Immobilization Stress Changed Some Pain-Drug Responses but Left WIN Responses Unchanged in Mice
Single and repeated immobilization stress altered selected antinociceptive responses in a mouse experiment, but did not affect the tested responses to morphine or WIN 55,212-2. Cross-tolerance was therefore not shared by every pain-modulating drug.
The comparison included different signaling systems
The researchers compared responses involving beta-endorphin, serotonin, morphine and a synthetic cannabinoid agonist in an inflammatory formalin model. Some stress histories attenuated beta-endorphin- and serotonin-induced antinociception during the second phase of the response. Those effects disappeared with a longer repetition schedule, showing that stress history mattered.
The cannabinoid null result belongs beside the positive findings
Neither single nor the tested repeated stress schedules affected WIN- or morphine-induced antinociception. Omitting these results would wrongly imply a general loss of drug responsiveness. The finding also does not show that stress can never influence cannabis effects: the experiment assessed a particular compound, species and inflammatory-pain endpoint.
Molecular findings did not show universal receptor change
The study reported stress-related POMC and beta-endorphin expression findings but no detected changes in the examined midbrain opioid- or cannabinoid-receptor expression measures. A behavioral adaptation can thus coexist with a null receptor-expression result. Expression, receptor function and behavior are different levels of observation.
Interpreting the evidence
This model supports selective stress-related cross-tolerance rather than a blanket cannabis-tolerance claim. Human psychological stress, THC intoxication and real-world function were not the outcomes tested.
Related reading: endogenous ligands administered as experimental drugs.
Research reference
Seo YJ; Kwon MS; Choi SM; et al. (2011). 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. Archives of pharmacal research. doi:10.1007/s12272-011-0213-1. Evidence basis: study abstract.
