Peripheral tissues opioid system

In addition to the weU-defined opioid systems in the central nervous system, the three opioid peptides and their precursor mRNA have also been identified in peripheral tissues. ( -Endorphin is most abundant in the pituitary, where it exists in corticotroph cells with ACTH in the anterior lobe and in melanotroph cells with MSH in the intermediate lobe (59). Enkephalin and pre-pro-enkephalin mRNA have been identified in the adrenal medulla (60) and this has been the source of material for many studies of pro-enkephalin synthesis and regulation. Pre-pro-enkephalin mRNA has also been identified in the anterior and posterior lobes of the pituitary (61). mRNA for all three opioid precursors has been identified in the reproductive system (62—64). POMC... 

The investigations of Stein (1991) and Stein et al. (1999) have shown that pain-relevant opioid receptors are not only situated in the central nervous system but also in peripheral organs and tissues. Investigations in pain models with peripherally-acting opioids indicate that k-... 

Subsequently, numerous peptides with opioid-like effects have been found in the central nervous system and in peripheral tissues. These endogenous opioid peptides vary in size, but their amino terminals mostly share a similar enkephalin sequence of amino acids. Currently, four separate, individually gene-derived families of endogenous opioid peptides are recognized the endorphins, the enkephalins, the dynorphins and the endomorphins [17a], -Endorphin interacts predominantly with n and 6 receptors, Leu-enkephalin and Met-enkephalin interact predominantly with 5 receptors, dynorphin shows preference for k receptors [17b], while endomorphins 1 and 2 exhibit... 

The mechanisms of pain and the ability to control pain may vary in different pain states. This is of particular importance in consideration of a rational basis for the treatment of both inflammatory and neuropathic pain where the damage to tissue and nerve leads to alterations in both the peripheral and central mechanisms of pain signalling. In respect of existing drug therapies, this plasticity, the ability of the system to change in the face of a particular pain syndrome, explains the effectiveness of NSAIDs in inflammatory conditions and yet is also responsible for some of the limitations in the effectiveness of opioids in neuropathic pain. 

These heterocyclic opioid agents, with a diverse structure, act by binding to one or more of the opioid receptor sites which are to be found on neural (and some other sites) in the central and peripheral nervous systems. It is now recognized that these are the natural receptor sites for recognition of the endogenous members of the peptide opioid neurotransmitters families, which are found in neuronal tissue of the brain and elsewhere. 

---