Toxicological sciences : an official journal of the Society of Toxicology
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To define the effects of chronic spinal exposure to a highly selective partial differential opioid agonist c[DPen(2),DPen(5)]enkephalin (DPDPE), adult beagles were prepared with chronic lumbar intrathecal catheters. Groups of dogs received intrathecal infusions (100 micro l/h) of saline (vehicle), DPDPE 3 mg/ml or 6 mg/ml for 28 days. Over the 28-day period, saline or 3 mg/ml showed minimal changes in neurological function, whereas in the 6 mg/ml animals, prominent hind limb dysfunction evolved over the 28-day interval. ⋯ In separate animals, prepared with dual intrathecal catheters, lumbar CSF was sampled at specified time points following intrathecal bolus (3 mg/ml) and 24 h DPDPE infusion (3 mg/ml and 6 mg/ml). Steady-state cerebrospinal fluid (CSF) DPDPE levels were 18.6 +/- 1.0 and 22.6 +/- 4.0 micro g/ml for 3 mg/ml and 6 mg/ml infusions respectively. These results indicate that this partial differential opioid agonist DPDPE produces a concentration and time-dependent formation of an intrathecal inflammatory mass.