In rats, the spinal subarachnoid injection of the kappa
opioid agonist
Dynorphin A (Dyn A)(1-13) and the
delta opioid receptor antagonist
ICI 174864 produced dose-related flaccid
paralysis of hindlimbs and tail that were influenced appreciably by injection procedures. When injected through indwelling intrathecal (i.t.)
catheters terminating at L1 to L2, both
peptides were significantly more potent producing
paralysis 1 day, rather than 10 to 14 days, after i.t. catheterization. Other rats received direct subarachnoid
injections of these
peptides through 30-gauge needles placed in the L4 to L5 intervertebral space. In naive, uncatheterized and acutely catheterized rats, direct intervertebral injection of these
peptides, as well as D-Ala2-Dyn A (1-13)
amide (a metabolically stable analog of Dyn A (1-13), produced hindlimb
paralysis with potencies comparable to those recorded after
injections through acutely implanted
catheters. In contrast, chronically catheterized rats showed significantly reduced responsivity to direct intervertebral
injections of all three of these
peptides. Loss of hindlimb motor function was associated with loss of nociceptive responsiveness. Elevations in tail-flick latencies were only seen with doses of Dyn A (1-13) which produced motor dysfunction, and were not blocked or reversed by high doses of the
opioid antagonist naloxone. These results indicate that: 1) indwelling i.t.
catheters induce spinal cord alterations which complicate their experimental usefulness, 2) Dyn A (1-13) does not alter responsiveness to thermal nociceptive stimuli through
opioid mechanism and 3) Dyn A (1-13) causes parallel disruptions of spinal cord motor and nociceptive function.(ABSTRACT TRUNCATED AT 250 WORDS)