Intrathecal somatostatin in the guinea pig: effects on spinal cord blood flow, histopathology and motor function.
In the present investigation, the vasoconstrictive, motor and neurodegenerative effects of intrathecal somatostatin (SST) were assessed in guinea pigs implanted with lumbar intrathecal catheters. Five consecutive dose increments of SST (5, 10, 15, 30 and 60 micrograms) to a total of 120 micrograms during the period of 16 +/- 3 min, resulted in a moderate (< 20%), gradual decrease of the spinal blood flow monitored with the laser-doppler method. A subsequent injection of clonidine (50 micrograms) or norepinephrine (10 micrograms) resulted in a more pronounced decrease of spinal blood flow (35% and 79%, respectively). Three consecutive, daily intrathecal injections of 30 or 60 micrograms SST did not cause any loss of weight support or paralysis of the hind limbs. There were no histopathological changes in the white or gray matter of the thoracic and lumbar sections of the spinal cords. It is concluded that SST, in the doses studied, is not neurodegenerative in guinea pigs. These findings are in contrast to those previously seen in rats. The implication of this study may be the necessity to use several alternate animal species in order to evaluate the antinociceptive and neurodegenerative properties of the peptides administered by the intrathecal route and the choice of dose to be compared across species.
Department of Anesthesiology and Intensive Care, Örebro Medical Center Hospital, ÖrebroSweden Astra Alab AB, Research and Development Laboratories and Astra Toxicological Laboratories, SödertäljeSweden.
Peter
P
Mollenholt
Claes
C
Post
Ivar
I
Paulsson
Narinder
N
Rawal
D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006651:Histocytochemistry; D007278:Injections, Spinal; D017078:Laser-Doppler Flowmetry; D008297:Male; D009474:Neurons / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects; D013004:Somatostatin / Q000008:administration & dosage / Q000494:pharmacology*; D013116:Spinal Cord / Q000033:anatomy & histology / Q000098:blood supply* / Q000187:drug effects
D013004:Somatostatin; D003000:Clonidine; D009638:Norepinephrine