Opioid receptor imaging in man

Abstract

The existence of opioid receptors (OR) had long been suspected, but their demonstration in nervous tissue and the discovery of their natural ligands did not come until the 1970’s. By 1985, the study of brain OR was possible in vivo using Positron Emission Tomography (PET), thanks to technical advances in imaging and radiochemistry. Since then, multiple PET studies contributed to clarify the physiology and pathology of human endogenous opioid system in several conditions and pathologies. Thus, activation studies in tonic experimental pain have demonstrated opioid system activation in multiple opioid receptor bearing sites such as the amygdala, the ventrolateral thalamus, the insular cortex and hypothalamus, the anterior cingulate gyrus and the prefrontal cortex. Such activation is negatively correlated with the intensity of pain perception. Activation studies have also demonstrated sex-dependent and COMT (cathecol-O-methyltransferase)-dependent differences in the magnitude and direction of the activation of endogenous opioid systems. Endogenous opioid secretion is very likely to occur as a reaction to acute or chronic nociceptive pain, and PET studies have demonstrated a decrease in the binding of the exogenous ligand in patients suffering pain secondary to chronic inflammatory conditions like rheumatoid arthritis. In neuropathic pain (NP), endogenous reactive opioid secretion is also very likely as a global reaction to pain, but there are differences between central and peripheral causes of NP. Loss or inactivation of OR in the hemisphere containing the causal lesion (contralateral to clinical pain) has been demonstrated in central post-stroke pain, while no such lateralised loss seems to exists in peripheral NP. Difference in OR distribution abnormalities between peripheral and central types of NP might explain in part their differential response to exogenous opioids, which is better in peripheral NP. Motor Cortex Stimulation (MCS) for pain relief appears to induce endogenous opioid secretion in key areas of the endogenous opioid system, thus putatively explaining part of the mechanisms of action of this procedure. All these studies incite to the development of future investigations in order to clarify the role of the opioid system in various disorders of the nervous system, and, in chronic pain syndromes, to study the predictive potential of OR distribution abnormalities in the development of NP and in the clinical response of NP to aggressive therapeutic alternatives, like MCS.