Summary: Blocking dorsal root ganglion pain neurons from releasing microRNA-21 has an anti-inflammatory effect at the cellular level, preventing neuropathic pain, researchers report.
Source: King’s College London.
New research from King’s College London has revealed a previously undiscovered mechanism of cellular communication, between neurons and immune cells, in neuropathic pain.
The authors, who published their findings today in Nature Communications, identified a new method of treating neuropathic pain in mice, which could be more safe and effective than current treatments comprising of opioids and antiepileptic drugs.
Neuropathic pain is a type of chronic pain that is usually caused by an injury to nerves, but the pain persists long after the injury has healed. Neuropathic pain may occur after surgery or a car accident, or in some cases when a limb has been amputated.
Currently the only available drugs for neuropathic pain are either opioids or antiepileptic medication. Opioids, like morphine and tramadol, are highly addictive and the NHS have recently raised concerns about prescription of these drugs, due to opioid overdoses more than doubling in the last decade. In the US an opioid ‘epidemic’ has recently been declared due to the rising number of deaths linked to these drugs. In contrast, antiepileptic medication is not addictive but is often accompanied by a whole host of unpleasant side effects such as dizziness, fatigue, nausea and weight gain.
However, people with neuropathic pain have very little choice when it comes to other treatment options because the cause of neuropathic pain is so poorly understood.
Using cellular and mouse models of neuropathic pain the authors studied a cluster of neurons in the dorsal root ganglion (DRG), which are part of the sensory neurons that play an important role in communicating pain information to the brain. They found that after nerve injury, pain neurons in this area released very small biological particles containing microRNA-21. These particles were then taken up by surrounding immune cells, ultimately leading to local inflammation and neuropathic pain.
The authors showed that when they blocked DRG pain neurons from releasing microRNA-21 in particles, this had an anti-inflammatory effect at a cellular level, which prevented neuropathic pain from occurring in mice. The advantage of this method is that these particles, containing agents that block microRNA-21, do not infiltrate the brain and lead to side effects.
In humans, a similar method could be applied to block pain neurons from releasing microRNA-21 in particles, which would prevent neuropathic pain from ocurring. If successful, this would be the first drug to target neuropathic pain in specific areas without side effects, which is in stark contrast to the non-specific painkillers currently available.
Fortunately, similar treatments are already being trialled in cancer patients receiving immunotherapy, making the application to other conditions like neuropathic pain highly feasible.
Professor Marzia Malcangio, senior author from the Wolfson Center for Age-Related Diseases at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King’s College London, said ‘If new treatments based on the findings of this study, targeting microRNA-21, could be designed for patients with neuropathic pain this could provide a brand new avenue for drug treatment. Our next steps are to explore whether the same mechanism applies to other chronic pain conditions.’
Funding: This study was funded by the European Commission FP7 grant.
Source: Jack Stonebridge – King’s College London
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Full open access research for “Exosomal cargo including microRNA regulates sensory neuron to macrophage communication after nerve trauma” by Raffaele Simeoli, Karli Montague, Hefin R. Jones, Laura Castaldi, David Chambers, Jayne H. Kelleher, Valentina Vacca, Thomas Pitcher, John Grist, Hadil Al-Ahdal, Liang-Fong Wong, Mauro Perretti, Johnathan Lai, Peter Mouritzen, Paul Heppenstall & Marzia Malcangio in Nature Communications. Published online November 24 2017 doi:10.1038/s41467-017-01841-5
Exosomal cargo including microRNA regulates sensory neuron to macrophage communication after nerve trauma
Following peripheral axon injury, dysregulation of non-coding microRNAs (miRs) occurs in dorsal root ganglia (DRG) sensory neurons. Here we show that DRG neuron cell bodies release extracellular vesicles, including exosomes containing miRs, upon activity. We demonstrate that miR-21-5p is released in the exosomal fraction of cultured DRG following capsaicin activation of TRPV1 receptors. Pure sensory neuron-derived exosomes released by capsaicin are readily phagocytosed by macrophages in which an increase in miR-21-5p expression promotes a pro-inflammatory phenotype. After nerve injury in mice, miR-21-5p is upregulated in DRG neurons and both intrathecal delivery of a miR-21-5p antagomir and conditional deletion of miR-21 in sensory neurons reduce neuropathic hypersensitivity as well as the extent of inflammatory macrophage recruitment in the DRG. We suggest that upregulation and release of miR-21 contribute to sensory neuron–macrophage communication after damage to the peripheral nerve.
“Exosomal cargo including microRNA regulates sensory neuron to macrophage communication after nerve trauma” by Raffaele Simeoli, Karli Montague, Hefin R. Jones, Laura Castaldi, David Chambers, Jayne H. Kelleher, Valentina Vacca, Thomas Pitcher, John Grist, Hadil Al-Ahdal, Liang-Fong Wong, Mauro Perretti, Johnathan Lai, Peter Mouritzen, Paul Heppenstall & Marzia Malcangio in Nature Communications. Published online November 24 2017 doi:10.1038/s41467-017-01841-5