Neuroinflammation, Pain and Depression: An Overview of the Main Findings

Abstract

Chronic pain is a serious public health problem with a strong affective-motivational component that makes it difficult to treat. Most patients with chronic pain suffer from severe depression; hence, both conditions coexist and exacerbate one another. Brain inflammatory mediators are critical for maintaining depression-pain syndrome and could be substrates for it. The goal of our paper was to review clinical and preclinical findings to identify the neuroinflammatory profile associated with the cooccurrence of pain and depression. In addition, we aimed to explore the regulatory effect of neuronal reorganization on the inflammatory response in pain and depression. We conducted a quantitative review supplemented by manual screening. Our results revealed inflammatory signatures in different preclinical models and clinical articles regarding depression-pain syndrome. We also identified that improvements in depressive symptoms and amelioration of pain can be modulated through direct targeting of inflammatory mediators, such as cytokines and molecular inhibitors of the inflammatory cascade. Additionally, therapeutic targets that improve and regulate the synaptic environment and its neurotransmitters may act as anti-inflammatory compounds, reducing local damage-associated molecular patterns and inhibiting the activation of immune and glial cells. Taken together, our data will help to better elucidate the neuroinflammatory profile in pain and depression and may help to identify pharmacological targets for effective management of depression-pain syndrome.

TRPV1 Responses in the Cerebellum Lobules VI, VII, VIII Using Electroacupuncture Treatment for Chronic Pain and Depression Comorbidity in a Murine Model

“…GABAAα1 signaling mechanisms have been revealed by structural pharmacology [ 48 ] and have been evidenced for their large operative role in both pain and depression pathologies [ 49 ]. Evidence suggests that early-stage neuroinflammation, potentially caused by acute injury, inhibits GABAAα1 expression through astrocyte activation, which subsequently downregulates the BDNF-TrkB signal pathway and results in an impairment of neurogenesis, thus affecting depression-like symptoms concurrently associated with chronic pain comorbidities [ 50 ].…”

Pain in Covid Era

“…The risks of harm from under treatment can be aggravated further by inadequate treatment ( Eccleston et al, 2020 ). Despite the fact that pharmacological therapies for pain management and related syndromes tend to be ineffective, negatively affecting the quality of life of individuals ( Shamji et al, 2017 ; Campos et al, 2020 ), opioids and non-steroidal anti-inflammatory drugs are commonly used in the treatment of acute and chronic pain, even considering their adverse effects, tolerance and potential for addiction ( Busse et al, 2018 ; Szok et al, 2019 ; Campos et al, 2020 ). Thus, the impact of the cessation of pain treatment caused by the COVID19 pandemic can lead to several unintended consequences, such as increased pain, reduced function, increased reliance on opioid medications and potential increased morbidity ( Deer et al, 2020 ; El-Tallawy et al, 2020 ).…”

Quantitative Sensory Testing to Predict Postoperative Pain

“…Multiple factors influence the perception of pain, such as genetic determinants, neurological diseases affecting the central or peripheral nervous system, inflammatory modulation of tissue, and the presence of inflammatory mediators, as well as experience of pain, i.e., peripheral sensitization of pain possibly leading to central modulation of pain pathways [ 2 , 19 – 25 ]. Also, psychological factors such as resilience, depression, pain catastrophizing, mood, positive or negative emotions, and stress affect the sensation of pain [ 26 – 29 ].…”