Cell death in vasculitic neuropathy

Heuss, Dieter; Probst‐Cousin, Stefan; Kayser, Corinna; Neundörfer, B.

doi:10.1002/1097-4598(200007)23:7<999::aid-mus1>3.0.co;2-i

Cited by 18 publications

(6 citation statements)

References 32 publications

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“…The specific changes in sensory neurons in patients with peripheral neuropathies that mediate pain, has remained elusive. Given that many forms of nerve injury can also produce death of sensory neurons (Miller, 1995; Gill & Windebank, 1998; Heuss et al ., 2000; McDonald & Windebank, 2002; Peltier & Russell, 2002; Groves et al ., 2003; Ekshyyan & Aw, 2004), we tested the hypothesis that activation of cell death signalling pathways, the signature event for which is activation of both proximal/activator and distal/effector caspases (Degterev et al ., 2003), has a role in neuropathic pain. Models of three painful peripheral neuropathies with different pathophysiology were evaluated: AIDS‐therapy neuropathy (Joseph et al ., 2004) induced by nucleoside reverse transcriptase inhibitors (NRTIs), thought to be a result of NRTI‐induced mitochondrial damage (Dalakas, 2001; Dalakas et al ., 2001); vincristine‐chemotherapy neuropathy (Aley et al ., 1996; Tanner et al ., 1998b), thought to be a result of cytoskeleton disruption (Tanner et al ., 1998a); and diabetic neuropathy, thought to be from hyperglycemia‐induced changes in multiple sensory neuron mechanisms (Obrosova, 2002; Simmons & Feldman, 2002; van Dam, 2002).…”

Section: Discussionmentioning

confidence: 99%

Caspase signalling in neuropathic and inflammatory pain in the rat

Joseph

Levine

2004

Eur J of Neuroscience

192

141

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Whereas small-fibre sensory neuropathies might ultimately lead to cell death and loss of sensation, they first progress through a phase, which might last for years, characterized by the presence of analgesia-resistant neuropathic dysesthesias and pain. Much previous research has addressed these two phases as separate phenomena mediated by presumably discrete biochemical mechanisms. We hypothesized that activity in signalling pathways that ultimately lead to apoptosis plays a critical role in the generation of neuropathic pain, before death of sensory neurons becomes apparent. We have tested the hypothesis that activator and effector caspases, defining components of programmed cell death (apoptosis) signalling pathways, also contribute to pain-related behaviour in animals with small-fibre peripheral neuropathies and that the death receptor ligand, tumour necrosis factor-alpha, and its downstream second messenger, ceramide, also produce pain-related behaviour via this mechanism. In two models of painful peripheral neuropathy, HIV/AIDS therapy (induced by the nucleoside reverse transcriptase inhibitor, dideoxycytidine), and cancer chemotherapy (induced by vincristine) peripheral neuropathy, and for pain-related behaviour induced by tumour necrosis factor-alpha and its second messenger, ceramide, inhibition of both activator (1, 2, 8 and 9) and effector (3) caspases attenuates neuropathic pain-related behaviour, although has no effect in streptozotocin-diabetic neuropathy and control rats. We conclude that during a latent phase, before apoptotic cell death is manifest, the caspase signalling pathway can contribute to pain in small-fibre peripheral neuropathies, and that inflammatory/immune mediators also activate these pathways. This suggests that these pathways are potential targets for novel pharmacological agents for the treatment of inflammatory as well as neuropathic pain.

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Section: Discussionmentioning

confidence: 99%

Caspase signalling in neuropathic and inflammatory pain in the rat

Joseph

Levine

2004

Eur J of Neuroscience

192

141

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“…In vasculitic neuropathy, the characteristic perivascular infiltrate expresses GrB and GrB-positive cells are significantly upregulated. 201 In sensory perineuritis, GrB-expressing infiltrates were detected and T cells are believed to contribute to perineural cell apoptosis. 202 During cerebral ischemia, in a rat model of ischemic stroke, GrB secreted from CTLs and NK cells results in the breakdown of Hsp-70 and AIF translocation from the mitochondria to the nucleus, ultimately resulting in apoptosis of brain cells.…”

Section: Neurological Disordersmentioning

confidence: 93%

Intracellular versus extracellular granzyme B in immunity and disease: challenging the dogma

Boivin

Cooper

Hiebert

et al. 2009

Laboratory Investigation

256

290

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“…Some forms of vasculitis are thought to result from viral infections, including HIV-1 and hepatitis C (85). While cytotoxic T lymphocytes have been proposed as the mediator of some forms of vasculitis (102), several studies fail to find evidence of T-lymphocyte involvement (24,110). Other forms of vasculitis may derive from the expression of autoantibodies.…”

Section: Clinical Correlation: Vasculitic Neuropathymentioning

confidence: 99%

“…VN typically occurs at multiple sites throughout the body, scattered randomly across nerves (i.e., an asymmetrical polyneuropathy) (102,337). It is caused primarily as a result of the ischemia that follows blood vessel injury, coagulation, and necrosis (110). VN is characterized by acute pain as well as edema in the affected portion of the limb.…”

Section: C) Evidence For Ischemia-induced Nerve and Immune Changesmentioning

confidence: 99%

Beyond Neurons: Evidence That Immune and Glial Cells Contribute to Pathological Pain States

Watkins

Maier

2002

Physiological Reviews

653

433

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Chronic pain can occur after peripheral nerve injury, infection, or inflammation. Under such neuropathic pain conditions, sensory processing in the affected body region becomes grossly abnormal. Despite decades of research, currently available drugs largely fail to control such pain. This review explores the possibility that the reason for this failure lies in the fact that such drugs were designed to target neurons rather than immune or glial cells. It describes how immune cells are a natural and inextricable part of skin, peripheral nerves, dorsal root ganglia, and spinal cord. It then examines how immune and glial activation may participate in the etiology and symptomatology of diverse pathological pain states in both humans and laboratory animals. Of the variety of substances released by activated immune and glial cells, proinflammatory cytokines (tumor necrosis factor, interleukin-1, interleukin-6) appear to be of special importance in the creation of peripheral nerve and neuronal hyperexcitability. Although this review focuses on immune modulation of pain, the implications are pervasive. Indeed, all nerves and neurons regardless of modality or function are likely affected by immune and glial activation in the ways described for pain.

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Cell death in vasculitic neuropathy

Cited by 18 publications

References 32 publications

Caspase signalling in neuropathic and inflammatory pain in the rat

Caspase signalling in neuropathic and inflammatory pain in the rat

Intracellular versus extracellular granzyme B in immunity and disease: challenging the dogma

Beyond Neurons: Evidence That Immune and Glial Cells Contribute to Pathological Pain States

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