Neurology Central

Study identifies link between chronic pain-induced dopamine inhibition and mental illness

In a study recently published in The Journal of Neuroscience, Catherine Cahill of the University of California, Irvine (CA, USA) and her colleagues discovered that chronic pain accelerated neuroinflammation, and thus the growth and activation of microglia in the ventral tegmental area of the brain. These immune cells were discovered to disrupt chloridehomeostasis in GABAergic neurons, resulting in a restriction of the release of dopamine, which plays a key role in reward-motivated behaviour, pleasure and regulating emotional responses.

The high comorbidity of depression in patients with chronic pain is an area of concern among clinicians; chronic pain is second only to bipolar disorder as the main cause of suicide among all medical illnesses. This highlights the need to understand the biophysical link between chronic pain and the anxiety, depression and drug abuse exhibited in more than half of its sufferers.

Using rodents as a model system, Cahill and her team were able to demonstrate that peripheral nerve injury leads to activated microglia within reward circuitry, disrupting dopamine signaling and reward behaviour. Treating the chronic pain group with a drug that inhibits microglial activation restored chloride transport within these GABAergic neurons, re-establishing dopamine-dependent reward behavior.

Furthermore, the study also suggested a potential theory that explains why morphine can be ineffective in the treatment of chronic pain. In the control group, systemic morphine induced an increase in extracellular dopamine as expected; however, morphine failed to promote an increase in this neurotransmitter in the group subjected to chronic pain, impairing reward-motivated behaviour. Cocaine was also demonstrated to reduce ability to evoke dopamine release in the chronic pain group.

Cahill commented: ”For over 20 years, scientists have been trying to unlock the mechanisms at work that connect opioid use, pain relief, depression and addiction.” She added, ”Our findings represent a paradigm shift which has broad implications that are not restricted to the problem of pain and may translate to other disorders.”

Cahill and her team hope to build upon this research to prove that pain-derived changes in human brain circuitry can account for mood disorders.

Source: Taylor AM, Castonguay A, Taylor A et al. Microglia disrupt mesolimbic reward circuitry in chronic pain. J. Neurosci. 35(22), 8442–8450 (2015); University of California, Irvine