Naloxone and experimental spinal cord injury: Part 2. Megadose treatment in a dynamic load injury model.
We previously reported that high dose naloxone (10 mg/kg) failed to promote recovery of motor function after a static load injury of the spinal cord in rats. In the present experiments, using the more traditional dynamic weight drop model, we tested megadose naloxone administered by the intraperitoneal route in 23 rats, including saline controls (Experiment 1). Thirty minutes after a cord injury at T-12, naloxone was given i.p. in a bolus of 100 mg/kg, followed by a continuous i.p. infusion of 50 mg/kg/hour for 23 hours. Again, no benefit was observed; this raised a question regarding naloxone and its absorption and serum levels. In another study, reported separately, we found that naloxone administered by the subcutaneous route affords higher and more sustained serum levels than by i.p. administration. Consequently, in 20 rats (Experiment 2), we repeated the protocol, using subcutaneous naloxone in a bolus dose of 150 mg/kg, followed by continuous infusion of 75 mg/kg/hour for 23 hours; the result was again negative. Morphometric determination of the residual (normal) cross sectional areas of gray and white matter at the epicenter of the cord lesion showed no statistically significant difference between treated and control animals in either Experiment 1 or Experiment 2. In view of the negative findings at high dose (10 mg/kg) and megadose naloxone, it seems that a reasonable next step would be an evaluation of lower doses using a factorial research design, incorporating a range of doses of naloxone in relation to a variety of intensities of cord injury. This question will be addressed in future experiments.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D009048:Motor Skills / Q000187:drug effects; D009270:Naloxone / Q000627:therapeutic use*; D010264:Paraplegia / Q000188:drug therapy; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000473:pathology; D013117:Spinal Cord Compression / Q000188:drug therapy* / Q000473:pathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology; D014949:Wounds, Nonpenetrating / Q000188:drug therapy* / Q000473:pathology
D009270:Naloxone