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.