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The density of opioid receptors is labile, increasing in response to chronic pain (Brandt & Livingston, 1990; Dickenson, 1995), and changing with age (Marsh et al., 1997). In both brain and spinal cord, a new receptor has been identified which although sharing a high degree of sequence similarity with opioid receptors is not activated by opioids. This receptor was named the ORL-1 (opioid receptor-like) receptor. Subsequently the endogenous peptide ligand for ORL-1 was identified and named orphanin FQ or nociceptin. This peptide has a widespread distribution throughout the nervous system. Despite its structural similarity to opioid peptides, nociceptin (which has now been synthesized) appears to work through entirely different neurological pathways, and it is thought that these pathways might be involved in the modulation of a broad range of physiological and behavioural functions (Meunier, 1997; Darland & Grandy, 1998). In the midbrain the ORL-1 receptor type has a dense to moderate level of expression in the periaqueductal gray matter, an area known to be involved with nocioceptive processing, and where electrical stimulation or opioid agonist agents will produce intense analgesia (Meunier, 1997; Darland & Grandy, 1998). In the spinal cord of the rat, ORL-1 receptors are found in the superficial layers (laminae 1 and 2) of the dorsal horn, in areas similar to those where opioid receptors are located. The density of neurones expressing the ORL-1 receptor varies in different areas of the spinal cord. The most recent work (unpublished results quoted by Darland & Grandy, 1998) suggests that these neurones are internuncial neurones, and do not themselves project forward to the thalamus.

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