The role of neuroinflammation and neuroimmune activation in persistent pain

DeLeo, Joyce A.; Yezierski, Robert P.

doi:10.1016/s0304-3959(00)00490-5

Cited by 593 publications

(394 citation statements)

References 25 publications

Supporting

Mentioning

383

Contrasting

Unclassified

Order By: Relevance

“…2,3,19 In both the peripheral and central models of neuropathic pain, the elevated levels of TNF-a, IL-1b, and IL-6 mRNA are associated with allodynia and hyperalgesia in response to nerve injury. 2,3,19 Intrathecal injections of IL-6 neutralizing antibody significantly reduce nerve injury-induced mechanical allodynia. 20 Inhibition of proinflammatory cytokines, TNF-a and IL-1b, attenuates painassociated behaviour in a dose-dependent manner in rats with neuropathic pain.…”

Section: Discussionmentioning

confidence: 99%

“…1 A growing body of literature indicates that central neuroimmune and neuroinflammatory activation produces and maintains neuropathic pain after nerve injury. 2,3 The typical pro-inflammatory cytokines tumour necrosis factor (TNF-a), interleukin (IL)-1b, and IL-6 are strongly implicated in the initiation and development of the neuropathic pain after nerve injury. [3][4][5] In contrast, as an antiinflammatory cytokine, IL-10 attenuates the neuropathic pain after nerve injury.…”

Section: Résumémentioning

confidence: 99%

“…2,3 The typical pro-inflammatory cytokines tumour necrosis factor (TNF-a), interleukin (IL)-1b, and IL-6 are strongly implicated in the initiation and development of the neuropathic pain after nerve injury. [3][4][5] In contrast, as an antiinflammatory cytokine, IL-10 attenuates the neuropathic pain after nerve injury. 2,5,6 Nuclear factor-kappa B (NF-jB) is one of the most important transcription factors regulating gene expression of the pro-inflammatory cytokines.…”

Section: Résumémentioning

confidence: 99%

See 2 more Smart Citations

Effects of recombinant human erythropoietin on neuropathic pain and cerebral expressions of cytokines and nuclear factor-kappa B

Jia

Jin

et al. 2009

Can J Anesth/J Can Anesth

View full text Add to dashboard Cite

Purpose The effect of recombinant human erythropoietin (rhEPO) on neuropathic pain remains unclear. This study aimed to determine the effects of preemptive administration of rhEPO on the behavioural changes and neuroinflammatory responses in a rat model of neuropathic pain. Methods Fifty rats were randomly allocated into five groups, sham-operation treated with saline and L5 spinal nerve transection treated with different doses of rhEPO (0 [saline], 1000, 3000, or 5000 U Á kg -1 , respectively). The rats were intraperitoneally treated from 1 day before surgery to post-surgery day 7. The mechanical (paw pressure thresholds, PPT) and thermal thresholds (paw withdrawal latencies, PWL) were measured on post-surgery days 1, 3, and 7. The contralateral brain was obtained on post-surgery day 7 to determine the expressions of tumour necrosis factor (TNF-a), interleukin (IL)-1b, IL-6, L-10, and nuclear factor-kappa B (NF-jB) activity. Results There were significant decreases in PPT and PWL after L5 spinal nerve transection (P \ 0

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Résumémentioning

confidence: 99%

Section: Résumémentioning

confidence: 99%

See 1 more Smart Citation

Effects of recombinant human erythropoietin on neuropathic pain and cerebral expressions of cytokines and nuclear factor-kappa B

Jia

Jin

et al. 2009

Can J Anesth/J Can Anesth

View full text Add to dashboard Cite

show abstract

“…In contrast to inflammatory pain, treatments for neuropathic pain is lacking, and therefore is a requirement to understand its molecular pathogenesis [83]. It is now thought that the basis of neuropathic pain requires immune activation in the CNS, where the production of chemokines and cytokines triggers the expression of pain mediators such as glutamate and NO [80,[84][85][86]. Critically proinflammtory cytokines such as TNF, IL-1 and IL-6 have not been associated with the generation of normal non pathological pain, yet these mediators are all associated with conditions where pain is exadurated [78].…”

Section: Of 62mentioning

confidence: 99%

Evaluating the role of Toll-like receptors in diseases of the central nervous system

Carty

Bowie

2011

Biochemical Pharmacology

134

View full text Add to dashboard Cite

A key part of the innate immune system is a network of pattern recognition receptors (PRRs) and their associated intracellular signalling pathways. Toll-like receptors (TLRs) are one such group of PRRs that detect pathogen associated molecular patterns (PAMPs). Activation of the TLRs with their respective agonists results in the activation of intracellular signalling pathways leading to the expression of proinflammatory mediators and anti-microbial effector molecules. Activation of the innate immune system through TLRs also triggers the adaptive immune response, resulting in a comprehensive immune program to eradicate invading pathogens. It is now known that immune surveillance and inflammatory responses occur in the central nervous system (CNS). Furthermore it is becoming increasingly clear that TLRs have a role in such CNS responses andare also implicated in the pathogenesis of a number of conditions in the CNS, such as Alzheimer's, stroke and multiple sclerosis. This is likely due to the generation of endogenous TLR agonists in these conditions which amplifies a detrimental neurotoxic inflammatory response. However TLRs in some situations can be neuroprotective, if triggered in a favourable context. This review aims to examine the recent literature on TLRs in the CNS thus demonstrating their importance in a range of infectious and non-infectious diseases of the brain.

show abstract

“…In particular, evidence is accruing that adenosine triphosphate (ATP), acting via P2 purinergic receptors, is involved in pain hypersensitivity associated with neuropathic pain and peripheral inflammation [12,23,24,39]. ATP released from damaged and/or inflamed tissue directly modulates microglial functioning, and microglia in turn release a myriad of cytokines, chemokines, and neurotrophic factors that have a profound effect on neuronal function [15,21,36,71,82,86]. In vivo imaging studies show that upon traumatic injury microglia rapidly extend processes by an ATP-dependent mechanism and converge on the site of injury [19,32,45,53].…”

Section: Introductionmentioning

confidence: 99%

P2X4 purinoceptor signaling in chronic pain

Trang

Salter

2012

Purinergic Signalling

View full text Add to dashboard Cite

ATP, acting via P2 purinergic receptors, is a known mediator of inflammatory and neuropathic pain. There is increasing evidence that the ATP-gated P2X4 receptor (P2X4R) subtype is a locus through which activity of spinal microglia and peripheral macrophages instigate pain hypersensitivity caused by inflammation or by injury to a peripheral nerve. The present article highlights the recent advances in our understanding of microglia-neuron interactions in neuropathic pain by focusing on the signaling and regulation of the P2X4R. We will also develop a framework for understanding converging lines of evidence for involvement of P2X4Rs expressed on macrophages in peripheral inflammatory pain.

show abstract

The role of neuroinflammation and neuroimmune activation in persistent pain

Cited by 593 publications

References 25 publications

Effects of recombinant human erythropoietin on neuropathic pain and cerebral expressions of cytokines and nuclear factor-kappa B

Effects of recombinant human erythropoietin on neuropathic pain and cerebral expressions of cytokines and nuclear factor-kappa B

Evaluating the role of Toll-like receptors in diseases of the central nervous system

P2X4 purinoceptor signaling in chronic pain

Contact Info

Product

Resources

About