SAN DIEGO, CALIFORNIA--Opioid drugs such as morphine are the most powerful painkillers. Unfortunately, in some patients their narcotic effects lead to addiction and the need for ever-escalating doses to quell pain. New research with rats shows that blocking morphine's action on glia--a type of support cell in the nervous system--can reduce these downsides while heightening its potency against pain.
Over the past decade, scientists have discovered that glial cells heighten nerve pain, such as sciatica, by exciting the neurons that transmit pain signals. Morphine deadens pain by acting at nerve synapses, but it also activates glial cells, possibly worsening the drug's side effects, such as drowsiness, tolerance, worsening of pain, and addiction.
To tease apart morphine's effects on glia and neurons, neuroscientists Linda Watkins and Mark Hutchinson of the University of Colorado, Boulder, took advantage of a drug called AV411 that blocks morphine's effects on glia but not on neurons. It boosted the painkiller: Rats injected with AV411 and morphine showed less response to a painful test than did rats given morphine alone. Watkins and Hutchinson also found that over time, morphine better retained its pain-relieving potency in the rats that also received AV411.
Doctors prescribe morphine for pain relief, but opioids come with the potential for addiction or abuse. To check for a link between glia and morphine addiction, the pair tested whether blocking morphine's effects on glial cells would keep rats from craving the drug. In this test, the pain-free animals learned that they would receive a drug in one area and not in another. Animals that enjoy receiving a drug tend to return to the drug area over and over. Rats in the AV411-plus-morphine group wandered around rather than returning to the drug area, the researchers reported here 5 November at the annual meeting of the Society for Neuroscience.
By showing that glial cells "play a previously unsuspected role in pathological pain," says Nora Volkow, director of the National Institute on Drug Abuse, the research helps pave the way toward developing new, potent, nonaddictive medications.