Immune system involvement in specific pain conditions

Totsch, Stacie K.; Sorge, Robert E.

doi:10.1177/1744806917724559

Cited by 101 publications

(98 citation statements)

References 175 publications

(179 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Within 3 days of injury, macrophages and neutrophils are recruited to the site and secrete cytokines which aid helper T cells and B cells as well as sensitize peripheral nociceptors (11). These inflammatory mediators include pro-inflammatory cytokines like TNF-α, IL-1β, IL-6, and IL-17, nerve growth factor (NGF), serotonin, histamine, and prostaglandins like prostaglandin E2 (PGE2) (12).…”

Section: Overview Of Immune Contributions To Pathological Pain Periphmentioning

confidence: 99%

Cytokines in Pain: Harnessing Endogenous Anti-Inflammatory Signaling for Improved Pain Management

2019

View full text Add to dashboard Cite

Current pain therapeutics offer inadequate relief to patients with chronic pain. A growing literature supports that pro-inflammatory cytokine signaling between immune, glial, and neural cells is integral to the development of pathological pain. Modulation of these communications may hold the key to improved pain management. In this review we first offer an overview of the relationships between pro-inflammatory cytokine and chemokine signaling and pathological pain, with a focus on the actions of cytokines and chemokines in communication between glia (astrocytes and microglia), immune cells (macrophages and T cells), and neurons. These interactions will be discussed in relation to both peripheral and central nervous system locations. Several novel non-neuronal drug targets for controlling pain are emerging as highly promising, including non-viral IL-10 gene therapy, which offer the potential for substantial pain relief through localized modulation of targeted cytokine pathways. Preclinical investigation of the mechanisms underlying the success of IL-10 gene therapy revealed the unexpected discovery of the powerful anti-nociceptive anti-inflammatory properties of D-mannose, an adjuvant in the non-viral gene therapeutic formulation. This review will include gene therapeutic approaches showing the most promise in controlling pro-inflammatory signaling via increased expression of anti-inflammatory cytokines like interleukin-10 (IL-10) or IL-4, or by directly limiting the bioavailability of specific pro-inflammatory cytokines, as with tumor necrosis factor (TNF) by the TNF soluble receptor (TNFSR). Approaches that increase endogenous anti-inflammatory signaling may offer additional opportunities for pain therapeutic development in patients not candidates for gene therapy. Promising novel avenues discussed here include the disruption of lymphocyte function-associated antigen (LFA-1) activity, antagonism at the cannabinoid 2 receptor (CB2R), and toll-like receptor 4 (TLR4) antagonism. Given the partial efficacy of current drugs, new strategies to manipulate neuroimmune and cytokine interactions hold considerable promise.

show abstract

Section: Overview Of Immune Contributions To Pathological Pain Periphmentioning

confidence: 99%

Cytokines in Pain: Harnessing Endogenous Anti-Inflammatory Signaling for Improved Pain Management

2019

View full text Add to dashboard Cite

show abstract

“…In fibromyalgia, the hypothalamic-pituitary-adrenal axis (HPA) is considered to play a role in the establishment of central sensitization [13,14].…”

Section: Introductionmentioning

confidence: 99%

“…Patients with centralized pain syndromes can display hyper-or hypocortisolism and altered downstream signaling from the HPA axis. This includes increased infiltration of mast cells that also express receptors for CRH [13]. Release of granule from activated mast cells can lead to sensitization of peripheral and central nociceptors and the increase of pro-inflammatory cytokines [8][9][10]15].…”

Section: Introductionmentioning

confidence: 99%

T Cell Subpopulations in the Physiopathology of Fibromyalgia: Evidence and Perspectives

Banfi

Diani

Pigatto

et al. 2020

IJMS

View full text Add to dashboard Cite

Fibromyalgia is one of the most important "rheumatic" disorders, after osteoarthritis. The etiology of the disease is still not clear. At the moment, the most defined pathological mechanism is the alteration of central pain pathways, and emotional conditions can trigger or worsen symptoms. Increasing evidence supports the role of mast cells in maintaining pain conditions such as musculoskeletal pain and central sensitization. Importantly, mast cells can mediate microglia activation through the production of proinflammatory cytokines such as IL-1β, IL-6, and TNFα. In addition, levels of chemokines and proinflammatory cytokines are enhanced in serum and could contribute to inflammation at systemic level. Despite the well-characterized relationship between the nervous system and inflammation, the mechanism that links the different pathological features of fibromyalgia, including stress-related manifestations, central sensitization, and dysregulation of the innate and adaptive immune responses is largely unknown. This review aims to provide an overview of the current understanding of the role of adaptive immune cells, in particular T cells, in the physiopathology of fibromyalgia. It also aims at linking the latest advances emerging from basic science to envisage new perspectives to explain the role of T cells in interconnecting the psychological, neurological, and inflammatory symptoms of fibromyalgia.

show abstract

“…Skin fissures also trigger inflammatory cell recruitment. Immune cells represent a driving force behind inflammatory pain . This is, in part, because cytokines and other molecules released by these immune cells can enhance sensitivity to painful stimuli .…”

Section: Multiple Candidate Structural and Cellular Contributors To Pmentioning

confidence: 99%

“…Immune cells represent a driving force behind inflammatory pain. 38 This is, in part, because cytokines and other molecules released by these immune cells can enhance sensitivity to painful stimuli. 39 It is also conceivable that mutations causing PPK might directly influence immune cell functions.…”

Section: Keratinocytesmentioning

confidence: 99%

Pain mechanisms in hereditary palmoplantar keratodermas

Weinberg

Polydefkis

2019

Br J Dermatol

View full text Add to dashboard Cite

Summary Background Palmoplantar keratodermas (PPKs) are a heterogeneous group of skin disorders characterized by thickening of the epidermis on the palms of the hands and soles of the feet. Individuals with PPKs report varying degrees of palmoplantar pain that can severely affect quality of life. Objectives To provide an overview of the scope of pain in hereditary PPKs and highlight candidate mechanisms underlying this pain. Methods In this review, we discuss several forms of hereditary PPKs, with a focus on the incidence, nature, candidate underlying mechanisms and treatment of pain in these conditions. We also synthesize this information with current understanding of the mechanisms contributing to pathological pain in other conditions. Results Pain is a major problem for many, but not all individuals with hereditary PPK. This pain remains poorly understood, inconsistently reported and inadequately treated. The heterogeneity of pain prevalence and presentations across the many forms of PPK suggests that there may exist corresponding heterogeneity in the cellular and molecular mechanisms that drive and shape PPK‐associated pain. Some candidate mechanisms include structural (e.g. fissures and blisters), infectious and immune/inflammatory processes. However, a growing body of evidence also supports the occurrence of localized neuropathic alterations in the affected skin of individuals with PPK, which might contribute to their pain. Conclusions Greater understanding of these diverse mechanisms may provide a rational basis for the development of improved and targeted approaches to prevention and treatment of pain in individuals with PPK. What's already known about this topic? Pain is a prominent symptom in hereditary palmoplantar keratodermas (PPKs). Pain in patients with PPK can be difficult to treat. Pain mechanisms in PPKs are poorly understood. What does this study add? This study defines multiple potential sources of pain in PPK, including both structural lesions (fissures, blisters) and specific cell types. This review highlights the variability of pain among several forms of hereditary PPK. This study provides mechanistic insights into how neuropathic and inflammatory mechanisms might contribute to pain in some forms of PPK.

show abstract

Immune system involvement in specific pain conditions

Cited by 101 publications

References 175 publications

Cytokines in Pain: Harnessing Endogenous Anti-Inflammatory Signaling for Improved Pain Management

Cytokines in Pain: Harnessing Endogenous Anti-Inflammatory Signaling for Improved Pain Management

T Cell Subpopulations in the Physiopathology of Fibromyalgia: Evidence and Perspectives

Pain mechanisms in hereditary palmoplantar keratodermas

Contact Info

Product

Resources

About