title: A dissociative change in the efficacy of supraspinal versus spinal morphine in the neuropathic rat.
abstract: The efficacy of spinally versus supraspinally administered morphine was studied in rats with a spinal nerve ligation-induced neuropathy. Behavioural assessment indicated that the effect of intrathecally administered morphine on pain-related responses was attenuated when compared with unoperated controls. The decreased efficacy of spinal morphine was associated with neuropathic symptoms, since sham ligation or nerve ligation without accompanying tactile allodynia did not lead to spinal inefficacy of morphine. In contrast, the pain attenuating effect of morphine in the periaqueductal gray (PAG) was enhanced in neuropathic animals. The effect of systemically administered morphine on pain-related behavior of neuropathic rats was in the same range as in controls or decreased, depending on the test. Coadministration of lidocaine or MK-801, a N-methyl-D-aspartate (NMDA) receptor antagonist, into the rostroventromedial medulla enhanced the tactile antiallodynic but not the thermal antinociceptive effect of intrathecally administered morphine in neuropathic animals. Supraspinal administration of MK-801 or lidocaine did not influence efficacy of spinal morphine in sham-operated animals. Electrophysiological recordings of nociceptive wide-dynamic range (WDR) neurons in the deep spinal dorsal horn of pentobarbitone-anesthetized animals corresponded to a large extent with behavioral results. The inhibitory effect of spinally and systemically administered morphine on WDR neuron responses was attenuated whereas that induced by morphine in the PAG was enhanced in neuropathic animals. The results indicate that in spinal nerve ligation-induced neuropathy the efficacy of spinal morphine is decreased whereas that of supraspinal morphine is increased. Descending influence from brainstem-spinal pathways, involving NMDA receptors in the rostroventromedial medulla, may contribute to the selective reduction in tactile antiallodynic efficacy of spinal morphine.
authors.affiliation: Department of Physiology, Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, FIN-20520 Turku, Finland Department of Physiology, Institute of Biomedicine, University of Helsinki, P.O. Box 63, FIN-00014 Helsinki, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Pertovaara
authors.forename: Hong
authors.initials: H
authors.lastname: Wei
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000627:therapeutic use; D000779:Anesthetics, Local; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006930:Hyperalgesia / Q000503:physiopathology; D007278:Injections, Spinal; D008012:Lidocaine / Q000494:pharmacology; D008026:Ligation; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects; D009020:Morphine / Q000008:administration & dosage* / Q000627:therapeutic use; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects; D010487:Periaqueductal Gray / Q000187:drug effects; D010812:Physical Stimulation / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology*; D013127:Spinal Nerves / Q000293:injuries / Q000503:physiopathology; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D000779:Anesthetics, Local; D018691:Excitatory Amino Acid Antagonists; D009292:Narcotic Antagonists; D009270:Naloxone; D016291:Dizocilpine Maleate; D009020:Morphine; D008012:Lidocaine