Lumbar epidural morphine in humans and supraspinal analgesia to experimental heat pain.
BACKGROUND
Epidural administration of morphine is a common analgesic technique to manage pain. Morphine spreads from the epidural space to the cerebrospinal fluid and then rostrally, causing side effects mediated by the brain stem. However, data on the rostral spread of morphine-mediated analgesia are sparse. This study examined the rostral spread of analgesic effects on heat and electrical pain after epidural administration of morphine.


METHODS
In a randomized, double-blinded, placebo-controlled, crossover study, 5 mg morphine or saline placebo were injected into the lumbar epidural space in nine healthy volunteers. Correct needle placement was confirmed with fluoroscopy. Analgesia to experimental nociceptive heat and electrical stimuli was measured at lumbar (L4), thoracic (T10), cervical (C2), and trigeminal (V2) levels before and 2, 5, 10, and 24 h after epidural injection. Plasma samples for assaying morphine concentrations were drawn before and after each analgesic evaluation.


RESULTS
Epidural morphine significantly attenuated experimental heat pain at all dermatomes tested compared with saline placebo. Analgesic effects were significant at L4 after 2, 5, and 10 h, at T10 after 5, 10, and 24 h, and at V2 after 10 h. Electrical pain was attenuated at the lumbar and thoracic but not at the cervical dermatome. Analgesic effects were significant at L4 after 2, 5, and 10 h and at T10 after 5 and 10 h. Morphine plasma concentrations were below the detection limit (1 ng/ml) in eight of the nine subjects 10 h after epidural injection.


CONCLUSIONS
Lumbar epidural injection of morphine attenuated cutaneous heat pain up to the trigeminal dermatome during a 24-h observation period. In a clinical context, this implies that some types of pain may be attenuated up to the supraspinal level after lumbar epidural administration of morphine.
Angst
M S
MS
Department of Anesthesia, Stanford University School of Medicine, California 94305-5117, USA. ang@leland.stanford.edu
Ramaswamy
B
B
Riley
E T
ET
Stanski
D R
DR
D000328:Adult; D015360:Analgesia, Epidural; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001831:Body Temperature / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004558:Electric Stimulation; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006358:Hot Temperature; D006801:Humans; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy*; D017288:Pain Threshold / Q000187:drug effects
D000701:Analgesics, Opioid; D009020:Morphine