Evaluation of acute and chronic nociception in subchronically administered MK-801-induced rat model of schizophrenia.

Abstract

Patients diagnosed with schizophrenia have been reported to exhibit atypically low pain sensitivity and to vary in their experience of chronic pain. To the best of our knowledge, there has yet to be an animal study that provides information concerning the relationship between models of schizophrenia and pain. In the present study, we investigated several distinct nociceptive behaviors in a translational rat model of schizophrenia (0. 5 mg/kg MK-801, twice a day for 7 days followed by a 7-day washout period). The presence of the expected cognitive deficit was confirmed with novel object recognition (NOR) paradigm prior to nociception testing. MK-801-treated rats with lack of novelty interest in NOR testing showed: hyposensitivity to thermal and mechanical stimuli; short-term hypoalgesia followed by augmented hyperalgesia in response to formalin-induced spontaneous nociception and increased thermal and mechanical hyperalgesia in the complete Freund's adjuvant (CFA) induced chronic pain model. In conclusion, MK-801 induced antinociception effects for thermal stimuli in rats that were consistent with the decreased pain sensitivity observed in schizophrenia patients. Additionally, the amplified biphasic response exhibited by the MK-801 group in the formalin-induced spontaneous nociception test affirms the suitability of the test as a model of acute to delayed pain transition.