Effect of peripheral axotomy on pain-related behavior and dorsal root ganglion neurons excitability in NPY transgenic rats

In order to clarify the physiologic role of NPY in sensory processing, we obtained intracellular recordings of DRG neurons from wild type (WT) and NPY overexpressing transgenic rats (NPY-TG) before and after injury. We investigated medium and large diameter DRG neurons since upregulation of NPY peptide following the nerve injury occurs primarily in those cells. Neurons were classified as Aalpha/beta and Adelta using conduction velocity and action potential duration. Prior to the injury, Aalpha/beta neurons of NPY-TG rats conducted more slowly and had a more brief AHP than similar cells from the WT group. Adelta neurons at baseline conducted faster in TG animals compared to WT. Ligation of the 5th lumbar spinal nerve (SNL) produced certain changes in Aalpha/beta cells that were evident only in the TG group. These include increased refractory period, increased input resistance, AHP prolongation and a depolarizing shift in threshold for AP initiation. The expected injury-induced CV slowing was not seen in NPY-TG Aalpha/beta cells. In the Adelta cell group, injury produced a depolarizing shift in the resting membrane potential, an increase in AP duration and decrease in AHP and refractory period duration only in WT rats, while NPY-TG cells lacked these injury-induced changes. Behavior tests showed diminished sensory response to nerve injury in NPY-TG rats, i.e., shorter duration of enhanced pain-related behavior and attenuation of contralateral effect. In conclusion, our observations suggest that NPY overexpression leads to reduced neuronal activity following nerve injury in a cell-specific manner.