Distal sensory polyneuropathy in HIV-positive patients in the HAART era: an entity underestimated by clinical examination

Skopelitis, Elias; Kokotis, Panagiotis; Kontos, Athanasios; Panayiotakopoulos, George; Konstantinou, Klio; Kordossis, T.; Karandreas, Nikolaos

doi:10.1258/095646206777689062

Cited by 35 publications

(34 citation statements)

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“…Intriguingly, the symptoms of this syndrome are clinically indistinguishable from those of HIV-1-induced DSP, including a burning sensation in the hands and feet and hypersensitivity to pain (92,98,99). The fact that the two syndromes are usually seen in association with one another makes diagnosis more difficult.…”

Section: Chemokines Glia and Chronic Painmentioning

confidence: 99%

“…This has particular relevance for the present discussion because the cellular receptors for gp120, the HIV-1 coat protein, are the CXCR4 and CCR5 chemokine receptors. One example of an HIV-1-associated pain syndrome is distal symmetrical polyneuropathy (DSP), which affects as many as one third of all HIV-1-infected individuals (92). This painful sensory neuropathy frequently begins with paresthesias in the fingers and toes progressing over weeks to months, followed by the development of pain, often of a burning and lancinating nature, which can make walking very difficult.…”

Section: Chemokines Glia and Chronic Painmentioning

confidence: 99%

See 1 more Smart Citation

Chemokines and the pathophysiology of neuropathic pain

White

Jung²,

Miller

2007

Proc. Natl. Acad. Sci. U.S.A.

324

266

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Chemokines and chemokine receptors are widely expressed by cells of the immune and nervous systems. This review focuses on our current knowledge concerning the role of chemokines in the pathophysiology of chronic pain syndromes. Injury-or disease-induced changes in the expression of diverse chemokines and their receptors have been demonstrated in the neural and nonneural elements of pain pathways. Under these circumstances, chemokines have been shown to modulate the electrical activity of neurons by multiple regulatory pathways including increases in neurotransmitter release through Ca-dependent mechanisms and transactivation of transient receptor channels. Either of these mechanisms alone, or in combination, may contribute to sustained excitability of primary afferent and secondary neurons within spinal pain pathways. Another manner in which chemokines may influence sustained neuronal excitability may be their ability to function as excitatory neurotransmitters within the peripheral and central nervous system. As is the case for traditional neurotransmitters, injury-induced up-regulated chemokines are found within synaptic vesicles. Chemokines released after depolarization of the cell membrane can then act on other chemokine receptor-bearing neurons, glia, or immune cells. Because up-regulation of chemokines and their receptors may be one of the mechanisms that directly or indirectly contribute to the development and maintenance of chronic pain, these molecules may then represent novel targets for therapeutic intervention in chronic pain states. In his landmark treatise Sir Charles Scott Sherrington proposed the concept that pain is the evolved response to a potentially harmful, noxious stimulus (1). An example would be placing your hand on a hot iron and the resulting sensation of pain, which produces almost immediate withdrawal, thereby preventing tissue damage. This conscious perception of pain is the result of activity in a set of well defined neural pathways that start with the primary afferent neurons. These pseudounipolar neurons are responsible for the transmission of pain (''nociceptors'') and have unmyelinated or lightly myelinated axons. The cell bodies of nociceptors are found in the dorsal root ganglia (DRG). Nociceptors have both a peripheral connection that innervates potentially diseased or traumatized nerves, muscles, tendons, organs, and epithelia, and a centrally projecting axon that enters the central nervous system. This central axon conveys ''nociceptive'' information to second-order neurons in the dorsal horn of the spinal cord. Neural connections from the dorsal horn to the thalamus, and from there to the cortex, relay this noxious information to higher centers of conscious experience (Fig. 1). The central axons of primary afferent nociceptive neurons also provide information to polysynaptic spinal cord interneurons, which are essential for the initiation of the nociceptive withdrawal reflex. These neurons trigger motor reflexes that are important in the avoidance of potentially harmful ...

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Section: Chemokines Glia and Chronic Painmentioning

confidence: 99%

Section: Chemokines Glia and Chronic Painmentioning

confidence: 99%

Chemokines and the pathophysiology of neuropathic pain

White

Jung²,

Miller

2007

Proc. Natl. Acad. Sci. U.S.A.

324

266

View full text Add to dashboard Cite

show abstract

“…11 It is well established that DSP continues to be a prevalent neurologic complication associated with HIV infection in the HAART era, occurring in 36-62% of subjects infected with HIV. [1][2][3][4] Little is known about the incidence of DSP in the era of HAART. Lichtenstein et al 13 reported an incidence of five cases per 100 person-years from the HIV Outpatient Study (HOPS).…”

Section: Nakamoto Et Almentioning

confidence: 99%

“…1 Nonetheless, HIV-associated distal sensory neuropathy (DSP) continues to be a common neurologic complication seen in HIV-seropositive individuals. [2][3][4] Patients usually present with the gradual onset of distal sensory symptoms in the feet, including numbness, paresthesias, or painful dysesthesias. 5 The painful dysesthesias can be severe enough to limit activities of daily living.…”

mentioning

confidence: 99%

Incident Neuropathy in HIV-Infected Patients on HAART

Nakamoto

McMurtray

Davis

et al. 2010

AIDS Research and Human Retroviruses

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We determined the incidence of and risk factors for distal sensory polyneuropathy (DSP) in individuals on HAART. Sixty-one HIV-positive subjects on HAART for at least 6 months and neuropathy free were retrospectively selected. The study included subjects who had previously tolerated d-drugs without developing DSP. Neuropathy incidence over 4 years was calculated. Cox proportional hazards models were used to determine risk factors associated with incident DSP. Nineteen subjects developed DSP over a mean follow-up of 2.4 years. Subjects never treated with a d-drug developed DSP at a rate of 21 cases per 100 person-years (95% CI, 8.9-33.7). Subjects with a history of d-drug treatment but not on a d-drug at enrollment developed DSP at a rate of 17 cases per 100 person-years (95% CI, 2.1-31.8). Those on d-drug treatment developed DSP at a rate of 25 cases per 100 person-years (95% CI, 8.7-41.6). Multivariable analysis identified age [hazard ratio (HR) ¼ 1.09; p < 0.01] and low CD4 þ nadir [hazard ratio (HR) ¼ 0.79; p ¼ 0.03] as significant risk factors. Current or prior history of treatment with d-drug was not a significant risk factor for incident DSP in subjects who had previously tolerated d-drug treatment without developing a toxic DSP. Age and low CD4 þ are risk factors for incident DSP. However, current or prior history of d-drug treatment is not a significant risk factor for incident DSP in subjects who had previously tolerated d-drug treatment without developing a toxic DSP.

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“…Most recently, it has been revealed that DSP affects 36% of patients under HAART. ddI was one of the important risk factors (Skopelitis et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Neurotoxicity caused by didanosine on cultured dorsal root ganglion neurons

Liu

Yang

et al. 2007

Cell Biol Toxicol

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The purpose of the present study was to investigate whether didanosine (ddI) directly causes morphological and ultrastructural abnormalities of dorsal root ganglion (DRG) neurons in vitro. Dissociated DRG cells and organotypic DRG explants from embryonic 15-day-old Wistar rats were cultured for 3 days and then exposed to ddI (1 microg/ml, 5 microg/ml, 10 microg/ml, and 20 microg/ml) for another 3 days and 6 days, respectively. Neurons cultured continuously in medium served as normal controls. The diameter of the neuronal cell body and neurite length were measured in dissociated DRG cell cultures. Neuronal ultrastructural changes were observed in both culture models. ddI induced dose-dependent decreases in neurite number, length of the longest neurite in each neuron, and total neurite length per neuron in dissociated DRG cell cultures with 3 days treatment. There were no morphological changes seen in organotypic DRG cultures even with longer exposure time (6 days). But ddI induced ultrastructural changes in both culture models. Ultrastructural abnormalities included loss of cristae in mitochondria, clustering of microtubules and neurofilaments, accumulation of glycogen-like granules, and emergence of large dense particles between neurites or microtubules. Lysosome-like large particles emerged inconstantly in neurites. ddI induced a neurite retraction or neurite loss in a dose-dependent manner in dissociated DRG neurons, suggesting that ddI may partially contribute to developing peripheral neuropathy. Cytoskeletal rearrangement and ultrastructural abnormalities caused by ddI in both culture models may have a key role in neurite degeneration.

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Distal sensory polyneuropathy in HIV-positive patients in the HAART era: an entity underestimated by clinical examination

Cited by 35 publications

References 0 publications

Chemokines and the pathophysiology of neuropathic pain

Chemokines and the pathophysiology of neuropathic pain

Incident Neuropathy in HIV-Infected Patients on HAART

Neurotoxicity caused by didanosine on cultured dorsal root ganglion neurons

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