Pharmacological treatment of painful HIV-associated sensory neuropathy

Pillay, Prinisha; Wadley, Antonia L.; Cherry, Catherine L.; Karstaedt, Alan; Kamerman, Peter R.

doi:10.7196/samjnew.7908

Cited by 6 publications

(2 citation statements)

References 20 publications

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“…About 6 ∼ 10% adults are tortured by CNP and this prevalence is significantly higher in specific conditions, such as age and obesity [ 2 , 3 ]. It is frequent in infectious diseases such as HIV and leprosy and in such non-infectious conditions as diabetes and traumatic injury, considerably decreasing patient's quality of life [ 4 – 7 ]. Due to poor knowledge of the mechanism of CNP progression, pharmacological interventions have limited efficacy in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

Effect and mechanism of inhibition of PI3K/Akt/mTOR signal pathway on chronic neuropathic pain and spinal microglia in a rat model of chronic constriction injury

et al. 2017

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ObjectiveTo explore the effects of inhibition of PI3K/Akt/mTOR signal pathway on chronic neuropathic pain (CNP) and spinal microglia in a rat model of chronic constriction injury (CCI).MethodsMale SD rats were assigned into control, sham, CCI, wortmannin, dimethyl sulfoxide (DMSO) and wortmannin-positive control groups. Paw withdrawal mechanical threshold (PWMT) and thermal withdrawal latency (TWL) were recorded. qRT-PCR and Western blotting were used to detect PI3K, Akt and mTOR expressions and their phosphorylation. OX-4 expression was detected by immunohistochemistry and glial fibrillary acidic protein (GFAP) and nerve growth factor (NGF) expressions by immunofluorescence.ResultsPWMT and TWL decreased in the CCI group than in the sham group on the 7th and 14th day after operation. Compared with the control and sham groups, the CCI group showed increased PI3K, Akt and mTOR mRNA expressions and elevated PI3K, p-Akt, p-mTOR and P70S6K protein expressions. More OX-42-positive cells and higher integrated optical density (IOD) of GFAP and NGF were found in the CCI group than the sham group at the 14th day after operation. Compared with the DMSO group, the wortmannin group had higher PWMT and TWL, decreased PI3K, Akt and mTOR mRNA expressions and reduced PI3K, p-Akt, p-mTOR and P70S6K protein expressions. Less OX-42-positive cells and lower IOD of GFAP and NGF were found in the wortmannin group than the DMSO group 14th day after operation.ConclusionInhibition of PI3K/Akt/mTOR signal pathway may alleviate CNP and reduce microglia and GFAP and NGF expressions in marrow in a rat model of CCI.

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Section: Introductionmentioning

confidence: 99%

Effect and mechanism of inhibition of PI3K/Akt/mTOR signal pathway on chronic neuropathic pain and spinal microglia in a rat model of chronic constriction injury

et al. 2017

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“…We have previously shown that elevated plasma sCD163 and RANTES (both of which are associated with myeloid cell activation and chemotaxis) correlates with reduced IENFD in SIV+ macaques 5 . HIV-PN does not typically respond to pain medicine 35,36 . Thus, identifying treatment options that target the cause of damage to the nerves or DRG neurons has great clinical implications.…”

Section: Discussionmentioning

confidence: 99%

An oral form of methylglyoxal-bis-guanylhydrazone reduces monocyte activation and traffic to the dorsal root ganglia in a primate model of HIV-peripheral neuropathy

et al. 2017

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Peripheral neuropathy (PN) is a major comorbidity of HIV infection that is caused in part by chronic immune activation. HIV-PN is associated with infiltration of monocytes/macrophages to the dorsal root ganglia (DRG) causing neuronal loss and formation of Nageotte nodules. Here, we used an oral form of methylglyoxal-bis-guanylhydrazone (MGBG), a polyamine biosynthesis inhibitor, to specifically reduce activation of myeloid cells. MGBG is selectively taken up by monocyte/macrophages in vitro and inhibits HIV p24 expression and DNA viral integration in macrophages. Here, MGBG was administered to nine SIV-infected, CD8-depleted rhesus macaques at 21 days post-infection (dpi). An additional nine SIV-infected, CD8-depleted rhesus macaques were used as untreated controls. Cell traffic to tissues was measured by in vivo BrdU-pulse labeling. MGBG treatment significantly diminished DRG histopathology and reduced the number of CD68+ and CD163+ macrophages in DRG tissue. The number of recently trafficked BrdU+ cells in the DRG was significantly reduced with MGBG treatment. Despite diminished DRG pathology, intraepidermal nerve fiber density (IENFD) did not recover after treatment with MGBG. These data suggest that MGBG alleviated DRG pathology and inflammation.

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Establishment and characterisation of a stavudine (d4T)-induced rat model of antiretroviral toxic neuropathy (ATN) using behavioural and pharmacological methods

et al. 2019

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Pharmacological treatment of painful HIV-associated sensory neuropathy

Cited by 6 publications

References 20 publications

Effect and mechanism of inhibition of PI3K/Akt/mTOR signal pathway on chronic neuropathic pain and spinal microglia in a rat model of chronic constriction injury

Effect and mechanism of inhibition of PI3K/Akt/mTOR signal pathway on chronic neuropathic pain and spinal microglia in a rat model of chronic constriction injury

An oral form of methylglyoxal-bis-guanylhydrazone reduces monocyte activation and traffic to the dorsal root ganglia in a primate model of HIV-peripheral neuropathy

Establishment and characterisation of a stavudine (d4T)-induced rat model of antiretroviral toxic neuropathy (ATN) using behavioural and pharmacological methods

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