Signal transduction in neuropathic pain, with special emphasis on the analgesic role of opioids - Part II: Moving basic science towards a new pharmacotherapy*

Abstract

Introduction In Part II of this trilogy, I investigate the extent to which current basic science can be applied to the development of novel entities with the potential for entering preclinical evaluation. Following on from the treatment in Part I, I explore in greater depth the role of cholecystokinin (CCK) as an anti-opioid peptide. A re-evaluation of earlier preclinical studies confirms an important role for selective antagonists of the CCKB receptor subtype as co-analgesics with morphine in patients with intractable pain.1–3 In attempting to unravel mechanisms whereby CCK antagonizes opioid signalling, I adhere to the theme developed in Part I. That is, cross-talk between CCK and opioid signalling may in some way reflect a conflict between the need of an injured neuronal cell to enter programmed survival or apoptosis and that of the clinician to produce relief of pain. Within the context of CCK-mediated anti-opioid signalling, a role is proposed for the protein tyrosine kinase (PTK), PYK2, which was recently cloned from human brain. The possibility that phospholipase A2 (PLA2) is an anti-opioid messenger of CCK is exciting because, as I discuss in *Part I of this trilogy was published in Pain Reviews 1999; 6(1); 3–33.