THIS ARTICLE HAS BEEN RETRACTED: Toll‐like receptor 3 contributes to spinal glial activation and tactile allodynia after nerve injury

Obata, Koichi; Katsura, Hirokazu; Miyoshi, Kan; Kondo, Takashi; Yamanaka, Hiroki; Kobayashi, Kimiko; Dai, Yi; Fukuoka, Tetsuo; Akira, Shizuo; Noguchi, Koichi

doi:10.1111/j.1471-4159.2008.05353.x

Cited by 70 publications

(69 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data indicate that TLR3 is critical for the development of neuropathic pain [83]. Since TLR3 binds mRNA released from necrotic cells it has been suggested that this may be the mechanism responsible for the TLR3 role in neuropathic pain [79].…”

mentioning

confidence: 83%

“…This type of pain in not protective and is itself regarded as a pathological condition [82]. 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].…”

Section: Of 62mentioning

confidence: 99%

“…Interestingly intrathecal administration of the TLR3 agonist poly(I:C) produced many of the features characteristic of nerve injury [83]. In addition TLR3 knockout mice failed to develop tactile allodynia (painful response to non painful stimuli) after nerve injury or poly(I:C) injection.…”

mentioning

confidence: 99%

“…Since TLR3 binds mRNA released from necrotic cells it has been suggested that this may be the mechanism responsible for the TLR3 role in neuropathic pain [79]. This indicates that blockade of TLR3 in spinal cord glial cells may potentially be beneficial in the treatment of neuropathic pain [83].…”

mentioning

confidence: 99%

See 3 more Smart Citations

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

mentioning

confidence: 83%

Section: Of 62mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

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

show abstract

“…Mice lacking either toll‐like receptor 2, 3 or 4 show impaired microglial activation in the dorsal horn after PNI42, 43, 44.…”

Section: Microglia In the Spinal Cord In Pni And Diabetic Animalsmentioning

confidence: 99%

Microglia in the spinal cord and neuropathic pain

Tsuda

2015

J of Diabetes Invest

208

147

View full text Add to dashboard Cite

In contrast to physiological pain, pathological pain is not dependent on the presence of tissue‐damaging stimuli. One type of pathological pain – neuropathic pain – is often a consequence of nerve injury or of diseases such as diabetes. Neuropathic pain can be agonizing, can persist over long periods and is often resistant to known painkillers. A growing body of evidence shows that many pathological processes within the central nervous system are mediated by complex interactions between neurons and glial cells. In the case of painful peripheral neuropathy, spinal microglia react and undergo a series of changes that directly influence the establishment of neuropathic pain states. After nerve damage, purinergic P2X4 receptors (non‐selective cation channels activated by extracellular adenosine triphosphate) are upregulated in spinal microglia in a manner that depends on the transcription factors interferon regulatory factor 8 and 5, both of which are expressed in microglia after peripheral nerve injury. P2X4 receptor expression on the cell surface of microglia is also regulated at the post‐translational level by signaling from CC chemokine receptor chemotactic cytokine receptor 2. Furthermore, spinal microglia in response to extracellular stimuli results in signal transduction through intracellular signaling cascades, such as mitogen‐activated protein kinases, p38 and extracellular signal‐regulated protein kinase. Importantly, inhibiting the function or expression of these microglial molecules suppresses the aberrant excitability of dorsal horn neurons and neuropathic pain. These findings show that spinal microglia are a central player in mechanisms for neuropathic pain, and might be a potential target for treating the chronic pain state.

show abstract