Regional analgesic effect of epidural morphine in volunteers

Abstract

Limb ischaemia induced by a sub-maximum effort tourniquet technique was used to characterize the analgesic effects of lumbar epidural morphine in volunteers. As an index of pain threshold, we measured the time to perception of pain in an upper and a lower limb before and at intervals up to six hours following epidural injections of morphine 3.5 mg and 7.0 rag, and before and after subcutaneous injections of the same doses. Subcutaneous morphine had no significant effect on the times to perception of pain in either limb. Lumbar epidural morphine did not alter upper limb times, but markedly delayed the onset of pain in the lower limbs. This lower limb analgesic effect was apparent thirty minutes after injection, peaked at about ninety minutes and was still present after six hours. Serum levels of morphine were nearly identical after subcutaneous and epidural injections of the same dose. We conclude that lumbar epidural morphine produces marked analgesia for this type of experimental pain primarily by a "'regional" effect rather than as a result of systemic absorption. This regional effect develops slowly and is prolonged.KEY WORDS: ANALGESIA, Epidural morphine, regional effect.ALTHOUGH A SPINAL ACTION of narcotics had been suspected for many years, ~ it was only recently discovered that small doses of narcotic placed directly into the sub-arachnoid space of animals could produce behavioural analgesia,-' apparently by binding to specific receptors in the dorsal horn of the spinal cord, 3.~ and so reducing central transmission of peripheral noxious stimulP -x.Both intrathecal and epidural morphine have now been carefully tested for analgesic effectiveness in human patients with pathological pain. In double-blind cross-over studies employing placebo controls, lumbar intrathecal morphine 0.5-1.0 mg was observed to relieve severe "'intractable" pain associated with cancer of the pelvis, ~ and lumbar epidural morphine 2-6 mg to reduce pain after upper abdominal surgeryJ ~ In each case. the quality of analgesia was better than that associated with commonly used intramuscular doses of morphine. 9'~~ For extended analgesic therapy, the epidural route of administration would be preferred to the intrathecal, as it avoids the added risks associated with repeated subarachnoid punctures.There is only limited information on the pharmacokinetics and pharmacodynamics of epidurally administered narcotic. Preliminary data suggest that after epidural injections of morphine and meperidine in man, narcotic appears in the lumbar cerebrospinal fluid (CSF) within minutes, with local CSF concentrations becoming maximal in about 30 minutes. TM The analgesia produced is reported to be "regional" or "segmental" in nature, ~3-~5 but its onset, magnitude and duration are unclear, seeming to vary considerably between individual patients -perhaps partly dependent upon the origin and type of pain being treated and, in some instances, the clinical condition in which pain has occurred. ~ :'t 6.~ 7The purpose of this study was to examine in a...

Effects of epidural administration of morphine and buprenorphine on the minimum alveolar concentration of isoflurane in cats

“…Onset of analgesic effect in humans has been repeatedly reported to be approximately 30 minutes after epidural morphine administration, with a peak effect at approximately 50 to 90 minutes. [29][30][31] The effect on MAC might, however, be independent of the analgesic effect and, therefore, have a different onset time. From published studies 11,12,22 that revealed an effect of morphine on MAC and in which onset can be assessed, it appears that onset occurred 30 to 100 minutes after administration.…”

The Rational Use of Intrathecal and Extradural Opioids

“…Similarly, extradural morphine 3.5 or 7.5 mg markedly delayed the onset of experimentally induced ischaemic pain in the lower limbs, but not in the arms. This effect was still present 6h after injection [185]. Subcutaneous morphine had no significant effect on the times to pain perception in either limb and the authors concluded that the extradural morphine produced analgesia by a regional effect rather than by systemic absorption.…”

Controlled Trial of Extradural Bupivacaine With Fentanyl, Morphine or Placebo for Pain Relief in Labour

“…In non-pregnant women, extradural morphine alone provides a long-lasting analgesia of slow onset. In pregnant women, extradural morphine alone, in a dose of 5 mg or less, is ineffective in providing satisfactory pain relief throughout labour [1,3,[5][6][7][8][9], probably because the extradural vascular congestion of pregnancy enhances vascular absorption of morphine [18][19][20][21][22][23][24]. Several investigators have reported that extradural bupivacaine improves the quality of analgesia when administered after [9] or simultaneously with [12] extradural morphine during the first stage of labour.…”