Apparent lack of tolerance in the formalin test suggests different mechanisms for morphine analgesia in different types of pain.

Tolerance to morphine analgesia was examined using the Formalin test in which pain lasting about 2 hrs associated with minor tissue injury is produced by subcutaneous injection of dilute Formalin. To distinguish behavioral from pharmacological tolerance, different groups of rats received their daily morphine injection (7 mg/kg) in the test environment or in their home environment for 5 days. Another group of rats was given morphine for 15 days in the home cage followed by 5 days in the test environment. None of the morphine injected groups differed from saline injected control groups in the amount of analgesia. These findings add to previous evidence that the Formalin test measures a type of pain which is different from that assessed in withdrawal reflex tests, and which more closely resembles clinical pain in man. Moreover, the fact that analgesia in the Formalin test shows little tolerance while analgesia in withdrawal tests shows rapid tolerance suggests that the underlying neural mechanisms are different.