The Opposite of Indifference to Pain

You have heard of those born with pain indifference. New work suggests they may have a defective Nav 1.7 sodium channel


Waxman and his group at Yale continue to amaze us with their elegant work on pain.

Most recently, Dib-Hajj et al, including Waxman, found that the sodium channel, Nav 1.7 (remember that Nav 1.3 is thought to be the primary culprit in Central pain, but Nav 1.7 is under suspicion as well) plays an important role in SEVERE pain.

As they say:

“Na(v)1.7 is expressed preferentially in most slowly conducting nociceptive neurons and in sympathetic neurons. Gain-of-function mutations in the Na(v)1.7 channel lead to DRG neuron hyperexcitability associated with severe pain, whereas loss of the Na(v)1.7 channel in patients leads to indifference to pain.”

Lidocaine and other pain drugs can have serious side effects on memory, motor, and brain function. As Dib-Hajj points out:

“…the absence of motor, cognitive and cardiac deficits in patients lacking [the Nav 1.7]… channel make it an attractive target for the treatment of neuropathic pain.”

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NaV means Voltage gated sodium ion channel. Voltage gated means it opens according to voltage rather than via a G protein coupling mechanism or metabotrophic mechanism.