Opioid Therapies and Cytochrome P450 Interactions Jeffrey Gudin, MD  Journal of Pain and Symptom Management  Volume 44, Issue 6, Pages S4-S14 (December 2012) DOI: 10.1016/j.jpainsymman.2012.08.013 Copyright © 2012 U.S. Cancer Pain Relief Committee Terms and Conditions

Fig. 1 The sites of action of broad-spectrum analgesics. Targeting multiple distinct components in the pain-signaling pathway—transduction, transmission, perception, and modulation—is increasingly viewed as offering additive, perhaps even supra-additive (synergistic) pain reduction. Coadministration of the α2-receptor agonist clonidine along with an opioid, for example, may yield significantly greater analgesic effects when compared with either agent alone. Although the neural pathways that govern pain are yet to be fully elucidated, a balanced analgesic approach using multiple agents with unique modes of action is thought to reduce the peripheral and central sensitization and inflammation that often characterize chronic pain disorders. Adapted from Kelly et al.8 Journal of Pain and Symptom Management 2012 44, S4-S14DOI: (10.1016/j.jpainsymman.2012.08.013) Copyright © 2012 U.S. Cancer Pain Relief Committee Terms and Conditions