Neuroinflammation in HIV-Related Neuropathic Pain

Abstract

In the management of human immunodeficiency virus (HIV) infection around the world, chronic complications are becoming a new problem along with the prolonged life expectancy. Chronic pain is widespread in HIV infected patients and even affects those with a low viral load undergoing long-term treatment with antiviral drugs, negatively influencing the adherence to disease management and quality of life. A large proportion of chronic pain is neuropathic pain, which defined as chronic pain caused by nervous system lesions or diseases, presenting a series of nervous system symptoms including both positive and negative signs. Injury caused by HIV protein, central and peripheral sensitization, and side effects of antiretroviral therapy lead to neuroinflammation, which is regarded as a maladaptive mechanism originally serving to promote regeneration and healing, constituting the main mechanism of HIV-related neuropathic pain. Gp120, as HIV envelope protein, has been found to be the major toxin that induces neuropathic pain. Particularly, the microglia, releasing numerous pro-inflammatory substances (such as TNFα, IL-1β, and IL-6), not only sensitize the neurons but also are the center part of the crosstalk bridging the astrocytes and oligodendrocytes together forming the central sensitization during HIV infection, which is not discussed detailly in recent reviews. In the meantime, some NRTIs and PIs exacerbate the neuroinflammation response. In this review, we highlight the importance of clarifying the mechanism of HIV-related neuropathic pain, and discuss about the limitation of the related studies as future research directions.

Genetic and functional evidence for gp130/IL6ST-induced transient receptor potential ankyrin 1 upregulation in uninjured but not injured neurons in a mouse model of neuropathic pain

“…54,72 The IL-6/IL-6R/gp130 axis is critically involved in neuropathic pain induced by nerve injury, chronic inflammation, cancer, chemotherapy, diabetes, as well as HIV and herpes infections. 39,51,80,99 Classical as well as trans-signalling cascades have been extensively studied, and therapeutic interventions targeting the IL-6 pathway have been approved mostly for chronic inflammatory disorders. 13,55 Several treatment strategies have been used targeting IL-6, IL-6R, or gp130 as well as their soluble forms, eg, sgp130Fc that offers promising benefit for diabetic neuropathy and inflammatory disease by specifically blocking IL-6 transsignaling.…”

Progress on the Elucidation of the Antinociceptive Effect of Ginseng and Ginsenosides in Chronic Pain

“…Approximately 7–10% of the population suffers from pain with neuropathic characteristics ( Wright and Rizzolo, 2017 ). The pathogenesis of neuropathic pain is complicated, spinal cord injury ( Lee et al, 2021b ), immune diseases ( Lu H. J. et al, 2021 ), diabetes ( Rosenberger et al, 2020 ), and cancers ( Fallon, 2013 ) can all cause neuropathic pain. The effect of traditional opioid analgesics and non-steroidal anti-inflammatory drugs on neuropathic pain are less than ideal.…”

Highly active antiretroviral therapy-silver nanoparticle conjugate interacts with neuronal and glial cells and alleviates anxiety-like behaviour in streptozotocin-induced diabetic rats

“…The increased ROS damage vital cellular components (e.g., DNA, lipids, and proteins) in glucoregulatory tissues leading to insulin resistance or compromised insulin synthesis, thereby promoting hyperglycemia ( Han, 2016 ). Also, HAART has been linked with mitochondrial damage and subsequently increases the risk of neuropathy and neuroinflammation ( Lin et al, 2018 , Lu et al, 2021 ). Chronic administration of HAART to HIV positive patients has been reported to cause neuroinflammation, changes in astrocyte mitochondrial membrane and mitochondrial ROS production in animal experiments ( Bertrand et al, 2021 , Lawal et al, 2022 ).…”