Peripheral and central alterations affecting spinal nociceptive processing and pain at adulthood in rats exposed to neonatal maternal deprivation.
The nociceptive system of rodents is not fully developed and functional at birth. Specifically, C fibers transmitting peripheral nociceptive information establish synaptic connections in the spinal cord already during the embryonic period that only become fully functional after birth. Here, we studied the consequences of neonatal maternal deprivation (NMD, 3 h/day, P2-P12) on the functional establishment of C fiber-mediated neurotransmission in spinal cord and of pain-related behavior. In vivo recording revealed that C fiber-mediated excitation of spinal cord neurons could be observed at P14 only in control but not in NMD rats. NMD was associated with a strong alteration in the expression of growth factors controlling C nociceptor maturation as well as two-pore domain K+ channels known to set nociceptive thresholds. In good agreement, C-type sensory neurons from NMD animals appeared to be hypoexcitable but functionally connected to spinal neurons, especially those expressing TRPV1 receptors. In vivo and in vitro recordings of lamina II spinal neurons at P14 revealed that the NMD-related lack of C fiber-evoked responses resulted from an inhibitory barrage in the spinal cord dorsal horn. Eventually, C-type sensory-spinal processing could be recovered after a delay of about 10 days in NMD animals. However, animals remained hypersensitive to noxious stimulus up to P100 and this might be due to an excessive expression of Nav1.8 transcripts in DRG neurons. Together, our data provide evidence for a deleterious impact of perinatal stress exposure on the maturation of the sensory-spinal nociceptive system that may contribute to the nociceptive hypersensitivity in early adulthood.
Institute of Cellular and Integrative Neurosciences (INCI), Centre National de la Recherche Scientifique, University of Strasbourg, 5 Rue Blaise Pascal, F-67084, Strasbourg, France.
Pierre-Eric
PE
Juif
Department of Veterinary Sciences, Università degli Studi di Torino, Torino, Italy.
Chiara
C
Salio
Institute of Cellular and Integrative Neurosciences (INCI), Centre National de la Recherche Scientifique, University of Strasbourg, 5 Rue Blaise Pascal, F-67084, Strasbourg, France.
Vivien
V
Zell
Institute of Cellular and Integrative Neurosciences (INCI), Centre National de la Recherche Scientifique, University of Strasbourg, 5 Rue Blaise Pascal, F-67084, Strasbourg, France.
Meggane
M
Melchior
Institute of Cellular and Integrative Neurosciences (INCI), Centre National de la Recherche Scientifique, University of Strasbourg, 5 Rue Blaise Pascal, F-67084, Strasbourg, France.
Adrien
A
Lacaud
Institute of Cellular and Integrative Neurosciences (INCI), Centre National de la Recherche Scientifique, University of Strasbourg, 5 Rue Blaise Pascal, F-67084, Strasbourg, France.
Nathalie
N
Petit-Demouliere
Department of Veterinary Sciences, Università degli Studi di Torino, Torino, Italy.
Francesco
F
Ferrini
Institute of Cellular and Integrative Neurosciences (INCI), Centre National de la Recherche Scientifique, University of Strasbourg, 5 Rue Blaise Pascal, F-67084, Strasbourg, France.
Pascal
P
Darbon
Laboratory of Neurophysiology and Psychobiology, University of Luxembourg, Luxembourg, Luxembourg.
Ulrike
U
Hanesch
Laboratory of Neurophysiology and Psychobiology, University of Luxembourg, Luxembourg, Luxembourg.
Fernand
F
Anton
Department of Veterinary Sciences, Università degli Studi di Torino, Torino, Italy.
Adalberto
A
Merighi
Institute of Cellular and Integrative Neurosciences (INCI), Centre National de la Recherche Scientifique, University of Strasbourg, 5 Rue Blaise Pascal, F-67084, Strasbourg, France.
Vincent
V
Lelièvre
Institute of Cellular and Integrative Neurosciences (INCI), Centre National de la Recherche Scientifique, University of Strasbourg, 5 Rue Blaise Pascal, F-67084, Strasbourg, France.
Pierrick
P
Poisbeau
D000818:Animals; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008426:Maternal Deprivation; D062559:NAV1.8 Voltage-Gated Sodium Channel / Q000235:genetics / Q000378:metabolism; D059225:Nociception; D059226:Nociceptive Pain / Q000503:physiopathology*; D009619:Nociceptors / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism / Q000502:physiology*; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism
D062559:NAV1.8 Voltage-Gated Sodium Channel; D015221:Potassium Channels; C568319:Scn10a protein, rat; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat
C fiber; GABAergic inhibition; neonatal maternal deprivation; spinal nociceptive processing; wide dynamic range neurons