title: Aberrant synaptic integration in adult lamina I projection neurons following neonatal tissue damage.
abstract: Mounting evidence suggests that neonatal tissue damage evokes alterations in spinal pain reflexes which persist into adulthood. However, less is known about potential concomitant effects on the transmission of nociceptive information to the brain, as the degree to which early injury modulates synaptic integration and membrane excitability in mature spinal projection neurons remains unclear. Here we demonstrate that neonatal surgical injury leads to a significant shift in the balance between synaptic excitation and inhibition onto identified lamina I projection neurons of the adult mouse spinal cord. The strength of direct primary afferent input to mature spino-parabrachial neurons was enhanced following neonatal tissue damage, whereas the efficacy of both GABAergic and glycinergic inhibition onto the same population was compromised. This was accompanied by reorganization in the pattern of sensory input to adult projection neurons, which included a greater prevalence of monosynaptic input from low-threshold A-fibers when preceded by early tissue damage. In addition, neonatal incision resulted in greater primary afferent-evoked action potential discharge in mature projection neurons. Overall, these results demonstrate that tissue damage during early life causes a long-term increase in the gain of spinal nociceptive circuits, and suggest that the prolonged consequences of neonatal trauma may not be restricted to the spinal cord but rather include excessive ascending signaling to supraspinal pain centers.
authors: Pain Research Center, Department of Anesthesiology, University of Cincinnati Medical Center, Cincinnati, Ohio 45267.
authors: Jie
authors: J
authors: Li
authors: Pain Research Center, Department of Anesthesiology, University of Cincinnati Medical Center, Cincinnati, Ohio 45267.
authors: Elizabeth
authors: http://orcid.org/0000-0002-7592-4617
authors: E
authors: Kritzer
authors: Pain Research Center, Department of Anesthesiology, University of Cincinnati Medical Center, Cincinnati, Ohio 45267.
authors: Paige E
authors: PE
authors: Craig
authors: Pain Research Center, Department of Anesthesiology, University of Cincinnati Medical Center, Cincinnati, Ohio 45267 mark.baccei@uc.edu.
authors: Mark L
authors: ML
authors: Baccei
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D005260:Female; D050487:Glycine Plasma Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D009415:Nerve Net / Q000473:pathology*; D009474:Neurons / Q000473:pathology*; D009475:Neurons, Afferent / Q000473:pathology; D009619:Nociceptors; D010146:Pain / Q000473:pathology*; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000473:pathology; D011247:Pregnancy; D013116:Spinal Cord / Q000473:pathology*; D013569:Synapses / Q000473:pathology*; D009435:Synaptic Transmission; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000378:metabolism
chemical_list: D050487:Glycine Plasma Membrane Transport Proteins; C493270:Slc6a5 protein, mouse; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C492244:Viaat protein, mouse
keywords: action potential; dorsal horn; injury; patch-clamp; spinal cord; synapse