Multiple Opioid Systems and Chronic Pain

Central opioid analgesics such as morphine are universally employed in the alleviation of severe and, in particular, chronic pain. In view of their key importance, there is continuing interest in the mechanisms underlying their analgesic actions and in the functional response of endogenous opioid systems to chronic pain. It is with the latter of these themes that the present review is concerned. The multiplicity of endogenous opioid systems is addressed in detail in other chapters in this volume and summarized in Table 1. The relationship between multiple opioid peptides, on the one hand, and multiple opioid receptors, on the other, is still unclear. Nevertheless, it seems that dynorphin A1 – I7 (DYN) and other products encoded by the gene for pro-dynorphin (PDYN), such as DYN A1 – 8 DYN B, and α neo- endorphin, act via κ-receptors. Pro-enkephalin (PENK)-derived opioids such as met-enkephalin (ME) and ME-Arg-Gly-Leu (MERGL) possibly exert their actions via δ-receptors, though this is still not certain. β-Endorphin (β-EP) can act via μ- and δ-receptors and has, in addition, been proposed to interact with a so-called e-receptor. (As there is no relevant information concerning this site and chronic pain, it is not further discussed herein.) μ-,δ- and κ-receptors can each mediate antinociception at cerebral and spinal sites and may interact in the expression of their antinociceptive effects (BESSE et al. 1990; JIANG et al. 1990; MIASKOWSKI et al. 1990a; SUTIERS et al. 1990; see HEYMAN et al. 1988; MILLAN 1986, 1990; see also Chaps. 32 and 33).