Molecular link between chronic pain and depression identified.

Chronic pain is defined as any persistent pain which lasts more than 3 months, with research indicting over 85% of patients suffering from chronic pain are affected by severe depression. Consequently, these patients exhibit a poorer prognosis than patients suffering from chronic pain alone. Numerous studies show the coexistence of chronic pain and depression tends to further aggravate the severity of both disorders, however, the brain mechanism for this is unclear.

Now, a study from researchers at Hokkaido University identifies the brain mechanism linking chronic pain and depression in rats. The team states their research could lead to the development of new treatments for chronic pain and depression. The study is published in The Journal of Neuroscience.

Previous studies show the mesolimbic dopamine system comprises neurons in the ventral tegmental area (VTA) and substantia nigra (SN), projecting to the ventral striatum. The mesolimbic dopamine system is associated with the rewarding effects of food, sex, and drugs of abuse in the brain.

Notwithstanding, aversive stimuli, such as pain, also stimulate dopamine, further diminishing the hypothesis dopamine is solely a reward-based signal. Therefore, dysfunction in the mesolimbic dopaminergic system has been implicated in both chronic pain and depression. The current study shows the mesolimbic dopaminergic system is suppressed during chronic pain which causes depression.

The current study utilizes an electrophysiological technique to measure the activities of neural pathways after four weeks of chronic pain in rats. Results show persistent chronic pain causes changes in the neuronal pathway projecting from the brain region called the bed nucleus of the stria terminalis (BNST) to the VTA.

Data findings show enhanced signaling mediated by corticotropin-releasing factor (CRF). Specifically, CRF is a neuropeptide known to be involved in the negative emotions such as anxiety and fear, in the BNST of chronic pain animals.

Results show this enhanced CRF signaling leads to suppression of the brain reward system, the mesolimbic dopamine system. The lab explains the suppression of the reward system is considered to be an underlying mechanism of depression, which leads to decreased pleasure and motivation.

They go on to add by clarifying the mechanism by which the brain reward system is continuously suppressed, they have identified the missing link between chronic pain and depression.

The team surmises they have identified the neural pathways linking chronic pain with depression in an animal model. For the future, the researchers state their findings could lead to improved treatment of the emotional aspect of chronic pain, as well as new therapeutics for depressive disorders.

Source: Hokkaido University

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