Intrathecal dynorphin(1-13) results in an irreversible loss of the tail-flick reflex in rats.
Intrathecal injection of dynorphin produced a loss of the tail-flick reflex that lasted throughout the 14-day experimental period whereas, the inclined plane test of motor function and tail-shock vocalization recovered within an hour. An important aspect of the loss of the tail-flick reflex was that it was an all-or-none event. At any dose of tail-flick latency either remained unchanged when compared with pre-injection latencies or the latency was elevated to the cut off time of 14 s. The ED50's +/- S.E.M. for tail-flick, inclined plane and tail-shock vocalization were 65.4 +/- 5.0, 67.7 +/- 5.0 and 68.0 +/- 3.9 nmol respectively. Results from the hot-plate test revealed no statistical difference between saline and dynorphin injected animals one day following the injection. Animals injected with morphine sulphate s.c. lost the tail-flick reflex but completely recovered by 24 h. Histology of the spinal cord of animals treated with dynorphin 24 h prior to sacrifice revealed dead neurons primarily in the ventral horn with little or no damage in the dorsal horn. These data demonstrate that dynorphin(1-13) injected intrathecally results in a rather specific neurotoxic action in the spinal cord.
D000818:Animals; D004399:Dynorphins / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D007278:Injections, Spinal; D008297:Male; D009474:Neurons / Q000187:drug effects; D010146:Pain / Q000503:physiopathology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D014828:Vocalization, Animal
D010446:Peptide Fragments; C026843:dynorphin (1-13); D004399:Dynorphins