Pain sensitivity is altered in animals after subchronic ketamine treatment

Rationale Clinical observations have shown that pain sensitivity is altered in some schizophrenic patients. Objectives To study alterations in pain sensitivity, the ketamine model in schizophrenia research was employed. Materials and methods Rats were subchronically injected with the dissociative anaesthetic ketamine (Ket, ten injections of 30 mg/kg, one injection per day over a period of 10 days). Two weeks after treatment completion, the animals' pain sensitivity was assayed in the hot plate test and they were subjected to electrical stimulation of the tail root. In addition, the effect of morphine was studied. Results In group-housed animals, there was no difference between Ket-injected animals and control rats as measured in both nociceptive tests. In singly housed Ket-injected rats, pain threshold was increased in the electrical stimulation test. This suggests that stress due to single housing might be essential for modifications of pain sensitivity. Moreover, the antinociceptive effect of morphine was modified after single housing. Interestingly, the effect of morphine on locomotor activity was similar in both groups. In group-housed rats, mu receptor binding was unchanged in the frontal cortex, whereas Ket-injected animals had decreased levels in the hippocampus. In singly housed animals, mu receptor binding in Ket-injected rats increased in the frontal cortex and decreased in the hippocampus. S-35-GTP gamma-S binding increased in the frontal cortex in both singly housed groups, but remained unchanged in the hippocampus. Conclusions The data suggest that the ketamine model might be useful for studying altered pain sensitivity in schizophrenia. Moreover, the data suggest that modifications in mu opioid receptor binding contribute to this phenomenon.