Fig. 3.

The cells of the intervertebral disc (IVD) can be both a source and a target for neurotrophins (NTs). According to the classic neurotrophic theory, NTs produced in the IVD, especially nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), can be retrogradely transported to the soma of sensory neurons (blue diamond) where they potentiate nerve growth and expression of specific neurotransmitters like substance P or calcitonin gene-related peptide, as well as other molecules related to nociception. Interestingly, the dorsal root ganglion (DRG) neurons innervating IVDs express receptors for these NTs. However, DRG neurons that innervate the IVD also produce NTs, which can be transported anterogradely to the IVD (especially NGF) and interact with NTRs expressed in the nucleus pulposus cells stimulating the production of several molecules. Furthermore, they can reach the dorsal horn of the spinal cord (especially BDNF; red diamond) to modulate synaptic transmission. Finally, expression of both NTs and NTRs in cells of the IVD strongly suggests autocrinia and/or paracrinia.