Specific down-regulation of spinal mu-opioid receptor and reduced analgesic effects of morphine in mice with postherpetic pain.
The analgesic effects of opioid agonists and the expression of mu- and kappa-opioid receptors were compared between mice with herpetic pain and those with postherpetic pain induced by herpetic virus inoculation. Morphine inhibited herpetic pain more effectively than postherpetic pain. Intrathecal injection reduced the analgesic effects of morphine on postherpetic pain, but intracerebroventricular injection did not. The kappa-opioid receptor agonist nalfurafine suppressed herpetic and postherpetic pain to similar degrees. mu-Opioid receptor-like immunoreactivities in the lumbar dorsal horn were markedly decreased at the postherpetic, but not herpetic, stage of pain. In the dorsal root ganglia, the expression of mu-opioid receptor mRNA was significantly decreased in mice with postherpetic pain, whereas the kappa-opioid receptor mRNA level was not altered. These results suggest that specific down-regulation of the mu-opioid receptor in the primary sensory neurons is responsible for the reduced analgesic action of morphine on postherpetic pain. The kappa-opioid receptor may be a useful target for the analgesic treatment of postherpetic neuralgia.
Takasaki
Ichiro
I
Division of Molecular Genetics Research, Life Science Research Center, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Nojima
Hiroshi
H
Shiraki
Kimiyasu
K
Kuraishi
Yasushi
Y
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005260:Female; D005455:Fluorescent Antibody Technique; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D018259:Herpesvirus 1, Human; D006930:Hyperalgesia / Q000188:drug therapy; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D051379:Mice; D008807:Mice, Inbred BALB C; D009019:Morphinans / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology*; D051474:Neuralgia, Postherpetic / Q000188:drug therapy* / Q000235:genetics*; D010146:Pain / Q000523:psychology; D010147:Pain Measurement; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D017473:Receptors, Opioid, kappa / Q000819:agonists; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013131:Spine / Q000187:drug effects / Q000378:metabolism*; D013141:Spiro Compounds / Q000494:pharmacology
D000701:Analgesics, Opioid; D009019:Morphinans; D012333:RNA, Messenger; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D013141:Spiro Compounds; C111212:TRK 820; D009020:Morphine