In the second of two blogs looking at future possibilities for pain relief we turn to a much feared arthropod.
A friend of mine coping with severe back pain, allodynia, high blood pressure and fibromyalgia happened to bump into a scorpion in a shower while down in Mexico. With her blood pressure skyrocketing (scorpion venom increases blood pressure), and her pain hurling towards a 9-10 on a 10 point scale, she considered curling up on the floor, and letting someone discover her body the next day. She picked herself up, though, went to a clinic and then took every pain and sleeping medication she could.
She woke up the next day exhausted with a huge surprise; the worst pain she dealt with on a day to day basis, the pain she had no answer to – the allodynia stretching down the top of her right thigh – was significantly reduced. (Allodynia is a condition in which even the slightest touch of a fabric on the skin can cause pain.)
Over time the pain did come back but it took awhile and some digging suggested her surprising pain relief was no accident. If an Israeli researcher has his way, it may not take a scorpion bite to ease intractable nerve pain in the future.
Dr. Michael Gurevitz of Tel Aviv University is determined to find a way to turn a scorpion’s sting into a balm for pain sufferers. Remarkably, the same bite that causes pain, irritability, hyperthermia, vomiting, profuse salivation, tremor, and convulsion and sometimes even organ damage and death could hold the key to pain reduction.
Bioengineered scorpion toxins have been monumental to the evolution of channel science, and are now serving as templates for the development of invaluable experimental molecular therapeutics. http://www.ncbi.nlm.nih.gov/pubmed/23202307
The key to that, Gurevitz, a much published researchers on scorpion toxins, believes, lies in the scorpion venom’s ability to impact the ion channels in the body. It turns out that scorpion venom is exquisitely focused on the ion channels; in fact, scorpion venom based probes have played a critical role in elucidating sodium, calcium and potassium channel structure. (Check out a 75-page review paper on scorpion venom and potassium channels for some good late-night reading.)
Sodium ion channels are Gurevitz’s target. Of the nine sodium channels in the body, two (Nav 1.7, 1.8) are responsible for delivering pain signals to the brain. These channels, found in both the central nervous system and in the small diameter neurons (remember small fiber neuropathy?) found in the dorsal root ganglia in the body could hold the key to the problem of pain sensitization.
The Dorsal Root Ganglia – the Key to Chronic Pain?
A recent Martinez-Lavin study that directly implicates mutated sodium channels in the dorsal ganglia with severe pain in fibromyalgia suggests Gurevitz is on the right track. Martinez-Lavin believes sodium channels on the dorsal root ganglia hold the key to FM, and we’ll explore his theory more later.
The nodules of the dorsal root ganglia, which lie alongside the spinal cord, contain cell bodies whose small nerve fibers (dendrites) extend to the skin, muscles, tendons and joints. Sodium channels in these ganglia are both pain and autonomic nervous system ‘gatekeepers’, and sodium channelopathies are associated with several painful disorders including erythromelalgia. One mutation appears to increase ‘pain perception’ by causing the DRG neurons to become ‘hyperexcitable’.
Dorsal root ganglia ‘hyper-excitability’, Martinez-Lavin believes, is causing the pain in fibromyalgia and chronic fatigue syndrome. They are the place where physical, emotional, or infective stimuli are translated into chronic pain in fibromyalgia, chronic fatigue syndrome and similar disorders.
(The dorsal root ganglia, which gather the sensory data from the body before it gets to the spinal, are also a prime target for the herpesviruses that may be operative in ME/CFS and FM. Shapiro proposes herpesvirus infection of the dorsal root ganglia causes chronic fatigue syndrome.)
Ion channelopathies have been proposed in chronic fatigue syndrome with the ciguatera toxin able to cause many symptoms similar to both ME/CFS and FM.
“If we figure this out, we may be able to slightly modify such toxins, making them more potent and specific for certain pain mediating sodium channels,” Prof. Gurevitz.
Gurevitch believe that finding the right scorpion venom peptide (from hundreds), and then tweaking it to turn those sodium channels off may spell safe effective pain relief. Since the drug would mimic a naturally occurring substance that simply washes out of the body it should be safe. Because it would stop over-active sodium channels from sending pain signals to the brain there would be no need to bludgeon the opioid receptors in the central nervous system to reduce the perception of pain.
Gurevtiz’s Israeli team is reportedly now developing scorpion-based compounds to combat pain. A drug is still a ways off. First comes the drug itself, then the animal studies and finally the human trials. The approach, if successful, though, could potentially spell relief for many with intractable pain problems.
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