Spinal expression of mRNA for immediate early genes in a model of chronic pain

We have used a partial nerve ligation model of chronic pain to investigate if there are changes in the expression of mRNA for several immediate early genes (IEG) that correlate in time with the initial adaptive behavioural changes and with development of allodynia in this model. The animals were inspected for typical changes in posture, and mechanical allodynia was evaluated using von Frey filaments. Expression of three of the immediate early genes examined, c-fos, NGFI-A and jun B, was transiently increased in the ipsilateral dorsal horn of the spinal cord following the partial ligation of the sciatic nerve. The time course and extent of these changes were similar to those reported for acute noxious stimuli. c-jun mRNA expression was significantly enhanced, after a delay of more than 12 h, and then remained elevated over the entire studied period of 4 weeks. These changes occurred only in the ventral horn, particularly in lamina IX. Except for c-jun mRNA, all changes were transient despite behavioural evidence for continuing allodynia. These results from the partial nerve ligation model, when compared with results obtained using other models of acute or chronic nerve injury, suggest that the immediate early genes we have examined are not sufficient to explain the transition to chronic pain states. The results also show that in this model of chronic pain there are prolonged adaptive changes in motor neurons and that these changes are temporally associated with the development of chronic pain and allodynia.