Imaging of opioid receptors in the central nervous system

Abstract

In vivo functional imaging by means of positron emission tomography (PET) is the sole method for providing a quantitative measurement of μ-, κ and δ-opioid receptor-mediated signalling in the central nervous system. During the last two decades, measurements of changes to the regional brain opioidergic neuronal activation—mediated by endogenously produced opioid peptides, or exogenously administered opioid drugs—have been conducted in numerous chronic pain conditions, in epilepsy, as well as by stimulant- and opioidergic drugs. Although several PET-tracers have been used clinically for depiction and quantification of the opioid receptors changes, the underlying mechanisms for regulation of changes to the availability of opioid receptors are still unclear. After a presentation of the general signalling mechanisms of the opioid receptor system relevant for PET, a critical survey of the pharmacological properties of some currently available PET-tracers is presented. Clinical studies performed with different PET ligands are also reviewed and the compound-dependent findings are summarized. An outlook is given concluding with the tailoring of tracer properties, in order to facilitate for a selective addressment of dynamic changes to the availability of a single subclass, in combination with an optimization of the quantification framework are essentials for further progress in the field of in vivo opioid receptor imaging.

Human Experimental Pain Models for Assessing the Therapeutic Efficacy of Analgesic Drugs

“…For example, in vivo functional imaging by means of PET is a method for providing a quantitative measurement of opioid receptor-mediated signaling in the central nervous system. A decrease in opioid receptor availability related to acute pain has been demonstrated (Henriksen and Willoch, 2008). PET and SPECT have been used for imaging of the opioid system and and allow precise pharmacokinetic and pharmacodynamic measurements (Lever, 2007).…”

“…Moreover, the subjects receive radiation, and the expense for the synthesis and the PET ligand is high. Finally, the experimental setup and the choice of tracer may affect the results and explain any divergence in findings (Henriksen and Willoch, 2008).…”

Agonist and Antagonist Effects of ATP-Dependent Potassium Channel on Penicillin Induced Epilepsy in Rats

“…penisilin (500 IU,2,5 μl) uygulanmasıyla oluşturuldu. Penisilin uygulamasının 30. dakikasında tüm maddeler (salin, DMSO, pinasidil ve glibenklamid) intraperitoneal 15 (i.p.)…”

Neuropeptide Receptors in Pain Circuitries: Useful Targets for CNS Imaging with Non-Peptide Ligands Suitable for PET?

“…A role of neuropeptide receptors in pain perception and relief has been discovered already very early, even if, like in the case of opioids as an extensively investigated transducer of analgesic signals, it was initially not known that the endogenous transmitters of these receptors were peptides and it took centuries until it became possible to identify and to characterize human neuropeptide receptors [16]- [18].…”