Cross-tolerance between antinociception induced by swim-stress and morphine in formalin test

Abstract

The present study investigated cross-tolerance between antinociception induced by water swim-stress and morphine in the formalin test. Intraperitoneal administration of morphine (3, 6 and 9 mg/kg) induced dose-dependent antinociception in both phases of the formalin test. Mice treated with a lower dose of morphine (25 mg/kg), once daily for 3 days, showed tolerance to antinociception induced by a lower test dose of morphine (3 mg/kg). Similar repeated treatments with a higher dose of morphine (50 mg/kg) produced tolerance to antinociception induced by different test doses of morphine (3, 6 and 9 mg/kg). Exposure to water swim-stress, once daily for 2 or 3 days in order to induce tolerance, also decreased morphine-induced antinociception. Swim-stress exposure for 2 or 3 days also tends to potentiate tolerance induced by a lower dose of morphine. Acute swim-stress of different durations (0.5, 1 and 3 min) induced antinociception in both phases of the formalin test, which was not reduced by naloxone, but showed even more antinociception in the second phase. The response to swim stress was decreased in mice treated with higher doses of morphine, but not those animals that received swimming stress (3 min) once daily for 2-3 days, in order to induce habituation to swim-stress-induced antinociception. The results may indicate a possible cross-tolerance between antinociception induced by morphine and by swim stress.

Enhanced anxiolytic and analgesic effectiveness or a better safety profile of morphine and tramadol combination in cholestatic and addicted mice

“…We proposed that alone administration of morphine or tramadol, as well as coadministration of them, together resulted in the activation of µ-opioid receptors as well as activation of catecholamine and serotonergic receptors [1,46,47] which caused an analgesic effect in cholestatic and addicted mice. This is in agreement with other studies that the administration of morphine and tramadol produced an antinociceptive effect through the activation of µ-opioid receptors [48][49][50].…”

Shared Mechanisms for Opioid Tolerance and a Transition to Chronic Pain

“…Because stress-induced hyperalgesic priming exhibited PKCε-dependence similar to the PKCε-dependence that we now know is shared by inflammation-induced and opioid-induced priming, we predict that interactions among stress, inflammation, and opioids at the level of primary afferent intracellular signaling pathways may contribute to the generation of opioid-resistant chronic pain states. Consistent with this idea, stress-induced analgesia can be cross-tolerant with morphine-induced analgesia (Lewis et al, 1981; Girardot and Holloway, 1984; Szikszay and Benedek, 1989; da Silva Torres et al, 2003; Fazli-Tabaei et al, 2005). Thus, interaction among stress, opioids and hyperalgesic priming at the level of the primary afferent nerve ending may be important in pain patients in which all three factors often co-exist.…”

Endogenous opioid function mediates the association between laboratory-evoked pain sensitivity and morphine analgesic responses

“…Animal studies suggest that EO function does influence opioid analgesic responses, although direction of these effects appears inconsistent. While several animal studies indicate possible cross-tolerance between EOs and opioid analgesic medications 22,36,48 , others suggest synergistic effects, with direct application of EOs (e.g., beta-endorphin) or manipulations that trigger release of EOs (e.g., forced swim, tail suspension, exercise) enhancing responsiveness to opioid analgesics 2,5,12,13,17,31,46,47,49,50 . Human PET imaging findings are indirectly supportive as well, indicating that a placebo manipulation with EO enhancing effects 20 increases opioid analgesic responses 4 .…”