Absence of morphine analgesia and its underlying descending serotonergic activation in an experimental mouse model of fibromyalgia

Mice exposed to intermittent cold stress (ICS), but not constant cold stress (CCS) showed sustained thermal hyperalgesia for up to 12 days. Systemic or intracerebroventricular (i.c.v.) injection of morphine caused no significant analgesia in ICS mice, but induced dose-dependent analgesia in control mice. However, significant analgesic effects were achieved by intrathecal or intraplantar injection of morphine. The i.c.v. injection of morphine significantly increased the turnover ratio (5-HIAA/5-HT) in the dorsal half of the spinal cord of control mice, but not in ICS mice. Collectively, these results indicate that the loss of descending serotonergic activation seems to be a key mechanism underlying the absence of morphine-induced analgesia.