The experiments examined the characteristics of
analgesia produced by different doses of
morphine,
meperidine (
pethidine),
fentanyl, and
sufentanil after epidural and
subcutaneous injection in rats. The specificity of the
analgesia was also determined; other in vivo pharmacologic activities (i.e., blockade of pinna and cornea reflexes and production of skeletal muscle rigidity) were monitored as pharmacologic indices of
opiate drug activity in the brain. After
subcutaneous injection, the
opiates produced dose-dependent
analgesia, blocked the pinna and cornea reflexes, and induced
muscle rigidity. After
epidural injection, all four compounds produced dose-dependent
analgesia and had greater potency, earlier onset, shorter duration, and greater specificity of
analgesic action than was the case after
subcutaneous injection. Specificity is defined here as the ratio of the ED50 dose that blocked the pinna reflex to the ED50 dose that produced
analgesia. The gains in potency and specificity, but not the gains in onset time and the losses in duration of
analgesia, differed considerably among the compounds that were examined. The subcutaneous-to-epidural potency ratio related in a linear manner with the
lipid-to-water partition coefficient. The gain in specificity also appeared to be related to
lipid solubility. The microgram X kg-1 doses at which the
opiates produced
analgesia in rats correlate well with the potency of these compounds in producing
analgesia after
epidural injection in humans. The rat epidural preparation reflected the doses, onset, and specificity, but not the duration, of
analgesia produced by epidural
opiates in humans.