20/04/2024
https://www.facebook.com/share/Zr23MwDzMwTVio3S/?mibextid=CTbP7E
Just published 🔥
Neuropathic Pain, Mood, and Stress-Related Disorders
👉 Neuropathic pain can be caused by multiple factors, and its prevalence can reach 7& of the global population (https://pubmed.ncbi.nlm.nih.gov/17888574/). It is becoming increasingly evident that limited or short-lasting response to treatments for neuropathic pain is associated with psychological factors, which include psychiatric comorbidities known to affect quality of life.( https://pubmed.ncbi.nlm.nih.gov/27586832/,
👉 It is estimated that 60% of patients with neuropathic pain also experience depression, anxiety, and stress symptoms (https://pubmed.ncbi.nlm.nih.gov/27344405/). Altered mood, including stress, can be a consequence of several painful conditions but can also favor chronification when preexisting. Despite the apparent tight connection between clinical pain and mood/stress disorders, the exact physiological mechanisms remain unclear.
💡 The following illustration by Vieira and colleagues (https://pubmed.ncbi.nlm.nih.gov/38614452/) summarizes some of the proposed psychoneuroimmunological mechanisms:
☑️ Left: The hypothalamic–pituitary–adrenal (HPA) axis plays a key role in maintaining body homeostasis and the body’s response to stress. Stress results in the release of corticotropin-releasing hormone (CRH) from the hypothalamus. This information is then transmitted to the anterior lobe of the pituitary gland, where the secretion of adrenocorticotropic hormone (ACTH) takes place. This leads to the stimulation of cortisol release into the blood from the adrenal glands, which are located atop the kidneys. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3860380/)
In normal conditions, levels of cortisol are balanced, and the stress reaction is under control (see in green). However, increased cortisol leads to the inhibition of CRH and ACTH secretion by a negative feedback loop; this situation causes hyperreactivity to stress (see in red). In parallel, the excess of cortisol favors anxiety and depression and affects normal nociceptiv processing.
☑️ Right: Likewise, high levels of cortisol and nociceptive facilitation also lead to functional impairments of specific brain regions, such as the hippocampus, amygdala, medial prefrontal cortex, cingulate gyrus, and thalamus. (https://pubmed.ncbi.nlm.nih.gov/34862336/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3754458/)
All these brain areas activate emotional circuits, and alterations may cause dysfunctional affective symptoms, including anxiety and depression (https://pubmed.ncbi.nlm.nih.gov/27246519/). The dysregulated HPA axis, especially its hyperactivation, favors the impairments observed in the abovementioned brain areas. Moreover, acute and chronic stress activates the HPA axis differently in terms of intensity and duration of stimulation, releasing different levels of glucocorticoids. This may explain the hyperalgesia observed after acute or chronic stress conditions, characterized by increased sensitivity to mechanical stimuli, for example. The transmission of nociceptive information from the periphery to the CNS via Aδ and C fibers crosses the dorsal root ganglia, reaches the spinal cord, the brain stem, and the thalamus, which then project the transmission to different subdivisions of the primary and secondary somatosensory cortex and subcortical structures such as the cingulate gyrus, amygdala, and hippocampus. There is a remarkable overlap of activation of such structures, increasing the response to neuropathic pain and stress, which will result in alterations of emotional circuits, thus causing anxiety and depression.
The descending modulatory system can amplify or decrease a pain experience (https://pubmed.ncbi.nlm.nih.gov/34105694/). Psychological aspects, such as expectations and mood state, also influence the activity of the descending modulatory system (https://pubmed.ncbi.nlm.nih.gov/15082122/, https://pubmed.ncbi.nlm.nih.gov/11839418/) and can be related, for example, to the placebo analgesic effects observed in some studies (https://pubmed.ncbi.nlm.nih.gov/24656247/).This is an important mechanism for endogenous analgesia, and its function is attenuated after nerve injury and neuropathic pain states (https://pubmed.ncbi.nlm.nih.gov/22981090/).
