Does Low Grade Systemic Inflammation Have a Role in Chronic Pain?

Abstract

One of the major clinical manifestations of peripheral neuropathy, either resulting from trauma or diseases, is chronic pain. While it significantly impacts patients’ quality of life, the underlying mechanisms remain elusive, and treatment is not satisfactory. Systemic chronic inflammation (SCI) that we are referring to in this perspective is a state of low-grade, persistent, non-infective inflammation, being found in many physiological and pathological conditions. Distinct from acute inflammation, which is a protective process fighting against intruders, SCI might have harmful effects. It has been associated with many chronic non-communicable diseases. We hypothesize that SCI could be a predisposing and/or precipitating factor in the development of chronic pain, as well as associated comorbidities. We reviewed evidence from human clinical studies indicating the coexistence of SCI with various types of chronic pain. We also collated existing data about the sources of SCI and who could have it, showing that those individuals or patients having SCI usually have higher prevalence of chronic pain and psychological comorbidities. We thus elaborate on the need for further research in the connection between SCI and chronic pain. Several hypotheses have been proposed to explain these complex interactions.

Unbiased proteomic analysis detects painful systemic inflammatory profile in the serum of nerve injured mice

“…The potential of systemic contribution in chronic pain has drawn attention in recent years [74]. Some inflammatory mediators, mainly cytokines/chemokines, have been repeatedly detected in the blood of patients suffering from chronic pain with different pathologies, including injury associated peripheral neuropathy [28; 37; 61]; complex regional pain syndrome (CRPS) [60]; diabetic neuropathy [11]; and also in chronic widespread pain (CWP) patients [20; 62; 65].…”

Burning mouth syndrome as a manifestation of an unbalanced psycho-neuro-immuno-endocrine axis in mentally ill women with intestinal dysbiosis: A literature review

“…The gathered background allows BMS to be proposed as a prevalent oral neuropathy in psychiatric women and linked to an alteration in the psycho-neuro-immuno-endocrine axis in which the intestinal microbiome would be a key player in the pathogenesis of this syndrome. Indeed, studies sustain that intestinal dysbiosis would cause immune deregulation with high levels of pro-inflammatory cytokines [17,35], event that has been observed in murine models of neuropathic pain with intestinal dysbiosis [22]. This change in the immune profile with a predominance of pro-inflammatory cytokines would lead to a state of SCI probably resulting in a central neurogenic alteration (linked to the deficiency of certain neurotransmitters such as dopamine and serotonin, in addition to altered connectivity in brain regions related to the modulation of pain) [11,35,43], and peripheral (linked to a small fiber atrophic process) [11,40].…”

“…Indeed, studies sustain that intestinal dysbiosis would cause immune deregulation with high levels of pro-inflammatory cytokines [17,35], event that has been observed in murine models of neuropathic pain with intestinal dysbiosis [22]. This change in the immune profile with a predominance of pro-inflammatory cytokines would lead to a state of SCI probably resulting in a central neurogenic alteration (linked to the deficiency of certain neurotransmitters such as dopamine and serotonin, in addition to altered connectivity in brain regions related to the modulation of pain) [11,35,43], and peripheral (linked to a small fiber atrophic process) [11,40]. Dopaminergic deficiency has been reported in BMS and anxiety disorder [11,17,43].…”

“…Zhou et al recently presented in their perspective review published in Frontiers in Molecular Neuroscience, clinical evidence to support their hypothesis about the impact of SCI on the genesis of chronic pain, as well as the pathological processes that cause SCI. Regarding the latter, psychiatric disorders such as depression are proposed as a cause of SCI and based on the evidence obtained by Zhou et al, SCI is postulated as a cause of chronic pain given the predominance of mRNA and protein level for pro-inflammatory cytokines such as IL-2; IL-1 and TNF in the serum of patients with chronic neuropathic pain, when compared with patients with non-painful neuropathic pain and healthy subjects [35]. Regarding the pathogenesis of the SCI and chronic pain association, now there are only two hypotheses.…”

“…The second hypothesis proposes that the free nerve endings (nociceptors) and their body (DRG) lacking barriers such as the BBB; blood nerve barrier (BNB) and blood spinal cord barrier (BSCB) are directly exposed to circulating products and other danger signals, generating chronic pain responses. However, according to Zhou et al, it is not yet clear whether this repeated chronic stimulation in the SCI context is sufficient to excite nociceptors or sensory neurons [35].…”