Role of meningeal mast cells in intrathecal morphine-evoked granuloma formation.

Background: Intrathecal morphine forms granulomas that arise from the adjacent arachnoid membrane. The authors propose that these inflammatory cells exit the meningeal vasculature secondary to meningeal mast cell degranulation.

Methods: Three sets of experiments were accomplished in dogs: (1) ex vivo meningeal mast cell degranulation (histamine release was measured ex vivo from canine dura incubated with opiates); (2) in vivo cutaneous mast cell degranulation (flare areas on the dog abdomen were measured after subcutaneous opiates); and (3) in vivo granuloma pharmacology.

Toxicology profile of N-methyl-D-aspartate antagonists delivered by intrathecal infusion in the canine model.

Background: Intrathecal N-methyl-d-aspartate antagonists have antihyperalgesic efficacy. The authors examined toxicity in a canine model of chronic lumbar intrathecal infusion.

Methods: Dogs (10-16 kg) were prepared with lumbar intrathecal catheters connected to vest-mounted pumps (100 microl/h).

Development of a canine nociceptive thermal escape model.

Acute nociceptive models which have been validated for large animal species are limited, yet nociceptive assessment in non-rodent species is important in analgesic drug development where larger animals may be necessary because of the technical requirements of the study. Here we report development and validation of a canine hind paw thermal escape model and the effect of analgesics on withdrawal latencies. Individual focused projection bulbs were used as left and right voltage-adjusted thermal stimuli placed below a glass plate in a specifically designed canine holding apparatus.

Opiate pharmacology of intrathecal granulomas.

Background: Chronic intrathecal morphine infusion produces intradural granulomas. The authors examined a variety of opioids infused intrathecal for analgesic activity and toxicity.

Methods: Two sets of experiments were undertaken in dogs with chronic intrathecal catheters: (1) Six-hour intrathecal infusions were used to determine the full analgesic dose and the maximum tolerated dose.

Time course and role of morphine dose and concentration in intrathecal granuloma formation in dogs: a combined magnetic resonance imaging and histopathology investigation.

Background: Intrathecal morphine infusion leads to intrathecal granulomas. In dogs, the authors examined time course of granuloma formation and the role of concentration in granuloma development.

Methods: Dogs were prepared with lumbar intrathecal catheters and vest-mounted pumps.

Intrathecal ketorolac in dogs and rats.

This study was conducted to assess spinal safety of the cyclo-oxygenase inhibitor ketorolac in dogs and rats. Beagle dogs were prepared with lumbar intrathecal catheters and received continuous spinal infusions of 5 mg/ml ketorolac (N = 6), 0.5 mg/ml ketorolac (N = 8), or saline vehicle (N = 6) at 50 microl/h (1.

Chronically infused intrathecal morphine in dogs.

Background: Despite the extensive use of intrathecal morphine infusion for pain, no systematic safety studies exist on its effects in high concentrations. The authors assessed the effects of morphine and clonidine given 28 days intrathecally in dogs.

Methods: Beagles with lumbar intrathecal catheters received solutions delivered by a vest-mounted infusion pump.