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A Pain-Free Life: How Some People Are Unable to Feel Pain

Individuals born with a rare gene mutation that leads to a nonfunctional sodium channel Nav1.7 are unable to feel pain. Although previous attempts to develop an analgesic drug by blocking Nav1.7 have been largely unsuccessful, researchers at University College London discovered recently that Nav1.7-deficient humans and transgenic mice had elevated levels of opioid peptides. These opioids likely contribute to the painlessness and elucidate a potential analgesic approach that combines specific sodium channel blockade with a low dose of opioids.

Opioid drugs are effective for reducing pain, but long-term use can lead to dependence and tolerance. Also, broad-spectrum sodium channel blockers are not suitable for long-term pain management because they can cause serious side effects, including complete numbness. Patients with nonfunctional Nav1.7 can still feel non-painful stimuli, suggesting that a specific sodium channel blocker may reduce pain without causing other neurologic side effects. However, drugs that block Nav1.7 produced weak analgesic effects in previous studies. This led the researchers in the current study to investigate the mechanism responsible for pain development through Nav1.7. They found that mice and people lacking Nav1.7 produce higher-than-normal levels of natural opioid peptides, suggesting this may contribute to the painlessness experienced by these individuals.

To investigate the role of these opioids in eliminating pain, the researchers gave the transgenic mice naloxone, an opioid blocker, and showed that they were able to feel pain. Similarly, administering naloxone to a 39-year-old woman with nonfunctional Nav1.7 caused her to feel pain for the first time in her life. According to the researchers, these findings could be used to develop analgesic therapy that combines Nav1.7 blockade and low-dose opioid drugs, which would reduce the amount of opioids needed for pain relief.

Source: Minett MS et al. (2015) Endogenous opioids contribute to insensitivity to pain in humans and mice lacking sodium channel Nav1.7. Nature Communications 6: 8967.

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