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

Dale Hogan, Alyssa L. Baker, Jose A. Morón, Susan M. Carlton

    Research output: Contribution to journalArticlepeer-review

    12 Scopus citations


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

    Original languageEnglish (US)
    Pages (from-to)2297-2309
    Number of pages13
    Issue number11
    StatePublished - Nov 2013


    • Hyperexcitable
    • Opiate-induced hyperalgesia
    • Primary afferents
    • Spontaneous activity

    ASJC Scopus subject areas

    • Neurology
    • Clinical Neurology
    • Anesthesiology and Pain Medicine


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