Opioidergic signaling mechanisms in pain and dependence: PET opioid receptor binding. I. animal studies.

We are all naturally dependent on opioids for our emotional health. The opioid system is activated during the experience of pain, and opioids are used as analgesia and for abuse. Intentionally, opioid analgesia in pain and opioid drug abuse are contrary t o each other, but there are several common features shared as they imply a continuous agonist-mediated stimulation over a longer period of time. When administered in a state of pain, the long-term administration of opioids may result in pain relief, funct ional improvement, and increased quality of life. However, the long-term use of opioids is known to result in tolerance and physical dependence. One consequence of repeated drug administration is the development of adaptations in the nervous system, somet imes termed 'drug-opposite' responses, such as µ-agonist-induced hyperalgesia. The project is divided in 5 WorkPackages (WP). WP1 focus on implementation and development of new methods. WP2 and WP3 are investigating the activation of the endogenous opio id system to a noxious stimulus and modulations in opioid receptor binding to exougenously administred opioids in rats. Alterations in binding is related receptor gene expression and novelty tests. WP4 and WP5 are clinical studies of pain and addiction. These parts of the project are taken out due to the limited financial frame. It will be applied for funding to involve the human PET-studies in future.