Peripheral Neuropathic Pain

 

Peripheral neuropathic pain in Parkinson’s disease has been reported to be seven times higher than in a normal population.  It has variously been attributed to insufficient vitamin B-12, perhaps from long term used of levodopa replacement medications or even to levodopa itself causing demyelination of neurons that  transmit pain impulses. In another disease, Charcot-Marie-Tooth (CMT) disease it results from a genetic mutation.  The principle of the cause of this demyelination process  in CMT has been identified and it is hoped that it will lead to treatments to alleviate this pain not only in CMT but Parkinson’s and other diseases as well.

Lawrence Wrabetz, M.D. and colleagues at the Hunter James Kelly Research Institute in Buffalo, New York, along with other European researchers have identified the mechanism by which proteins in the myelin sheath are mis-produced and found  the gene that also interferes in this mis-production process. The sheath is composed of Schwann cells  which produce myelin in nerve cells.  When the proteins that produce those cells begin synthesizing  mutated proteins, a gene called Gadd34 turns on and causes them to reproduce those mutated proteins at a much higher level, thereby increasing the problems in the myelination process.

Dr. Wrabetz’s team has also identified a way to improve myelin production with the addition  of a small molecule drug.  When salubrinal, a small molecule drug is added in both laboratory cultures and animal models of CMT Gadd34 is effectively reduced.  It partially turns off the protein syntheses process and helps restore myelination.

While Dr. Wrabetz disease model has been Charcot-Marie-Tooth disease, his main research has involved understanding myelination disorders in general.  He thinks that there may be one unifying underlying mechanism and that what applies to one disease may also apply to others.  If they are successful in finding a safe and effective dose for humans of salubrinal, the suffering from painful neuropathies will hopefully become a thing of the past.

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