Analgesia from a peripherally active κ-opioid receptor agonist in patients with chronic pancreatitis

Preclinical studies suggest that visceral afferents constitutively express κ-opioid receptors (KORs) and that noxious visceral stimuli can be inhibited at a peripheral site by KOR activation. To test the relevance of these observations to humans, we infused, in a randomized, double blind manner, a peripherally selective KOR agonist (ADL 10-0101) or placebo into six patients with chronic pancreatitis and ongoing abdominal pain despite μ-opioid agonist therapy. Pain was assessed using a pain magnitude estimate, an open ended scale of each patient's choosing and compared to their rating of pain from a 1.6 cm 2 thermode applied to the skin and heated to 49°C for 5 s. Normalizing pain scores to this rating as 100, pain prior to study drug treatment was 40 70, and was unaffected by placebo infusion in the two individuals receiving this therapy. In contrast, ADL 10-0101 infusion reduced pain score from 63±7.6 (mean±SE) prior to infusion to 23±15 4 h after infusion ( P