The Corpus Callosum

A Pakistani boy who could walk on burning coals propelled drugmakers on a quest for the ultimate pain treatment that can ease an ailment as old as life itself without harmful side effects.
    
Geoffrey Woods, a geneticist at the University of Cambridge, was studying families that had intermarried in northern Pakistan when he heard about the boy, who felt no pangs as he performed stunts on the street. Research on other children in the area uncovered a faulty gene among them. They all were healthy and had a normal sense of touch...
    
...The sodium 1.7, or Nav1.7, channel is a protein found in nerve cells. When a cell receives a stimulus, the tube-like channel opens and sodium ions flow into it, activating the nerves. They send an electrical signal to the spinal cord and the brain, which interprets it as pain.
    
In people with the gene mutations found in the Pakistani children, the sodium channel is incomplete, interrupting the chemical cascade that leads to pain sensation.
    
Early research on the channel, first identified in the mid- 1990s, had found gene mutations that heightened the sense of pain. Woods's work, funded by Pfizer, the University of Cambridge and the London-based Wellcome Trust, was the first to establish a link between loss of the channel and an absence of distress...

It turns out that there are several types of sodium channels found in neurons, but so far, it appears that Nav1.7 occurs primarily in the periphery.  This is thought to be important, because it lowers the risk of unintended or unwanted effects in the brain.

Naturally, several companies are rushing to find a way to exploit this finding.  

The complete absence of pain in the periphery does have consequences.  Many children with this condition end up with serious injuries.  (Thinking about by own behavior as a teenage boy, I probably would have ended up with all kinds of fractures, and I wasn't particularly rambunctious.)

The article is from Bloomberg, a financial site.  So they focus on the fact that a small pharmaceutical firm, Newron, has a new chemical entity that is in clinical development.  

Research & Drug Development Ralfinamide
    
Newron is developing ralfinamide, a unique New Chemical Entity that is believed to mediate analgesic and anti-inflammatory effects through the modulation of ion channels implicated in pain and the inhibition of substance P.
    
Newron recently reported excellent results for its compound ralfinamide in patients with Nerve Compression and Entrapment conditions, where neuropathic low back pain (NLBP) represents the most common indication and for which there are no approved drugs. Newron recently initiated a Phase IIb/III study with Ralfinamide in patients with neuropathic low back pain (NLBP).

    

Note that this drug has more than one mechanism of action.  In addition to acting on the sodium channel, it blocks Substance P.  I am extremely curious about this, because previously there have been suggestions that Substance P antagonists might have antidepressant effects.  I've heard that development in this area, by at least one major pharmaceutical firm, have not panned out.  Still, we are in a drought right now for new antidepressants with novel mechanisms of action.  We know that antidepressants often treat pain, so it would be interesting to see if a novel pain drug could be used to treat depression.

So long as we are speculating, let's imagine what would happen if this drug were to make it to market.  (Note that many drugs in phase II or even phase III trials are never marketed.)  One question would be: how quickly does it act?  Would we see football players leave the field with an injury, dose up on ralfinamide, and return to play?  Would endurance athletes take ralfinamide to try to improve their performance?  Would we see an increase in athletic injuries because of this kind of thing?  Sure we would, until sports programs added it to the list of compounds that are banned, and started to screen for it.  

And what about drug abuse?  Would there be a black market for an effective pain drug?  Sure.  But if it does not produce euphoria, would this really be drug abuse, or something else?  Would we see a huge drop in addiction to opioids?  That is what we hope for.  If that turned out to be the case, the societal cost of the other problems would be tiny in comparison to the benefit.  

Of course, the new drug would be expensive.  That would put insurance companies in the position of having to decide whether to cover a new, nonaddictive, expensive drug, instead of a cheap, but potentially addictive one.  What would they do?  If it is any indication, I've seen companies that won't cover Strattera (a nonstimulant drug for ADHD) but who do cover Adderall (an amphetamine, also used for AHDH).