Mitogen-activated protein kinases (MAPKs) are able to transduce extracellular stimuli into intracellular posttranslational and transcriptional responses in dorsal root ganglion (DRG). We have examined the phosphorylation of MAPKs, such as extracellular signal-regulated kinase (ERK) and p38, and found two kinds of responses of ERK and p38, in primary afferent neurons. One response involves rapid alteration of MAPKs, which noxious stimulation of the peripheral tissue induces in the DRG. We found that noxious stimulation of the peripheral tissue very rapidly induced phosphorylation of ERK and p38 in DRG neurons. Phosphorylation of MAPKs might be very useful as markers of primary afferent activation after noxious stimulation. Another response is the long-term changes in the DRG after a variety of types of neuropathic injury to the peripheral nerves. We found that chronic constriction injury (CCI) induced phosphorylation in ERK and p38 MAPK in different subpopulations of DRG neurons and also in satellite glial cells. L5 spinal nerve ligation (SNL) induced phosphorylation in p38 MAPK in neighboring L4 DRG neurons. We have also found that p38 inhibitors attenuated BDNF and TRPV1 expression increased in the L4 DRG and thermal hyperalgesia after L5 SNL. These data indicate that dynamic changes occur in uninjured primary afferent neurons, as well as injured neurons in neuropathic pain models, and might be important for the transmission of exaggerated pain (peripheral sensitization) in neuropathic pain conditions.

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