Naloxone and experimental spinal cord injury: effect of varying dose and intensity of injury.
We have reported previously that high-dose (10 mg/kg) and megadose naloxone (as high as 150 mg/kg) failed to promote recovery of motor function after spinal cord injury in rat. In view of these negative results, in comparison to some reports of benefit of naloxone in the literature, the present study was undertaken to assess lower doses, using a modified 3 x 4 factorial design, to evaluate a range of lower doses in relation to various intensities of cord injury. Sprague-Dawley rats were assigned randomly to 10 groups (n = 10) relating to two factors: intensity of injury and dosage of naloxone. A dynamic-load injury was induced with a 10-g weight dropped from a height of 2.5 cm, 5.0 cm, or 17.5 cm. Animals were treated with naloxone 1 mg/kg, 4 mg/kg, 10 mg/kg, or saline (control). Tests of motor recovery were carried out weekly for 4 weeks postinjury. Histopathological morphometric analysis of the spinal cords was carried out for measurement of residual gray and white matter at the epicenter of the cord injury. In general, the behavioral data showed no improvement in recovery of function, with the possible exception of naloxone at a dosage of 4 mg/kg (not statistically significant at 4 weeks). Independent of naloxone treatment, there was a significant difference among the three intensities of injury. Pathologically, a difference could not be demonstrated in relation to dosage of naloxone, but as in the case of the behavioral data, a graded response occurred as a function of intensity of injury.
Black
P
P
Department of Neurosurgery, Hahnemann University, Philadelphia, Pennsylvania.
Markowitz
R S
RS
Gillespie
J A
JA
Finkelstein
S D
SD
D000818:Animals; D004305:Dose-Response Relationship, Drug; D009043:Motor Activity / Q000187:drug effects*; D009270:Naloxone / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
D009270:Naloxone