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Differential expression of tolerance to hypothermia and mechanical analgesia in the guinea pig following chronic opioid versus cannabinoid exposure
Author(s) -
Maguma Hercules T.,
Taylor David A.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.744.2
Subject(s) - drug tolerance , pharmacology , analgesic , morphine , hypothermia , medicine , cross tolerance , in vivo , anesthesia , opioid , biology , receptor , microbiology and biotechnology
Studies using guinea pig longitudinal muscle‐myenteric plexus (LM/MP) have shown heterologous tolerance after chronic morphine (MOR) exposure and homologous tolerance after WIN55,212‐2 (WIN) exposure. Few studies have compared tolerance that develops to hypothermic and mechanical analgesic activity of opioids and cannabinoids with that of the LM/MP model. Tolerance was induced by MOR (7 day) or WIN (5 day) injection and assessed by challenge doses of WIN and MOR. Analgesia was assessed using paw pressure test and hypothermia by a rectal thermometer. Chronic MOR treatment produced tolerance to hypothermic and analgesic effects of MOR but not hypothermic effect of WIN. WIN treatment elicited tolerance to hypothermic effect of WIN and MOR, and analgesic effect of MOR. No analgesia was observed after WIN challenge, suggesting the paw pressure model may not be sensitive enough or WIN does not produce analgesia in the model. Results show that nature of tolerance in one model cannot be inferred to another even in the same species. Chronic MOR treatment produces heterologous tolerance in an in‐vitro model and homologous in vivo while WIN regimen elicits homologous tolerance in vitro but heterologous in vivo . This affirms the notion that nature of tolerance depends on model, drug, species, and regimen used. Data also suggest that multiple cellular effects may induce differential functional tolerance in different models.