is the source of the ACh involved in the analgesic effects of epidural neostigmine and could be more specifically targeted for novel therapeutic strategies for pain management in humans.
authors: Institut des Neurosciences Cellulaires et Intégratives, Unité Propre de Recherche 3212, Centre National de la Recherche Scientifique, Department Nociception et Douleur, Strasbourg Cedex 67084, France.
authors: Sophie Anne
authors: SA
authors: Pawlowski
authors: Stéphane
authors: S
authors: Gaillard
authors: Imad
authors: I
authors: Ghorayeb
authors: Alfredo
authors: A
authors: Ribeiro-da-Silva
authors: Rémy
authors: R
authors: Schlichter
authors: Matilde
authors: M
authors: Cordero-Erausquin
mesh_terms: D000818:Animals; D002452:Cell Count; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D059329:Cholinergic Neurons / Q000502:physiology* / Q000648:ultrastructure; D005260:Female; D021621:Imaging, Three-Dimensional; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D016253:Microscopy, Immunoelectron; D009419:Nerve Tissue Proteins / Q000378:metabolism; D020671:Posterior Horn Cells / Q000502:physiology* / Q000648:ultrastructure; D011493:Protein Kinase C / Q000378:metabolism; D013045:Species Specificity; D013116:Spinal Cord / Q000166:cytology* / Q000648:ultrastructure; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure; D050494:Vesicular Acetylcholine Transport Proteins / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; C493460:Slc18a3 protein, mouse; D050494:Vesicular Acetylcholine Transport Proteins; D005680:gamma-Aminobutyric Acid; D002795:Choline O-Acetyltransferase; D011493:Protein Kinase C