Systemic morphine treatment induces changes in firing patterns and responses of nociceptive afferent fibers in mouse glabrous skin.

摘要: Abstract Patients receiving opioids for pain may experience decreased effectiveness of the drug and even abnormal sensitivity—hyperalgesia and/or allodynia. We hypothesized that peripheral nociceptor hyperexcitability contributes to opioid-induced hyperalgesia tested this using an in vitro mouse glabrous skin-nerve preparation. Mice were injected intraperitoneally with escalating doses morphine (5, 8, 10, 15 mg/kg) or saline every 12 hours 48 hours killed approximately after last injection. Receptive fields nociceptors mechanical, heat, cold sensitivity. Activity was also measured during initial 2-minute period 5-minute periods between stimuli. Aberrant activity common fibers from morphine-treated mice but rare saline-treated mice. Resting background elevated C-fibers Both C- Aδ-fibers had afterdischarge response stimulation skin as well spontaneous, unevoked activity. Compared saline, treatment increased proportion displaying polymodal rather than mechanical-only responses. A significant increase Aδ-mechanoreceptive responding accounted most change. In agreement this, showed sensitivity tail flick test. mice, aberrant could contribute Importantly, is likely driving central sensitization, a phenomenon contributing sensory processing chronic pain. If similar changes occur human patients, be interpreted hyperalgesia.