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Neuropeptide Y is a regulatory peptide found in adrenergic and non-adrenergic neurons. Diabetes, which may cause autonomic neuropathy, induces an increase in hypothalamic neuropeptide Y (NPY) levels; thereby we measured the effects of chronic diabetes on neuropeptide Y in the intestine. Rats were injected with streptozotocin (65 mg/kg) and maintained for up to 20 weeks. Another group of rats was injected with 6-hydroxydopamine (50 mg/kg) x 2 to induce sympathectomy. Ileum and colon were harvested and both whole and microdissected intestine were (1) stained with antibodies to neuropeptide Y, vasoactive intestine polypeptide, and neurofilaments or (2) extracted for neuropeptide Y radioimmunoassay. Neuropeptide Y levels were similar under all conditions in the colon, but there was a trend toward an increase in the diabetic whole ileum. NPY levels were significantly increased in the dissected myenteric plexus ileal layer in diabetics. We noted an increase in the number of neuropeptide Y and vasoactive intestine polypeptide immunoreactive myenteric neurons in diabetics and after 6-hydroxydopamine-induced sympathectomy. Diabetes, and to a lesser extent sympathectomy, induced an increase in ileal neuropeptide Y levels and neuropeptide Y-staining myenteric but not submucosal neurons. Altered tissue levels of neuropeptide Y may account for certain of the gastrointestinal disturbances commonly seen in diabetes.

The effect of ketorolac, a parenterally administered, nonsteroidal anti-inflammatory drug, was examined in a rat model of postoperative ileus. Small intestinal transit was measured by calculating the geometric center (GC) of distribution of 51CrO4. Laparotomy significantly delayed transit (GC: 2.2 +/- 0.2 after laparotomy versus 5.6 +/- 0.5 for unoperated controls, p < 0.01). The administration of ketorolac (1 mg/kg) improved the GC to 5.2 +/- 0.2 (p < 0.01), indicating normal intestinal transit after surgery in ketorolac-treated animals. Small intestinal myoelectric activity was recorded in rats with implanted electrodes. Animals treated with saline 2 hours postoperatively did not show return of the migrating myoelectric complex (MMC) in 183 +/- 25 minutes. In contrast, rats receiving ketorolac postoperatively had return of MMC activity in 59 +/- 18 minutes (p < 0.01). Preoperative ketorolac treatment reduced the duration of MMC inhibition after surgery from 197 +/- 55 minutes to 13 +/- 5 minutes (p < 0.05) when compared with saline. In summary, ketorolac hastens the return of MMC activity when given postoperatively. When ketorolac is administered preoperatively, it completely prevents the delay in intestinal transit and the inhibition of myoelectric activity seen in postoperative ileus. We concluded that ketorolac may be of benefit in the prevention and treatment of postoperative ileus.