Modulation of developing dorsal horn synapses by tissue injury

Although tissue injury can evoke significant hyperalgesia in infants from the first days of life, little is known about how injury affects emergent central pain networks at the synaptic level. Recent studies have investigated whether tissue damage at different ages has distinct consequences for synaptic function in the rat superficial dorsal horn (SDH) using in vitro patch clamp recordings from spinal cord slices prepared at different times after an injury. The results demonstrate that tissue damage during the first postnatal week transiently increases the frequency (but not amplitude) of miniature excitatory postsynaptic currents (mEPSCs), while no changes are observed at inhibitory synapses onto the same neurons. Prolonged blockade of sciatic nerve activity in vivo with bupivacaine hydroxide or tetrodotoxin prevented the elevation in mEPSC frequency following early injury. In contrast, tissue damage during the third postnatal week failed to significantly alter spontaneous excitatory or inhibitory synaptic transmission in the SDH. These data show that afferent activity arising from injured peripheral tissue selectively regulates glutamatergic synaptic signaling in the developing SDH in a highly age-dependent manner.