title: Excitatory synapses in the rat superficial dorsal horn are strengthened following peripheral inflammation during early postnatal development.
abstract: Peripheral inflammation can cause prolonged changes in pain sensitivity if it occurs during a critical period of early postnatal development, suggesting that neonatal pain circuits respond to tissue damage in a fundamentally different manner. However, the effects of early tissue injury on the function of emergent central pain networks have yet to be characterized at the synaptic level. Here, we investigated whether inflammation at different postnatal ages has distinct consequences for synaptic function in the superficial dorsal horn (SDH) of the rat spinal cord using in vitro patch-clamp techniques. Subcutaneous injections of carrageenan (CARR) into the hindpaw at postnatal day (P) 2 significantly increased the frequency, but not amplitude, of miniature excitatory postsynaptic currents (mEPSCs) in P3-4 SDH neurons compared to naïve controls, while no changes were observed at inhibitory synapses onto the same neurons. The paired-pulse ratio of evoked EPSCs was unaltered by CARR at P2, suggesting that the elevation in mEPSC frequency following inflammation does not reflect an enhanced probability of glutamate release within the SDH. The potentiation of glutamatergic synapses did not persist beyond the duration of the injury, as the observed difference in mEPSC frequency had resolved by P10-11. In contrast, peripheral inflammation at P9 or P17 failed to significantly alter excitatory or inhibitory synaptic efficacy in the SDH. Meanwhile, carrageenan decreased the inward rectification of AMPAR-mediated currents throughout the first three postnatal weeks. These data suggest that distinct synaptic mechanisms may underlie central sensitization in the immature and mature spinal cords under pathological conditions.
authors.affiliation: Pain Research Center, Department of Anesthesiology, University of Cincinnati Medical Center, 231 Albert Sabin Way, Cincinnati, OH 45267, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Mark L
authors.initials: ML
authors.lastname: Baccei
mesh_terms: D000200:Action Potentials; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D019706:Excitatory Postsynaptic Potentials; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology*; D007249:Inflammation / Q000150:complications / Q000503:physiopathology*; D020671:Posterior Horn Cells / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses; D009435:Synaptic Transmission; D014110:Touch