Comparison of subcutaneous and spinal subarachnoid injections of morphine and naloxone on analgesic tests in the rat

Small catheters were chronically implanted subdurally in the rat so that repeated microinjections could be made into the subarachnoid space at the lumbar area. Morphine, injected intrathecally (i.th.) produced analgesia as measured by the tail-flick test at doses $\text{1}\text{100}$ of those by the subcutaneous (s.c.) route. Analgesia from i.th. morphine was reversed by either i.th. or s.c. injected naloxone. The dose of naloxone by the i.th. route was about $\text{1}\text{30}$ of that by the s.c. route. However, i.th. injection was no more effective than s.c. injection of naloxone in reversing analgesia produced by s.c. injection of morphine. When [³H]-labelled naloxone was injected s.c. or i.th. in the above experiment of morphine antagonism, there was a more rapid entry of the labelled material in the brain by the i.th. route of administration. The results raise questions on the relative importance of the spinal mechanism of analgesia produced by s.c. injections of morphine. Analgesia was also measured by the tail-shock vocalization test in which morphine producd a dose-dependent elevation of shock threshold at s.c. doses above those prolonging tail-flick latencies. Morphine injected i.th. at doses above those which elevated tail-flick latency produced hypersensitivity, hyper-reflexia, and convulsive seizure of the hindquarters. The spinal analgesic effect of morphine, when administered localy, appears to have a low ceiling of efficacy.