Specific down-regulation of spinal μ-opioid receptor and reduced analgesic effects of morphine in mice with postherpetic pain

The analgesic effects of opioid agonists and the expression of μ- and κ-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 κ-opioid receptor agonist nalfurafine suppressed herpetic and postherpetic pain to similar degrees. μ-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 μ-opioid receptor mRNA was significantly decreased in mice with postherpetic pain, whereas the κ-opioid receptor mRNA level was not altered. These results suggest that specific down-regulation of the μ-opioid receptor in the primary sensory neurons is responsible for the reduced analgesic action of morphine on postherpetic pain. The κ-opioid receptor may be a useful target for the analgesic treatment of postherpetic neuralgia.