Life sciences
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Extracellular signal-regulated protein kinase (ERK) is a mitogen-activated protein kinase (MAPK) that mediates intracellular signal transduction in response to a variety of stimuli. ERK is involved in cell proliferation and differentiation and in neuronal plasticity, including long-term potentiation, learning, and memory. Here, we present recently accumulating data about the roles of MAPK pathways in mediating the neuronal plasticity that contributes to pain hypersensitivity. ⋯ On the other hand, peripheral inflammation and axotomy also induces p38 MAPK activation in DRG neurons. Taken together, these findings indicate that activation of MAPK in nociceptive neurons may participate in generating pain hypersensitivity through transcription-dependent and -independent means. Thus, inhibition of MAPK signaling in the primary afferents, as well as in the spinal cord, may provide a fruitful strategy for the development of novel analgesics.
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Previously, it was believed that the lumbar intervertebral disc was innervated segmentally by dorsal root ganglion (DRG) neurons via the sinuvertebral nerves. Recently, it was demonstrated using retrograde tracing methods that the lower disc (L5-L6) is innervated predominantly by upper (L1 and L2) DRG neurons via the sympathetic trunks. Furthermore, we investigated the expression of various pain-related molecules such as calcitonin gene-related peptide (CGRP), isolectin B4 (IB4), P2X(3) receptor and vanniloid receptor 1 (VR1) in DRG neurons innervating the disc using a combination of immunostaining with the retrograde tracing method. ⋯ In addition, we also demonstrated P2X(3)- and VR1-immunoreactivity in DRG neurons innervating the disc and noted that they were mainly localized in NGF-dependent neurons. It is well known that NGF has sensitizing effects on DRG neurons, with a recent study demonstratng the presence of NGF in the painful intervertebral disc. Therefore, it is suggested that NGF is involved in the generation of discogenic low back pain.