Compared with rats given saline, those that received morphine endured postoperative pain for over 3 additional weeks. Also, the longer the morphine was provided, the longer the rats' pain lasted.
The study also revealed that tapering of morphine dosage makes no difference. As Grace explains, "This tells us that this is not a phenomenon related to opioid withdrawal, which we know can cause pain. Something else is going on here."
The next question to ask, of course, is what drives this counterintuitive effect. Prof. Watkins calls it the result of a "one-two hit" on glial cells.
In the brain, glial cells are more numerous than neurons. They protect and support nerve cells and, as part of their role as protector, they direct the brain's immune response, including inflammation.
The first "hit" occurs when surgery activates glial cells' toll-like receptor 4 (TLR4). Prof. Watkins calls these "not me, not right, not O.K." receptors; they help to orchestrate the inflammatory response. This first hit primes them for action when the second hit occurs.
The second hit is morphine, which also stimulates TLR4. As Prof. Watkins explains:
"With that second hit, the primed glial cells respond faster, stronger, and longer than before, creating a much more enduring state of inflammation and sometimes local tissue damage."
Although the study is in an animal model and will need replic