Abstract
Clinical and basic science research have revealed persistent effects of early-life injury on nociceptive processing and resulting pain sensitivity. While recent work has identified clear deficits in fast GABA(A)- and glycine receptor-mediated inhibition in the adult spinal dorsal horn after neonatal tissue damage, the effects of early injury on slow, metabotropic inhibition within spinal pain circuits are poorly understood. Here we provide evidence that neonatal surgical incision significantly enhances postsynaptic GABA(B) receptor signaling within the mature superficial dorsal horn (SDH) in a cell type-dependent manner. In vitro patch-clamp recordings were obtained from identified lamina I projection neurons and GABAergic interneurons in the SDH of adult female mice following hindpaw incision at postnatal day (P)3. Early tissue damage increased the density of the outward current evoked by baclofen, a selective GABA(B) receptor agonist, in projection neurons but not inhibitory interneurons. This could reflect enhanced postsynaptic expression of downstream G protein-coupled inward-rectifying potassium channels (GIRKs), as the response to the GIRK agonist ML297 was greater in projection neurons from neonatally incised mice compared to naive littermate controls. Meanwhile, presynaptic GABA(B) receptor-mediated reduction of spontaneous neurotransmitter release onto both neuronal populations was unaffected by early-life injury. Collectively, our findings suggest that ascending nociceptive transmission to the adult brain is under stronger control by spinal metabotropic inhibition in the aftermath of neonatal tissue damage.