Differential cross-tolerance development between single and repeated immobilization stress on the antinociceptive effect induced by β-endorphin, 5-hydroxytryptamine, morphine, and WIN55,212-2 in the inflammatory mouse pain mode

Abstract

We have evaluated the possible underlying mechanisms of immobilization stress-induced analgesia (SIA) by behavioral cross-tolerance studies and molecular studies. In the behavioral studies, the cross-tolerance between single or repeated immobilization SIA and the antinociceptive effects of β-endorphin, morphine, 5-hydroxytryptamine (5-HT), or WIN55,212-2 were assessed. Both single and repeated (×7) immobilization stress significantly attenuated the β-endorphin and 5-hydroxytryptamine-induced antinociception in the 2nd phase of formalin response, respectively. However, these cross-tolerances disappeared in prolonged repetition of the stress (×14). Neither single nor repeated (×7 and ×14) immobilization stress affected the antinociceptive effect of morphine or WIN55,212-2 at all. We also found that immobilization stress activated hypothalamic proopiomelanocortin (POMC) gene and β-endorphin expression. Since, it has potent inhibitory activity on the noxious stimuli-induced POMC expression, immobilization stress seemed to dissipate the POMC gene expression process. Meanwhile, we did not find any changes in the opioid receptors' (mu-, delta- and kappa-receptor) and the cannabinoid receptors' (CB1 and CB2) expressions in the midbrain regions elicited by single or repeated stress. These results suggested that a single immobilization stress activates the descending pain modulatory system, which is mainly mediated through endorphinergic and serotonergic activation. Moreover, the tolerance of SIA induced by repeated stresses may be due to the prolonged activation of these systems induced by repeated immobilization.

Antidepressant‐like effects of BU10119, a novel buprenorphine analogue with mixed κ/μ receptor antagonist properties, in mice

“…This model may be complicated by stress‐induced changes in skin temperature arising from vasoconstriction, but this does not preclude an interpretation of stress‐induced analgesia (Butler and Finn, ). Acute stress has been shown to produce antinociception whereas prolonged or repeated exposure to the stress results in tolerance or even hyperalgesic responses (Gamaro et al, ; Seo et al, ; Seo et al, ). Different types of stressors including restraint, cold‐swim or presence of a predator can elicit opioid‐mediated stress‐induced analgesia, which activates distinct neuroanatomical structures (Keay and Bandler, ).…”

Brief Isolation Changes Nociceptive Behaviors and Compromises Drug Tests in Mice

“…showed that IT injection of oxytocin modulated spinal nociceptive transmission, in situations where the transmission was related to stress‐induced analgesia. In addition, the analgesia induced by stress from single immobilization is mainly mediated through serotonergic activation in the descending pain modulatory system …”

Significance of neuronal cytochrome P450 activity in opioid-mediated stress-induced analgesia

“…For forced swimming or foot shock, moderate water temperatures or low current intensities evoke opioid responses, whereas colder water or higher currents elicit non-opioid responses (Mogil, et al, 1996; Watkins and Mayer, Kelly, 1986). Presently, we used two well-characterized models of opioid-mediated, stress-induced analgesia: 1) restraint stress-induced analgesia (Amir and Amit, 1979;Porro and Carli, 1988;Kavaliers and Innes, 1987;Seo, et al, 2011), and 2) warm water swim stress-induced analgesia (Christie, et al, 1982;Kavaliers and Galea, 1995;Contet, et al, 2006;Mogil, et al, 1996;Rubinstein, et al, 1996). …”

“…Restraint stress was induced by methods similar to published studies (Kavaliers and Innes, 1992;Seo, et al, 2011). Subjects were tested for baseline nociceptive responses, injected with either naltrexone hydrochloride (10 mg/kg, i.p.)…”