Check out what an enterprising fibromyalgia and pain researcher is doing, how the immune system is involved in pain, and the most exciting pain research going on in an overview of an interview the Pain Research Forum did with Claudia Sommer, MD.
Claudia Sommer, MD is a busy woman. The director of the Peripheral Nerve Laboratory at the University of Wurzburg in Germany, she investigates the role cytokines and antibodies play in producing pain, is working to standardize diagnostics in neuropathy. She also treats fibromyalgia patients and people with neuropathic pain. She has training in psychiatry, neuropathology, anesthesia and neurology.
Over the past couple of years she’s been focused on fibromyalgia which she characterized as a “very difficult pain syndrome”. She noted that many of her colleagues still don’t believe fibromyalgia exists, while others believe it’s a somatoform disorder.
She was one of the first researchers to elucidate the small fiber neuropathies found in fibromyalgia. Like others, the finding of the nerve damage in the skin of fibromyalgia patients surprised. One of the exciting thing about the small fiber neuropathy finding in FM is that they’re an antidote to the naysayers asserting FM does not exist. Something is causing those nerve fibers in the skin to disappear.
“Even those who do believe that it exists say it’s very enigmatic and that we don’t know why fibromyalgia patients are in pain, and so finding that there is actually pathology in the periphery is very exciting. Claudia Sommer
Skeptics still abound though. It’s going to take some time to convince FM is real.
So there is still skepticism, and it’s going to be a long way before we can convince everyone, but the more we work toward finding physiological abnormalities in fibromyalgia patients, the more we will be able to sway our colleagues. Claudia Sommer
Stating that her lab has seen “many patients” and is continuing to study them more and more she’s apparently been hooked by the SFN problems she’s found in FM. With little doubt now remaining that SFN is present in a significant percentage of FM patients Sommer is trying to figure out what’s “burning up” those nerves. With her strong focus on the immune system she went after the pro-inflammatory cytokines. A 2014 study, however, suggested cytokines were not the answer for the SFN in FM.
They might be for other types of pain found in fibromyalgia, however. Instead of pro-inflammatory cytokines being high in FM they found low levels of anti-inflammatory and pain reducing cytokine called IL-4. Perhaps pain causing cytokines don’t need to be high if pain-reducing cytokines are low.
The finding was strong enough for them to “build” a mouse model that doesn’t produce any IL-4. The dorsal horn of the spinal cord plays a major role in pain sensitization in FM and other pain conditions. If low IL-4 levels change how the dorsal horn functions then boosting IL-4 levels might reduce pain in FM.
Sommer noted in a recent paper the modest effects most drugs prescribed for fibromyalgia have. Most drugs cause a 30% reduction in pain in half of FM patients and a 50% reduction in pain in about a third. These improvements do not translate into global improvements in well-being, and many patients who experience initial improvements will later drop the drugs because of side effects or reductions in effectiveness. Placebo effects may account for up to 60% of the drugs apparent effectiveness (as well as its perceived harms). The medical world has a long way to go to build effective FM drugs.
In a section titled “Hope for a Magic Bullet” Sommer covered some newer, mostly poorly studied treatment options but no magic bullets. (She did note that many other drugs are in the early stages of exploration in FM).
Growth hormone – improved pain and fatigue but high costs and side effects were an issue.
- Cannabinoids – Nabilone is a synthetic formulation of tetrahydrocannabinol, a factor found in cannabis (marijuana). While one small trial suggested nabilone was more effective than placebo in reducing pain and improving sleep another did not. Side effects were common. A recent National Pain Report survey, however, suggested that medical marijuana may be far more effective than any of the FDA-approved drugs for FM
- Quetiapine – Quetiapine is a short-term antipsychotic that enhances serotonin and dopamine levels and reduces sympathetic nervous system functioning. Several studies suggest quetiapine may be helpful but side effects particularly fatigue, are again an issue, as are concerns about the long-term use of the drug.
- Low Dose Naltrexone – was superior to placebo in reducing pain and improving mood but did not improve fatigue or sleep. More study is needed.
- Tackling Pain and Depression in Fibromyalgia: Quetiapine Scores Some Benefits in Clinical Trial
- Low Dose Naltrexone Resource Center
Immune Mediated Pain
Sommer has also been engaged in understanding immune system causes of pain. Pro-inflammatory cytokines were clearly been associated with pain in animal models, but the situation is more complex in humans. Sometimes high pro-inflammatory cytokine levels translate to pain and sometimes they don’t. Sometimes they are present and sometimes they’re not.
Pro-inflammatory cytokines cause pain when injected in one area and deaden pain when injected in another. It’s clear that blocking pro-inflammatory cytokines can reduce pain in rheumatoid arthritis but it does nothing for low back pain.
Higher levels of the pro-inflammatory cytokine IL-6 as well as IL-10 in skin biopsies of patients with peripheral neuropathy experiencing pain could explain why some peripheral neuropathies are painful and others are not.
Stiff Person Syndrome – Autoimmunity is becoming an ever more interesting topic in pain. Stiff Person Syndrome appears to be largely an immune-mediated disease of GABA deficiency. GABA – a feel good chemical in the central nervous system – is an inhibitory neurotransmitter that turns off the production of glutamate – an excitatory neurotransmitter.
In Stiff Person Syndrome (SPS) one’s muscles can instantaneously lock up – causing a person to suddenly fall over. People with SPS often experience severe muscle spasms and muscle stiffness so severe they have trouble moving. It’s an intriguing illness given the stiff muscles often found in fibromyalgia.
Deficient GABA signaling in the spinal cords of SPS patients leaves the motor system of the brain turned on – causing the muscles to go into spasm. SPS is an example of a pain disorder caused mostly by problems in the brain and spinal cord.
SPS appears to be largely caused by high levels of autoantibodies (GAD 65) to an enzyme involved in synthesizing GABA. This autoantibody, intriguingly enough, may underlie a wide variety neurological, metabolic and neuropsychiatric conditions that have been linked with GABA inhibition, including some speculate, fibromyalgia and ME/CFS.
Bearing close resemblance to a protein on a Coxsackie virus, the GAD antibody suggests all these conditions could have been triggered by an infection.
Peripheral Neuropathy – Peripheral neuropathy causes of the numbness, tingling and other nerve sensations common in FM and many other disorders. It has recently been associated with autoantibody attack of structures in the peripheral nerves called nodes of Ranvier.
Complex Regional Pain Syndrome – Autoantibodies to autonomic nervous system receptors in subset of patients with complex regional pain syndrome (CRPS) implicate autoimmunity in this disorder as well.
“Pharmaceutical investment in (voltage gated sodium channels) for pain therapeutics has expanded exponentially….Moreover, emerging clinical combined with recent breakthroughs in structural biology pave the way for a future of fruitful prospective drug discovery.” Bagal et. al.
Some of the most exciting pain research, however, concerns the work on ion channels. Sommer called the findings on voltage-gated sodium and TRP channels, “eye-openers” that could go a long way to explain mysterious cases of pain sensitization. These are small ion channels found on nerves that determine whether they get turned on or not. A mutation in one of these channels (channelopathy) could be sufficient to send pain-producing nerves into a frenzy.
The first channelopathy discovered caused burning pain that was triggered by increasing temperature in a condition called erythromelalgia. Similar channelopathies caused burning pain and flushing in a rare genetic condition called paroxysmal extreme pain disorder (PEPD). Other channelopathies can cause a complete cessation of pain. Most recently a channelopathy was found in about 30% of people with small fiber neuropathy.
There is still much to learn but with recent breakthroughs enabling a better understanding of how these channels function, pharmaceutical companies are now eagerly exploring drugs that can impact then.
Another possibility are microRNA’s that turn on or off genes associated with these channels. Sommer is currently involved in a large European study examining the effects mRNA’s may have on people in chronic pain.
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