Detectable levels of both neurotrophins (NTs) (left) and NTRs (right) can be found in healthy intervertebral discs (IVDs) (top). Nerve growth factor (NGF) has been detected in the outer layers of the annulus fibrosus (AF) as well as in nerve fibers reaching it; a similar pattern of distribution in the AF has also been reported for TrkA. Cultured nucleus pulposus (NP) cells also express NGF and TrkA. The more external layers of the AF express brain-derived neurotrophic factor (BDNF) and TrkB, and BDNF is also present in NP cells. p75NTR was present in the superficial layers of the AF as well as in the nerve fibers supplying the IVD. Degeneration of the IVD (bottom) occurs in parallel with increased levels of expression of NTs and NTRs. NGF and TrkA are overexpressed and detected in the AF; expression of BDNF and TrkB is also increased in both the AF and NP. Micrographs are examples of the immunohistochemical detection of NGF, BDNF, TrkA and TrkB in cells from herniated (not degenerated) human IVDs. Positive immunostaining was also found for NT-3 (data not shown), whereas results of immunolabeling for TrkC and p75NTR were always negative. FL, full-length; nf, nerve fibres; NgR, Nogo receptor.