Neurological dysfunction after intrathecal injection of dynorphin A (1-13) in the rat. I. Injection procedures modify pharmacological responses.
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)
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000008:administration & dosage / Q000494:pharmacology*; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D006614:Hindlimb / Q000294:innervation; D007278:Injections, Spinal; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009619:Nociceptors / Q000187:drug effects*; D010243:Paralysis / Q000139:chemically induced; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000187:drug effects
D010446:Peptide Fragments; D004743:Enkephalin, Leucine; C026843:dynorphin (1-13); D004399:Dynorphins; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine