Today's post from sites.utoronto.ca (see link below) is a complex one for the lay reader but maybe you should give it a go anyway, even if you don't understand everything it says. The point is that it gives us as patients, an insight into how scientists are looking into our problems and trying to come up with solutions. It's like peeking through the keyhole and learning something new about what may be coming in the future, something which in itself can make us feel better about our condition because at least we know something is being done! Basically, the scientists here placed electrodes on the spinal cord at different places and measured the electronic activity of the nerve cells simultaneously. In this way they were able to identify where things were breaking down and could block nerve signals if they were causing pain. It's much more complex than this simplistic explanation of course but the potential for future treatments at source, using this sort of intervention, is enormous. Remember as long as you get a vague picture in your mind of what's going on, you're increasing your understanding of neuropathy at the same time.
Different Mechanisms of Spinal Cord Neuron Disinhibition in Neuropathic Pain Models Require Different Therapeutic Interventions
Posted on 18-09-2015
Exciting new research from Dr. Steven Prescott’s lab is working to bridge the gap between basic research on neuropathic pain etiology to possible clinical interventions to treat neuropathic pain. Dr. Steven Prescott is a UTCSP member and scientist at the Hospital for Sick Children. In this paper, lead author Dr. Kwan Lee uses a unique method to measure intact spinal cord neurons from alive, anaesthetized animals, overcoming disadvantages of ex-vivo methodologies. To do this, Dr. Lee placed an array of 16 recording electrodes into the superficial spinal cord, and was able to record the electrical activity of 16 neurons simultaneously.
Using this method, Dr. Lee found that two competing mechanisms of disinhibition (blockade of inhibition that yields net neuronal excitation) of these neurons yielded almost indistinguishable phenotypes, but were differentially sensitive to different pharmacological treatments. First, he blocked the potassium chloride co-transporter KCC2 using DIOA, which leads to a dysregulation of chloride in inhibitory neurons, and thus disinhibition. This resulted in allodynia in the animal, or an increase in response to a previously innocuous brush stimulus. Using the drug ACTZ, he was able to compensate for chloride dysregulation, and restore inhibition, bringing responses to brush stimulus back down to baseline.
Then, when Dr. Lee initiated disinhibition through blockade of GABAA receptors, again yielding increased neuronal responses to brush stimulus, ACTZ was not able to reduce these aberrant neuronal responses to previously innocuous brush stimuli. This indicates that two different forms of disinhibition that lead to the same measurable phenotype of neuropathic pain react differently to pharmacological interventions. This suggests that there should be a shift in the medical field to identifying biomarkers of neuropathic pain etiology or trying several potential treatments before selecting the specific therapeutic intervention for neuropathic pain patients, in order to best treat their symptoms.
To read this article, please visit: http://www.ncbi.nlm.nih.gov/pubmed/?term=26186265
Reference: Lee, KY, Prescott, SA. Chloride dysregulation and inhibitory receptor blockade yield equivalent disinhibition of spinal neurons yet are differentially reversed by carbonic anhydrase blockade. Pain. July, 2015.
http://sites.utoronto.ca/pain/research/articles/684.html
