On the other hand if a person has a sunburn, a light touch that would not normally cause pain may suddenly hurt a great deal. In that case, the potassium channels in dorsal horn neurons are less active, and they can't interfere with the transmission of pain signals to the brain.
The researchers tested the role of Kv4.2 in damping down the pain response by studying knockout mice that had no Kv4.2 gene. The mice were bred so that some pups in a litter were knockout mice while others were normal, wild-type mice with the gene. Knockout mice withdrew their paws from a heat source or mechanical stimulus more quickly than their wild-type siblings.
The scientists also looked at dorsal horn neurons in culture from both wild-type and knockout mice and found that the neurons from the knockout mice fired more readily than neurons from wild-type mice.
"That's because the inhibitory Kv4.2 channel was gone in the knockout mice," Gereau says. "It's hard to say that these mice somehow sense pain more intensely, but their thresholds for withdrawal from heat and touch are much lower than their brothers and sisters that are genetically normal."
Potassium channels in dorsal horn neurons are regulated by a molecule called extracellular signal-related kinase (ERK). Past research has demonstrated that if ERK activity is inhibited, much of the spinal cord's sensitivity to pain can be diminished. But scientists haven't really known what ERK was doing.
In this study, the research team looked for targets that might interact with ERK, and the potassium channel Kv4.2 happened to be one of those potential targets. They studied dorsal horn neurons from mice to clarify the relationship between ERK and Kv4.2.
"When an injury occurs, there is a massive barrage of activity in pain-sensing neurons, and as those neurons fire, that causes
Contact: Jim Dryden
Washington University School of Medicine