We have attempted to define some of the patterns of expression of the IEG Fos in pain-related states. On one level, Fos may be used simply as marker of afferent stimulation and disease state, and in this respect Fos activation may be a useful tool after nociceptive stimulation to examine the effectiveness of different analgesic regimens. For example, certain analgesics such as opioids, alpha 2 agonists and local anaesthetics are more effective when given pre-emptively or early in the injury rather than later on. Furthermore, the persistent expression of Fos in the presence of high dose pre-emptive opioids is disturbing and yet it may explain variable success of studies attempting to show pre-emptive analgesia with opioid-based analgesic regimens. We suggest that Fos expression, as well as defining the magnitude and the duration of insult to the spinal cord seems also to signal the adaptive responses of the nervous system to nociceptive insult. Though we have focused on only one IEG, c-fos, and attempted to relate appearance to known functional changes within the spinal cord, there are in fact many more genes known to be upregulated with the same or slower kinetics (e.g. Fos B, FRA-1, FRA-2, Jun B, Jun D, NGFI-A). Increased understanding of the role of these genes is likely to lead to many novel targets in the search for normalization or restoration of spinal cord function in pain states and after nerve injury.