Dorsal root ganglion neurons respond with prolonged extracellular signal-regulated protein kinase phosphorylation following noxious heat and cold stimulation.

In the present study the time course of extracellular signal-regulated protein kinase phosphorylation (pERK1/2 appearance) in lumbar sensory dorsal root ganglia (DRG) was determined following a 5-min noxious heat or a noxious cold stimulus to the hind paw of the rat. The thermal stimuli were chosen to activate transient receptor potential (TRP) channels, but not to induce tissue damage. A quantitative analysis of phospho-ERK1/2 was performed by protein extraction and Western blot analysis. Western blot analysis showed that following the heat stimulus, phosphorylation of ERK1/2 increased 2-3-fold between 10 and 30min in the DRG on the ipsilateral side. High levels were maintained from 30min up to 16h. Following the cold stimulus to the paw, pERK1/2 immediately increased 2-fold within 2min in the DRG on the ipsilateral side, it declined within 2h and reached a second peak at 4h. In the DRGs on the contralateral side of the paw's heat or cold immersion the pERK1/2 remained low at all time points investigated. Fluorescence immunohistochemistry of the DRG following the thermal stimuli revealed an increased cytoplasmic staining for pERK1/2 in neurons. The present results show that following a 5-min nociceptive thermal stimulus sensory neurons respond with a characteristic long-lasting phosphorylation of ERK1/2.