Peripheral nerve injury potentiates excitatory synaptic transmission in locus coeruleus neurons.

Peripheral nerve injury (PNI) is believed to cause maladaptive changes at synaptic level, leading to neuropathic pain which is difficult to treat with common analgesic drugs. Noradrenergic locus coeruleus (LC) neurons have a crucial role in neuropathic pain modulation. In this study we examined whether chronic constriction injury (CCI) could affect glutamatergic synaptic transmission in LC neurons. CCI was performed on P10 to P12 Sprague Dawley pups. Seven days after CCI, horizontal slices of brainstem (300μm thick) were prepared and whole-cell patch clamp recording was performed. Evoked and spontaneous excitatory postsynaptic currents (eEPSC and sEPSC) were recorded from LC neurons at a holding potential of -70mV, in the presence of bicuculline (20μM). The sEPSCs recorded from LC neurons of neuropathic rats showed a significant increase in amplitude, but not in frequency. The eEPSC amplitude in neurons of rats under gone CCI was significantly increased compared to the control group (P<0.05). The paired pulse ratio (PPR) elicited with different inter-stimulus intervals (50-250ms) did not show any difference between neurons of CCI and control pups. This study shows that PNI increases excitatory synaptic transmission in LC neurons 7days after chronic constriction injury. The observed synaptic potentiation is mainly due to postsynaptic mechanisms.