Have we missed the miracle painkiller?

How a classic pain scale would look to a person with congenital insensitivity to pain.
How a classic pain scale would look to a person with congenital insensitivity to pain.

Pain insensitivity has been introduced to the larger public via TV shows from the medical drama genre (House, ER, Gray’s Anatomy, and the like). It seems fascinating to explore the consequences of a life without pain. But these shows do not feature, quite understandably, the gruesome aspects of this rare and incredibly life threatening disorder. For example, did you know that sometimes the baby teeth of these people are extracted before they reach 1 year old so they stop biting their fingers and tongues off? Or that a good portion of the people born with pain insensitivity die before reaching adulthood?

Nahorski et al. (2015) discovered a new disorder that includes pain insensitivity, along with touch insensitivity, cognitive delay, and severe other disabilities. They investigated a family where the husband and wife are double first cousins and produced offsprings. The authors had access to all the family’s DNA, including the children. Extensive analyses revealed a mutation on the gene CLTCL1 that encodes for the protein CHC22. This protein is required for the normal development of the cells that fell pain and touch, among other things.

Other genetic studies into various syndromes of painlessness have produced data that lead to discovery of new analgesics. Therefore, the hope with this study is that CHC22 may become a target for a future painkiller discovery.

But, on the side note, what made me feature this paper is more than just the potential for new analgesics; is in the last paragraph of the paper: “rodents have lost CLTCL1 and thus must have alternative pathway(s) to compensate for this. Thus, some pain research results generated in these animals may not be applicable to man” (p. 2159).

The overwhelming majority of pain research and painkiller search is done in rodents. So…. how much from what we know from rodents and translate to humans doesn’t really apply? Worse yet, how many false negatives did we discard already? What if the panaceum universalis has been tried already in mice and nobody knows what it is because it didn’t work? It’s not like there is a database of negative results published somewhere where we can all ferret and, in the light of these new discoveries, give those loser chemicals another try…. Food for thought and yet ANOTHER reason why all research should be published, not just the positive results.

Reference: Nahorski MS, Al-Gazali L, Hertecant J, Owen DJ, Borner GH, Chen YC, Benn CL, Carvalho OP, Shaikh SS, Phelan A, Robinson MS, Royle SJ, & Woods CG. (August 2015, Epub 11 Jun 2015). A novel disorder reveals clathrin heavy chain-22 is essential for human pain and touch development. Brain, 138(Pt 8):2147-2160. doi: 10.1093/brain/awv149. Article | FREE FULLTEXT PDF

By Neuronicus, 20 October 2015