Most people have some idea of what chronic pain is, but how exactly is chronic pain defined? Chronic pain is defined as any intermittent or persistent pain that lasts more than 3 months. This pain can be categorized as nociceptive or neuropathic, among other things. Nociceptive pain is the result of a threatened or true damage of nonneural tissue, whereas neuropathic pain is induced by abnormalities of the nervous system. Furthermore, there are close correlations between pain and depression in terms of neurological functioning and brain regions. One important factor in chronic pain causing depression is the common neuroplasticity changes seen in both chronic pain and depression.
In this post, we will be discussing and summarizing the article, “The Link Between Depression And Chronic Pain: Neural Mechanisms In The Brain.”
(Disclaimer: I am not a medical professional and all information provided in this post is from the article which is available in the “references” section at the bottom of the page. This post is meant only to provide a synopsis of the information covered in the original article.)
Introduction
It has been observed that patients who suffer from chronic pain-induced depression have a worse prognosis than those who have chronic pain only. There are close correlations between depression and chronic pain as well as their ability to mutually worsen each other. Studies have shown that chronic pain often causes depression and that up to 85% of patients who experience chronic pain also suffer from severe depression.
Recent studies have shown overlaps between depression-and-pain-induced neurobiological mechanisms and neuroplasticity changes. The injury sensory pathways that transmit body pains have been found to share the same regions of the brain that are involved in mood management. These brain regions include the amygdala, thalamus, hippocampus, insular cortex, anterior cingulate, and prefrontal cortex. The sharing of these brain regions creates a histological structural foundation for the co-occurrence of depression and pain.
Along with this, it has been seen that the hippocampus and prefrontal cortex are smaller in depressed patients with size correlating to depression severity. Not only is the prefrontal cortex seen to be smaller, but there also seems to be a reduction in the number of prefrontal cortex synapses in depressed individuals. Furthermore, maladaptive plasticity changes also play a part in chronic pain.
Cliff Notes
Recent evidence has shown a link between depression and chronic pain. It has been observed that sensory receptors operate in the same regions that work to control mood. Furthermore, it has been seen that depression shrinks these brain regions, suggesting that as depression worsens, so does pain. In summary, pain worsens depression and depression worsens pain.
Molecular Mechanisms Associated With Chronic Pain And Depression
Monoamine neurotransmitters such as norepinephrine, serotonin, and dopamine have been studied concerning depression and chronic pain. One hypothesis is that depression occurs as a result of decreased availability of monoamine neurotransmitters within the central nervous system. Along with this, monoamine neurotransmitters play an important role in the development of chronic pain.
Chronic pain has been shown to potentially damage dopamine activity significantly within the limbic midbrain. The dopamine system within the limbic midbrain has been observed to be less reactive in chronic pain patients.
Brain-derived neurotrophic factor is involved in the signaling pathways of the hippocampal dentate gyrus and the prefrontal cortex as well as in neuroplasticity regulation. Depression has been found to reduce the levels of brain-derived neurotrophic factors in the bloodstream as well as decrease the expression and function of brain-derived neurotrophic factors in the hippocampus and prefrontal cortex. Furthermore, brain-derived neurotrophic factor is involved in hypersensitivity to pain and also influences the progression of neuropathic pain.
In recent decades, a link has been found between the central nervous system and inflammatory factors. Inflammatory responses have been shown to cause depression and pain. This suggests that depression may be more strongly associated with inflammatory response-mediated pain.
One of the main excitatory neurotransmitters in the brain is called glutamate. Glutamate is involved in the occurrence of depression and pain. The excitatory and inhibitory effects of glutamate within the spinal cord are involved in central hyperalgesia (increased pain sensitivity) and pathological pain.
Cliff Notes
Neuroplasticity plays a crucial role in the development and occurrence of depression and chronic pain and could involve the same signaling pathways, brain structures, and neurotransmitters.
Opioids For Depression And Chronic Pain
As the most effective drugs for treating chronic pain, opioids are used for things such as neuropathic pain, cancer pain, and nociceptive pain. Opioids may achieve antidepressant effects by regulating the neurotransmitter systems. They can also serve to inhibit the release of dopamine to help relieve emotions.
It has already been established that opioids show potential for treating chronic pain, however, they are controversial as a treatment for depression because of the risks of addiction/dependence. Long-term opioid use has been seen to cause increased pain sensitivity and an increased risk of depression. Additionally, it has been seen that patients with a history of depression had to take opioids for three times longer than patients without depression.
Benzodiazepines have demonstrated therapeutic effects in treating chronic pains such as inflammatory or neuropathic pain. The pain-relieving mechanisms of benzodiazepines may be associated with the antihyperalgesic (reduction and pain sensitivity) effects of the GABAA receptors. These findings indicate that benzodiazepines may help treat chronic pain-induced depression.
Cliff Notes
Opioids are an effective method for treating chronic pain. However, there are risks with opioid-based treatments due to addiction/dependence issues. That being said, opioids may help treat chronic pain-induced depression because they reduce pain and promote the regulation of neurotransmitter systems.
Antidepressants For Chronic Pain Treatment
Clinical depression is associated with decreased levels of serotonin and norepinephrine within certain regions of the central nervous system. Monoamine oxidase inhibitor may work as an antidepressant by increasing the levels of serotonin and/or norepinephrine in these central nervous system regions.
The traditional antidepressants are known as tricyclic antidepressants and include drugs such as desipramine, amitriptyline, nortriptyline, and imipramine. Recent years have seen an increase in studies focused on the impacts of tricyclic antidepressants on pain management. It has been shown that, due to similar neuroplasticity changes within the monoamine neurotransmitter system in pain and depression, antidepressants may be useful for pain management. Serotonin and norepinephrine reuptake inhibitor antidepressants have been confirmed to be effective for chronic neuropathic pain patients.
Studies have shown that glutamate and its NMDA receptor subtypes play a role in pain reduction and antidepressant therapy. Ketamine, which influences NMDA receptors, has been used for anesthetization for over 40 years and has been reported to rapidly reduce depressive symptoms. Thus, it has become an antidepressant drug designed to target the glutamatergic system. However, these drugs have severe side effects such as restlessness, dry mouth, poor coordination, blurred vision, nausea or vomiting, headache, and dizziness. As a result of this, the safety of NMDA receptor-based antidepressants needs to be studied further.
Cliff Notes
Much like opioids can treat depression, antidepressants can treat pain. Because of the similar effects of pain and depression on the brain, both types of drugs work to treat the other condition (opioids for depression, antidepressants for pain). Essentially, antidepressants may work to relieve pain by increasing the levels of serotonin and norepinephrine within the central nervous system.
Summary
All of this can get a bit confusing, but basically, there is a link between depression and pain. Depression and pain both impact the same areas of the brain and therefore, their impacts and treatment are closely intertwined. If you are treating one, you are treating the other. Opioids and antidepressants have both been found to be effective in treating chronic pain and depression because they impact the same brain regions. The good news is, if you are treating your pain it will help your depression, and if you are treating your depression you will be treating your pain.
References
Sheng, Jiyao, et al. “The Link between Depression and Chronic Pain: Neural Mechanisms in the Brain.” Neural Plasticity, U.S. National Library of Medicine, 2017, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5494581/.
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