BDNF and GDNF expression in discrete populations of nociceptors

The brain derived neurotrophic factor (BDNF) and the glial cell line-derived neurotrophic factor (GDNF) are growth factors that promote the survival and differentiation of sensory neurons and intervene in the control of nociceptive neurotransmission. Both are synthesized by dorsal root ganglion (DRG) neurons and are anterogradely transported to the central terminals of the spinal cord dorsal horn. To better investigate the specific expression pattern of BDNF and GDNF in nociceptors, we studied their localization in relationship to other established nociceptive markers in the mouse DRGs. Our results can be summarized as follows: (1) BDNF and GDNF are expressed in distinct populations of small-to medium-sized DRG neurons, with BDNF three times more frequently expressed than GDNF (186.4 ± 1.7 BDNF-immunoreactive (IR) cells/DRG vs 57.7 ± 0.3 GDNF-IR cells/DRG; n = 3 mice); (2) A subset of BDNF-expressing neurons and a subset of GDNF-expressing neurons are of the peptidergic type; (3) BDNF-IR neurons are a subpopulation of calcitonin gene-related peptide (CGRP)-IR neurons (41.3 ± 0.4%), also positive for substance P (SP) (42.3 ± 0.1%), but not for somatostatin (SST); (4) GDNF-IR neurons are a subpopulation of CGRP-IR neurons (95.8 ± 0.1%), also positive for SST (67.9 ± 2.1%), but not SP; (5) Neither BDNF nor GDNF colocalized with the non-peptidergic marker IB4. Our results show the existence of two subpopulations of peptidergic nociceptors characterized by the presence of CGRP, one expressing BDNF (plus SP), the other expressing GDNF (plus SST), suggesting a different role for these two neurotrophic factors in the discrimination of specific painful stimuli modalities.