MedicalResearch.com Interview with:
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: A great deal of preclinical work in animal models of pain has established that activation of peripheral immune cells or, in the central nervous system (brain and spinal cord), immune cells called “glia” (microglia and astrocytes) play a key role in the establishment and/or maintenance of persistent pain. For instance, if you pharmacologically block activation of these cells in the nervous system, you are able to reduce/inhibit/prevent pain behaviors, e.g. in animals who have received a nerve injury.
This observation is very exciting, because it suggests that blocking neuroinflammation may be a viable way of treating pain. However, the evidence linking human chronic pain with neuroinflammation has so far been limited.
In this study we show, for the first time, that patients with chronic sciatica (that is, back pain that shoots down the leg) demonstrate elevations in the levels of a protein called the translocator protein (TSPO) in the spinal cord and in the nerve roots.
Because TSPO is a marker of neuroinflammation, our results suggest that sciatica is associated with neuroinflammation.
While on average patients do show elevations in the levels of the TSPO, we also saw significant variability across individuals. Importantly, patients that show stronger elevations (in the nerve roots) were those who benefit the most from receiving a local anti-inflammatory treatment (epidural spinal injection). This makes sense: patients whose nerve roots are inflamed benefit from an anti-inflammatory treatment. Those whose nerve roots aren’t inflamed, don’t receive the same benefit. In the latter case, the source of the inflammation and pain may not be the nerve roots, but may be the spinal cord, or, as we showed in a previous paper (Loggia et al., Brain 2015), the brain.
MedicalResearch.com: What should readers take away from your report?
Response: The main message of the study is that, for the first time, we are showing evidence of neuroinflammation in patients with sciatica. This suggests that therapies targeting neuroinflammation (e.g. immune cells in the central and peripheral nervous systems) may be beneficial for patients with sciatica. Current treatments for sciatica, and chronic pain in general, are not very effective for many patients, and have heavily relied on the use of opioids. Research like ours suggests that alternative treatment mechanisms (e.g. targeting immune activation) may useful for chronic pain, and could be more effective for the large number of patients that do not respond to currently available therapeutics. However, there is a lot more work and validation to be done before treatments such as these are widely available.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: First and foremost, the current results represent a cross-sectional study from a relatively small group of representative patients and control subjects. While we assume that our findings are representative, at least in part, of the general population, our work will need to be replicated in larger groups.
That being said, this work also opens up exciting new opportunities for future studies. In fact, we are actively conducting a clinical trial in chronic low back pain patients with a therapy that inhibits immune cells in the brain and spinal cord (glial cells). It will be very interesting to see if this therapy is able to effectively inhibit these cells in pain patients, and whether that leads to a reduction in pain.
Our results in the paper also suggest that directly treating neuroinflammation in the spinal cord may help sciatica patients who don’t respond to steroid injections. Finding a way to treat spinal neuroinflammation for those patients is a goal that we are actively pursuing.
No disclosures to add.
Daniel S. Albrecht, Shihab U. Ahmed, Norman W. Kettner, Ronald J.H. Borra, Julien Cohen-Adad, Hao Deng, Timothy T. Houle, Arissa Opalacz, Sarah A. Roth, Marcos F. Vidal Melo, Lucy Chen, Jianren Mao, Jacob M. Hooker, Marco L. Loggia, Yi Zhang. Neuroinflammation of the spinal cord and nerve roots in chronic radicular pain patients. PAIN, 2018; 159 (5): 968 DOI: 1097/j.pain.0000000000001171
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