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Background  Translating efficacy of analgesic drugs from animal models to humans remains challenging. Reasons are multifaceted, but lack of sufficiently rigorous preclinical study design criteria and phenotypically relevant models may be partly responsible. To begin to address this fundamental issue, we assessed the analgesic efficacy of morphine in three inbred rat strains (selected based on stress reactivity and affective/pain phenotypes), and outbred Sprague Dawley ( SD ) rats supplied from two vendors.    Methods  Sensitivity to morphine (0.3–6.0 mg/kg, s.c.) was evaluated in the hot plate test of acute thermal nociception, the Complete Freund's Adjuvant ( CFA ) model of inflammatory‐induced mechanical hyperalgesia, and in a locomotor motility assay in male rats from the following strains; Lewis ( LEW ), Fischer (F344), Wistar Kyoto ( WKY ), and  SD 's from Envigo and Charles River.    Results  F344 and  SD  rats were similarly sensitive to morphine in hot plate and  CFA ‐induced inflammatory hyperalgesia (Minimum Effective Dose ( MED ) = 3.0 mg/kg).  WKY  rats developed a less robust mechanical hypersensitivity after  CFA  injection, and were less sensitive to morphine in both pain tests ( MED  = 6.0 mg/kg).  LEW  rats were completely insensitive to morphine in the hot plate test, in contrast to the reversal of  CFA ‐induced hyperalgesia ( MED  = 3.0 mg/kg). All strains exhibited a dose‐dependent reduction in locomotor activity at 3.0–6.0 mg/kg.    Conclusion  Sensory phenotyping in response to acute thermal and inflammatory‐induced pain, and sensitivity to morphine in various inbred and outbred rat strains indicates that different pathophysiological mechanisms are engaged after injury. This could have profound implications for translating preclinical drug discovery efforts into pain patients.    Significance  The choice of rat strain used in preclinical pain research can profoundly affect the outcome of experiments in relation to (a) nociceptive threshold responses, and (b) efficacy to analgesic treatment, in assays of acute and tonic inflammatory nociceptive pain.

european journal of pain

The analgesic efficacy of morphine varies with rat strain and experimental pain model: implications for target validation efforts in pain drug discovery