Peripheral Nervous System Manifestations of Infectious Diseases

Brizzi, Kate; Lyons, Jennifer L.

doi:10.1177/1941874414535215

Cited by 52 publications

(55 citation statements)

References 78 publications

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“…Among the earliest symptoms of viral infection are aches and pain, effects that are usually body-wide suggest a systemic factor as a cause. While viral infections often cause pain that persists during the course of the ensuing illness, some viral infections, and sustained antiviral responses, can cause neuropathies leading to chronic pain (Brizzi and Lyons, 2014; Rodriguez et al, 2019). For instance, HIV and herpes viruses cause painful neuropathies that can last for decades (Hadley et al, 2016; Aziz-Donnelly and Harrison, 2017).…”

Section: Introductionmentioning

confidence: 99%

Type I interferons act directly on nociceptors to produce pain sensitization: Implications for viral infection-induced pain

Barragán-Iglesias¹,

Franco-Enzástiga

Jeevakumar³

et al. 2019

Preprint

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ABSTRACTOne of the first signs of viral infection is body-wide aches and pain. While this type of pain usually subsides, at the extreme, viral infections can induce painful neuropathies that can last for decades. Neither of these types of pain sensitization are well understood. A key part of the response to viral infection is production of interferons (IFNs), which then activate their specific receptors (IFNRs) resulting in downstream activation of cellular signaling and a variety of physiological responses. We sought to understand how type I IFNs (IFN-α and IFN-β) might act directly on nociceptors in the dorsal root ganglion (DRG) to cause pain sensitization. We demonstrate that type I IFNRs are expressed in small/medium DRG neurons and that their activation produces neuronal hyper-excitability and mechanical pain in mice. Type I IFNs stimulate JAK/STAT signaling in DRG neurons but this does not apparently result in PKR-eIF2α activation that normally induces an anti-viral response by limiting mRNA translation. Rather, type I interferons stimulate MNK-mediated eIF4E phosphorylation in DRG neurons to promote pain hypersensitivity. Endogenous release of type I IFNs with the double stranded RNA mimetic poly(I:C) likewise produces pain hypersensitivity that is blunted in mice lacking MNK-eIF4E signaling. Our findings reveal mechanisms through which type I IFNs cause nociceptor sensitization with implications for understanding how viral infections promote pain and can lead to neuropathies.SIGNIFICANCE STATEMENTIt is increasingly understood that pathogens interact with nociceptors to alert organisms to infection as well as to mount early host defenses. While specific mechanisms have been discovered for diverse bacteria and fungal pathogens, mechanisms engaged by viruses have remained elusive. Here we show that type 1 interferons, one of the first mediators produced by viral infection, act directly on nociceptors to produce pain sensitization. Type I interferons act via a specific signaling pathway (MNK-eIF4E signaling) that is known to produce nociceptor sensitization in inflammatory and neuropathic pain conditions. Our work reveals a mechanism through which viral infections cause heightened pain sensitivity

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Section: Introductionmentioning

confidence: 99%

Type I interferons act directly on nociceptors to produce pain sensitization: Implications for viral infection-induced pain

Barragán-Iglesias¹,

Franco-Enzástiga

Jeevakumar³

et al. 2019

Preprint

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“…While comorbidities with peripheral neuropathy has been largely investigated (Sachedina and Toth, ), the coexistence of symptomatologies of PNI and other diseases is not well known. Herpes simplex virus type 1 and 2 (HSV1, HSV2) are well‐known neurotropic viruses residing in neural ganglia, and reactivation of the dormant virus can be under a range of both CNS and PNS diseases (Brizzi and Lyons, ). In their report in this Thematic Papers issue, Gumenyuk et al report that HSV1 infection has a negative impact on nerve lesion, and the muscle metabolism is not recovered even after acyclovir administration (Gumenyuk et al, ).…”

Section: Other Diseases Other Therapiesmentioning

confidence: 99%

Advances in the Ongoing Battle against the Consequences of Peripheral Nerve Injuries

Trejo

2018

The Anatomical Record

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“…In 90.2% of stomach cancer cases, the DNA of Epstein-Barr virus (EBV) was detected; however, 11% of them have EBVencoded small RNAs (EBERs) [15][16][17]. Herpes viridea is classified as double-stranded DNA family viruses and with different mechanisms is able to escape from immune system [18]. Varicella zoster virus (VZV), Herpes simplex virus type 1 (HSV-1), type 2 (HSV-2) and cytomegalovirus (CMV) are the most known members of this virus family, and have a potential to infect and establish persistent infections in the host.…”

Section: Introductionmentioning

confidence: 99%

Prevalence of herpes simplex, varicella zoster and Cytomegalovirus in tumorous and adjacent tissues of patients, suffering from colorectal cancer in Iran

et al. 2019

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Background: Colorectal cancer (CRC) can be considered as a result of multiple risks factors, and the significant role of infectious ones, especially viral diseases could not be underestimated. Despite endorsed attempts to identify the accelerating effects of different herpes viridea, such as HSV-1, HSV2, VZV and CMV on the deterioration of different kinds of malignancy, the relationship between these viruses and CRC have not successfully been understood. Taking advantages of these facts, we assessed the role of these viruses on CRC progression. Methods: In this case-control study, 88 cancerous specimens and 70 their adjacent paraffin-embedded tissues from Modares Hospital between 2011 and 2019 were collected. We extracted the DNA of each tissue and investigated the presence of HSV-1, HSV2, VZV and CMV. Results: Our data indicated the presence of HSV-1 DNA in the three control samples; however, we could not find an obvious relationship between HSV2, VZV, CMV infection and this type of cancer. The presence of HSV-1 DNA in control tissues introduced HSV-1 as a probable factor for the killing of colorectal cancer cells. Conclusions: we supposed that HSV-1 can function as an inhibitor of colon cancer progresion, but it is required to studied more in order to find the role of this virus on CRC.

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Peripheral Nervous System Manifestations of Infectious Diseases

Cited by 52 publications

References 78 publications

Type I interferons act directly on nociceptors to produce pain sensitization: Implications for viral infection-induced pain

Type I interferons act directly on nociceptors to produce pain sensitization: Implications for viral infection-induced pain

Advances in the Ongoing Battle against the Consequences of Peripheral Nerve Injuries

Prevalence of herpes simplex, varicella zoster and Cytomegalovirus in tumorous and adjacent tissues of patients, suffering from colorectal cancer in Iran

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