Researchers link microglia activation triggered by chronic pain to anxiety and depression.


Brain inflammation caused by chronic nerve pain alters activity in regions that regulate mood and motivation, suggesting for the first time that a direct biophysical link exists between long-term pain and the depression, anxiety and substance abuse seen in more than half of these patients, UC Irvine and UCLA researchers report. The opensource study is published in the Journal of Neuroscience.

The team state that the data findings also points to new approaches for treating chronic pain, which is second only to bipolar disorder among illness-related causes of suicide. About a quarter of Americans suffer from chronic pain, making it the most common form of enduring illness for those under the age of 60. The Institute of Medicine estimates that this costs the US economy more than $635 billion per year.

Using rodent animal models over five-years the team discovered that pain-derived brain inflammation causes the accelerated growth and activation of immune cells called microglia. These cells trigger chemical signals within neurons that restrict the release of dopamine, a neurotransmitter that helps control the brain’s reward and pleasure centers.  The results also show why opioid drugs such as morphine can be ineffective against chronic pain. Previous studies show that morphine and its derivatives normally stimulate the release of dopamine. However, the current study showed that these drugs failed to stimulate a dopamine response, resulting in impaired reward-motivated behavior.

The team found that treating these animals in chronic pain with a drug that inhibits microglial activation restored dopamine release and reward-motivated behavior.

The researchers state that for over 20 years, scientists have been trying to unlock the mechanisms at work that connect opioid use, pain relief, depression and addiction.  The team note that the current study represents a paradigm shift which has broad implications that are not restricted to the problem of pain and may translate to other disorders.

Next, the team aim to establish that pain-derived changes in human brain circuitry can account for mood disorders. The lab state that they have a drug compound that has the potential to normalize reward-like behaviour and plan to employ imaging studies to identify how the same disruption in reward circuitry found in rodents occurs in chronic pain patients.

Source:  University of California, Irvine

Chronic pain disrupts Cl− transport in VTA GABAergic through a microglia-BDNF signaling pathway.  KCC2 labeling in the VTA was primarily localized in processes not labeled for TH. Immunolabeling of KCC2 (green) was identified in non-TH (red)-labeled neurons and the labeling was punctate, which is indicative of terminal arborization. Scale bar, 75 μm. The right micrographs represent a single image of a TH+ neuron (middle, arrowhead) surrounded by KCC2-immunoreactive arbors (bottom). The top image is a merge of the bottom two images.  Microglia Disrupt Mesolimbic Reward Circuitry in Chronic Pain.  Cahill et al 2015.

Chronic pain disrupts Cl− transport in VTA GABAergic through a microglia-BDNF signaling pathway. KCC2 labeling in the VTA was primarily localized in processes not labeled for TH. Immunolabeling of KCC2 (green) was identified in non-TH (red)-labeled neurons and the labeling was punctate, which is indicative of terminal arborization. Scale bar, 75 μm. The right micrographs represent a single image of a TH+ neuron (middle, arrowhead) surrounded by KCC2-immunoreactive arbors (bottom). The top image is a merge of the bottom two images. Microglia Disrupt Mesolimbic Reward Circuitry in Chronic Pain. Cahill et al 2015.

 

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