Somatosensory neurons respond heterogeneously to a conditioning lesion

Regeneration of peripheral neurons after a nerve crush is enhanced if the axons have received a prior injury, a phenomenon known as the conditioning lesion response (CLR). Neurons in the mouse L3-L5 dorsal root ganglia (DRGs) that project into the sciatic nerve are commonly used to examine the CLR. These ganglia contain a diverse population of somatosensory neurons, which exhibit dramatic heterogeneity in their response to a CL. As reported previously, the nociceptors [i.e., isolectin B4 binding (IB4+) and calcitonin gene-related peptide positive (CGRP+) neurons] do not show enhanced axonal growth in culture after an in vivo CL, whereas the remaining neurons on average do. We asked whether the failure to produce a CLR was an inherent property of certain neurons. Two difficulties in interpreting previous findings are that only about half of the neurons in these ganglia project into the sciatic nerve and that both IB4 binding and CGRP immunoreactivity decrease after axotomy. Therefore, a possibility not considered previously is that neurons that are still CGRP+ or IB4+ after sciatic nerve transection have not been axotomized. Genetic mutants that express a reporter in CGRP neurons such that its expression is unchanged after axotomy demonstrate that the absence of a CLR is an inherent property of these neurons; however, expression of a reporter in the MrgD (Mas-related gene D)/IB4 neurons demonstrate that these neurons in fact do exhibit a CLR. Among the CGRP-/IB4- neurons, two populations found to exhibit a CLR are tropomyosin receptor kinase C+ (TrkC+) and MrgD+ neurons.