Distinguishable effects of intrathecal dynorphins, somatostatin, neurotensin and s-calcitonin on nociception and motor function in the rat.
We determined the effects on nociceptive threshold and motor function of dynorphin-gene products, dynorphin A-(1-32) (DYN A-(1-32), DYN A-(1-8), DYN B and DYN B-29 and the non-opioid peptides somatostatin, neurotensin and salmon calcitonin (s-CT) after intrathecal administration in the rat. DYN A-(1-32) (25 nmol) produced maximal elevation of tail-flick latency accompanied by severe hind limb paralysis and tail flaccidity lasting 6 h and still present at 24 h in several animals. Antinociception evaluated by the vocalization test wore off within 2 h. A lower dose of the peptide (6.25 nmol) did not alter the tail-flick reflex and motor function but significantly elevated the vocalization threshold. The other dynorphins showed weaker, short-lasting activity on the nociceptive threshold, the order of potency being as follows: DYN B-29 greater than DYN B greater than DYN A-(1-8). On the other hand, at the high doses DYN B (100 nmol) and DYN B-29 (50 and 100 nmol) caused moderately severe hind limb paralysis whereas DYN A-(1-8) did not cause any motor impairment up to the dose of 100 nmol. MR 1452, a relatively preferential antagonist of the kappa opioid receptor, prevented both the antinociceptive and motor effects of dynorphins. Intrathecal somatostatin (25 nmol) had a profile of activity superimposable on that of DYN A-(1-32): long-lasting (up to 24 h) elevation of tail-flick latency with hind limb paralysis, and a shorter (4 h) elevation of the vocalization threshold. MR 1452 did not modify these effects. Intrathecal neurotensin (25 nmol) and s-CT (0.5 nmol) did not alter tail-flick latency or vocalization threshold. However, adopting the hot plate as the analgesimetric test, both peptides elevated the time of hind paw licking, taken as an index of nociception. No signs of motor dysfunction were observed at the doses employed.
Spampinato
Santi
S
Institute of Pharmacology, University of Bologna, 40126 BolognaItaly.
Romualdi
Patrizia
P
Candeletti
Sanzio
S
Cavicchini
Emanuela
E
Ferri
Sergio
S
D000818:Animals; D002116:Calcitonin / Q000494:pharmacology*; D004399:Dynorphins / Q000494:pharmacology*; D007278:Injections, Spinal; D008297:Male; D009068:Movement / Q000187:drug effects*; D009496:Neurotensin / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects*; D010146:Pain / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000494:pharmacology*; D013997:Time Factors
D009496:Neurotensin; D013004:Somatostatin; D004399:Dynorphins; C028815:salmon calcitonin; D002116:Calcitonin