Besides supraspinal (see Heinricher and Morgan, Chap. 3 this vol.) and peripheral sites (see Stein, Cabot, and Schäfer, Chap. 5 this vol.), the dorsal horn (DH) of the spinal cord is a major area in which opioids exert their analgesic action. Thus, opioids administered at the spinal level produce a powerful analgesia in animals and humans (see Yaksh, 1997). Furthermore, whatever its route of administration, the most often used analgesic agent, morphine, exerts part of its antinociceptive effects by acting at spinal opioid receptors (Le Bars et al., 1976).
Opioid receptors of the μ, δ, and κ types have been cloned (see Gavériaux-Ruff and Kieffer, Chap. 1, this vol.). The existence of subclasses of these receptors: μ1, and μ2, δ1, and δ2, κ1, κ2, and κ3, has been postulated on the basis of pharmacologic data, but molecular biology investigations have not yet provided support for this hypothesis (see Dhawan et al., 1996). Possible variations in the post-translational processing of the receptor proteins might account for this pharmacologic heterogeneity, which has led to the distinction of receptor subtypes, notably in the spinal cord. Endogenous ligands for opioid receptors (see Roques, Noble, and Fournié-Zaluski Chap. 2 this vol.) are also present at the spinal level. In particular, endogenous opioid systems are strategically located in the DH, where primary afferent fibers (PAF), whose cell bodies are located in dorsal root ganglia (DRG), convey nociceptive messages from the periphery.