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Toward a central origin of nociceptive hypersensitivity in adult rats after a neonatal maternal separation
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  • Clémence Gieré,
  • Yannick Menger,
  • Hannah Illouz,
  • Vincent Lelièvre,
  • Meggane Melchior,
  • Pierrick Poisbeau
Clémence Gieré
Centre national de la Recherche Scientifique, Université de Strasbourg
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Yannick Menger
Centre national de la Recherche Scientifique, Université de Strasbourg
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Hannah Illouz
Centre national de la Recherche Scientifique, Université de Strasbourg
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Vincent Lelièvre
Centre national de la Recherche Scientifique, Université de Strasbourg
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Meggane Melchior
Université de Strasbourg, Centre national de la recherche Scientifique
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Pierrick Poisbeau
Centre national de la Recherche Scientifique, Université de Strasbourg

Corresponding Author:[email protected]

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Abstract

Early life adversities alter the development of a still maturing nervous system and can have long-term consequences on its function at adult age. This include nociceptive circuits that are critical to shape an adaptive pain response to protect our organism from potentially damaging insults. As such, adult rats with a history of neonatal maternal separation (NMS) display a visceral and somatic nociceptive hypersensitivity and inefficient analgesic responses to stress. In this study, we have characterized the consequences of NMS on wide dynamic range neurons (WDR) in the spinal cord of anesthetized adult rat during the nociceptive processing of hot and cold noxious information. We found that WDR neurons of NMS rats display an excessive coding of mechanical and thermal information applied at the rat hindpaws. This nicely explains the hypernociceptive behaviors seen after noxious mechanical, cold and hot peripheral stimulation. A peripheral change in the expression of molecular transducers for these stimuli (i.e. TRPV1, TRPM8, TRPA1) does not seem to account for this general hyperexcitability. Instead, a decreased chloride-mediated inhibitory tone on WDR neurons may play a role as indicated by the abnormal elevated of the type 1 Na-K-Cl cotransporter transcripts. Altogether, we propose that long-term consequences of NMS is associated with a reduced spinal cord inhibition favoring the expression of pain hypersensitivity. We cannot exclude that this phenomenon is also present at supraspinal sites as other NMS-associated symptoms include also excessive anxiety and impaired sociability.
06 Jul 2023Submitted to European Journal of Neuroscience
07 Jul 2023Submission Checks Completed
07 Jul 2023Assigned to Editor
07 Jul 2023Review(s) Completed, Editorial Evaluation Pending
10 Jul 2023Reviewer(s) Assigned
23 Aug 2023Editorial Decision: Revise Minor
28 Sep 20231st Revision Received
28 Sep 2023Submission Checks Completed
28 Sep 2023Assigned to Editor
28 Sep 2023Review(s) Completed, Editorial Evaluation Pending
02 Oct 2023Editorial Decision: Accept