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Gp120 induced neuropathic pain

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https://www.readbyqxmd.com/read/27350758/antinociceptive-effects-of-topical-mepivacaine-in-a-rat-model-of-hiv-associated-peripheral-neuropathic-pain
#1
Jacqueline Sagen, Daniel A Castellanos, Aldric T Hama
BACKGROUND: A consequence of HIV infection is sensory neuropathy, a debilitating condition that degrades the quality of life of HIV patients. Furthermore, life-extending antiretroviral treatment may exacerbate HIV sensory neuropathy. Analgesics that relieve other neuropathic pains show little or no efficacy in ameliorating HIV sensory neuropathy. Thus, there is a need for analgesics for people with this particular pain. While lidocaine is used in the management of painful peripheral neuropathies, another local anesthetic mepivacaine, with a potentially improved bioavailability, could be utilized for the management of HIV neuropathic pain...
2016: Journal of Pain Research
https://www.readbyqxmd.com/read/27090160/spinal-cpeb-mtros-cbp-signaling-pathway-contributes-to-perineural-hiv-gp120-with-ddc-related-neuropathic-pain-in-rats
#2
Takafumi Iida, Hyun Yi, Shue Liu, Wan Huang, Hirotsugu Kanda, David A Lubarsky, Shuanglin Hao
Human immunodeficiency virus (HIV) patients treated with nucleoside reverse transcriptase inhibitors (NRTIs), have been known to develop neuropathic pain. While there has been a major shift away from some neurotoxic NRTIs in current antiretroviral therapy, a large number of HIV patients alive today have previously received them, and many have developed painful peripheral neuropathy. The exact mechanisms by which HIV with NRTIs contribute to the development of neuropathic pain are not known. Previous studies suggest that cytoplasmic polyadenylation element-binding protein (CPEB), reactive oxygen species (ROS), and cAMP-response element-binding protein (CREB)-binding protein (CBP), are involved in the neuroimmunological diseases including inflammatory/neuropathic pain...
July 2016: Experimental Neurology
https://www.readbyqxmd.com/read/26752351/hsv-vector-mediated-gad67-suppresses-neuropathic-pain-induced-by-perineural-hiv-gp120-in-rats-through-inhibition-of-ros-and-wnt5a
#3
H Kanda, M Kanao, S Liu, H Yi, T Iida, R C Levitt, K A Candiotti, D A Lubarsky, S Hao
Human immunodeficiency virus (HIV)-related neuropathic pain is a debilitating chronic condition that is severe and unrelenting. Despite the extensive research, the exact neuropathological mechanisms remain unknown, which hinders our ability to develop effective treatments. Loss of GABAergic tone may have an important role in the neuropathic pain state. Glutamic acid decarboxylase 67 (GAD67) is one of the isoforms that catalyze GABA synthesis. Here, we used recombinant herpes simplex virus (HSV-1) vectors that encode gad1 gene to evaluate the therapeutic potential of GAD67 in peripheral HIV gp120-induced neuropathic pain in rats...
April 2016: Gene Therapy
https://www.readbyqxmd.com/read/26418124/inhibition-of-mitochondrial-fission-protein-reduced-mechanical-allodynia-and-suppressed-spinal-mitochondrial-superoxide-induced-by-perineural-human-immunodeficiency-virus-gp120-in-rats
#4
Hirotsugu Kanda, Shue Liu, Takafumi Iida, Hyun Yi, Wan Huang, Roy C Levitt, David A Lubarsky, Keith A Candiotti, Shuanglin Hao
BACKGROUND: Mitochondria play an important role in many cellular and physiologic functions. Mitochondria are dynamic organelles, and their fusion and fission regulate cellular signaling, development, and mitochondrial homeostasis. The most common complaint of human immunodeficiency virus (HIV)-sensory neuropathy is pain on the soles in patients with HIV, but the exact molecular mechanisms of HIV neuropathic pain are not clear. In the present study, we investigated the role of mitochondrial dynamin-related protein 1 (Drp1, a GTPase that mediates mitochondrial fission) in the perineural HIV coat glycoprotein gp120-induced neuropathic pain state...
January 2016: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/25851180/gene-transfer-of-glutamic-acid-decarboxylase-67-by-herpes-simplex-virus-vectors-suppresses-neuropathic-pain-induced-by-human-immunodeficiency-virus-gp120-combined-with-ddc-in-rats
#5
Megumi Kanao, Hirotsugu Kanda, Wan Huang, Shue Liu, Hyun Yi, Keith A Candiotti, David A Lubarsky, Roy C Levitt, Shuanglin Hao
BACKGROUND: Human immunodeficiency virus (HIV)-related painful sensory neuropathies primarily consist of the HIV infection-related distal sensory polyneuropathy and antiretroviral toxic neuropathies. Pharmacotherapy provides only partial relief of pain in patients with HIV/acquired immune deficiency syndrome because little is known about the exact neuropathological mechanisms for HIV-associated neuropathic pain (NP). Hypofunction of γ-aminobutyric acid (GABA) GABAergic inhibitory mechanisms has been reported after peripheral nerve injury...
June 2015: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/25489421/the-protective-effects-of-igf-1-on-different-subpopulations-of-drg-neurons-with-neurotoxicity-induced-by-gp120-and-dideoxycytidine-in-vitro
#6
Lin Lu, Haixia Dong, Guixiang Liu, Bin Yuan, Yizhao Li, Huaxiang Liu
Peripheral neuropathy induced by human immunodeficiency virus (HIV) infection and antiretroviral therapy is not only difficult to distinguish in clinical practice, but also difficult to relieve the pain symptoms by analgesics because of the severity of the disease at the later stage. Hence, to explore the mechanisms of HIV-related neuropathy and find new therapeutic options are particularly important for relieving neuropathic pain symptoms of the patients. In the present study, primary cultured embryonic rat dorsal root ganglion (DRG) neurons were used to determine the neurotoxic effects of HIV-gp120 protein and/or antiretroviral drug dideoxycytidine (ddC) and the therapeutic actions of insulin-like growth factor-1 (IGF-1) on gp120- or ddC-induced neurotoxicity...
November 2014: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/25486617/attenuation-of-persistent-pain-related-behavior-by-fatty-acid-amide-hydrolase-faah-inhibitors-in-a-rat-model-of-hiv-sensory-neuropathy
#7
COMPARATIVE STUDY
Farinaz Nasirinezhad, Stanislava Jergova, James P Pearson, Jacqueline Sagen
Distal sensory neuropathies are a hallmark of HIV infections and can result in persistent and disabling pain despite advances in antiretroviral therapies. HIV-sensory neuropathic (HIV-SN) pain may be amenable to cannabinoid treatment, but currently available agonist treatments are limited by untoward side effects and potential for abuse in this patient population. Fatty acid amide hydrolase (FAAH) inhibitors may offer an alternative approach by inhibiting the degradation of endocannabinoids with purportedly fewer untoward CNS side effects...
August 2015: Neuropharmacology
https://www.readbyqxmd.com/read/25137003/interleukin-10-mediated-by-herpes-simplex-virus-vectors-suppresses-neuropathic-pain-induced-by-human-immunodeficiency-virus-gp120-in-rats
#8
Wenwen Zheng, Wan Huang, Shue Liu, Roy C Levitt, Keith A Candiotti, David A Lubarsky, Shuanglin Hao
BACKGROUND: Human immunodeficiency virus (HIV)-associated sensory neuropathy is a common neurological complication of HIV infection affecting up to 30% of HIV-positive individuals. However, the exact neuropathological mechanisms remain unknown, which hinders our ability to develop effective treatments for HIV-related neuropathic pain (NP). In this study, we tested the hypothesis that inhibition of proinflammatory factors with overexpression of interleukin (IL)-10 reduces HIV-related NP in a rat model...
September 2014: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/25078297/il-10-mediated-by-herpes-simplex-virus-vector-reduces-neuropathic-pain-induced-by-hiv-gp120-combined-with-ddc-in-rats
#9
Wenwen Zheng, Wan Huang, Shue Liu, Roy C Levitt, Keith A Candiotti, David A Lubarsky, Shuanglin Hao
BACKGROUND: HIV-associated sensory neuropathy affects over 50% of HIV patients and is a common peripheral nerve complication of HIV infection and highly active antiretroviral therapy (HAART). Evidence shows that painful HIV sensory neuropathy is influenced by neuroinflammatory events that include the proinflammatory molecules, MAP Kinase, tumor necrosis factor-α (TNFα), stromal cell-derived factor 1-α (SDF1α), and C-X-C chemokine receptor type 4 (CXCR4). However, the exact mechanisms of painful HIV sensory neuropathy are not known, which hinders our ability to develop effective treatments...
2014: Molecular Pain
https://www.readbyqxmd.com/read/24451118/hsv-mediated-p55tnfsr-reduces-neuropathic-pain-induced-by-hiv-gp120-in-rats-through-cxcr4-activity
#10
W Huang, W Zheng, S Liu, W Zeng, R C Levitt, K A Candiotti, D A Lubarsky, S Hao
Human immunodeficiency virus (HIV)-related neuropathic pain is a debilitating chronic condition that is severe and unrelenting. Despite extensive research, the detailed neuropathological mechanisms remain unknown, which hinders our ability to develop effective treatments. In this study, we investigated the role of proinflammatory molecules, tumor necrosis factor-α (TNFα), CXCR4 and stromal-derived factor-1 α (SDF1α), in the L4/5 dorsal root ganglia (DRG) and the spinal dorsal horn in HIV gp120 protein-mediated neuropathic pain...
March 2014: Gene Therapy
https://www.readbyqxmd.com/read/21599974/glial-tnf%C3%AE-in-the-spinal-cord-regulates-neuropathic-pain-induced-by-hiv-gp120-application-in-rats
#11
Wenwen Zheng, Handong Ouyang, Xuexing Zheng, Shue Liu, Marina Mata, David J Fink, Shuanglin Hao
BACKGROUND: HIV-associated sensory neuropathy (HIV-SN) is one of the most common forms of peripheral neuropathy, affecting about 30% of people with acquired immune deficiency syndrome (AIDS). The symptoms of HIV-SN are dominated by neuropathic pain. Glia activation in the spinal cord has become an attractive target for attenuating chronic pain. This study will investigate the role of spinal TNFα released from glia in HIV-related neuropathic pain. RESULTS: Peripheral gp120 application into the rat sciatic nerve induced mechanical allodynia for more than 7 weeks, and upregulated the expression of spinal TNFα in the mRNA and the protein levels at 2 weeks after gp120 application...
2011: Molecular Pain
https://www.readbyqxmd.com/read/17761732/characterization-of-rodent-models-of-hiv-gp120-and-anti-retroviral-associated-neuropathic-pain
#12
Victoria C J Wallace, Julie Blackbeard, Andrew R Segerdahl, Fauzia Hasnie, Timothy Pheby, Stephen B McMahon, Andrew S C Rice
A distal symmetrical sensory peripheral neuropathy is frequently observed in people living with Human Immunodeficiency Virus Type 1 (HIV-1). This neuropathy can be associated with viral infection alone, probably involving a role for the envelope glycoprotein gp120; or a drug-induced toxic neuropathy associated with the use of nucleoside analogue reverse transcriptase inhibitors as a component of highly active anti-retroviral therapy. In order to elucidate the mechanisms underlying drug-induced neuropathy in the context of HIV infection, we have characterized pathological events in the peripheral and central nervous system following systemic treatment with the anti-retroviral agent, ddC (Zalcitabine) with or without the concomitant delivery of HIV-gp120 to the rat sciatic nerve (gp120+ddC)...
October 2007: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/17433546/pharmacological-behavioural-and-mechanistic-analysis-of-hiv-1-gp120-induced-painful-neuropathy
#13
Victoria C J Wallace, Julie Blackbeard, Timothy Pheby, Andrew R Segerdahl, Meirion Davies, Fauzia Hasnie, Susan Hall, Stephen B McMahon, Andrew S C Rice
A painful neuropathy is frequently observed in people living with human immunodeficiency virus type 1 (HIV-1). The HIV coat protein, glycoprotein 120 (gp120), implicated in the pathogenesis of neurological disorders associated with HIV, is capable of initiating neurotoxic cascades via an interaction with the CXCR4 and/or CCR5 chemokine receptors, which may underlie the pathogenesis of HIV-associated peripheral neuropathic pain. In order to elucidate the mechanisms underlying HIV-induced painful peripheral neuropathy, we have characterised pathological events in the peripheral and central nervous system following application of HIV-1 gp120 to the rat sciatic nerve...
December 15, 2007: Pain
https://www.readbyqxmd.com/read/16262636/involvement-of-spinal-cord-nuclear-factor-kappab-activation-in-rat-models-of-proinflammatory-cytokine-mediated-pain-facilitation
#14
COMPARATIVE STUDY
Annemarie Ledeboer, Michael Gamanos, Wenmin Lai, David Martin, Steven F Maier, Linda R Watkins, Ning Quan
Proinflammatory cytokines, such as interleukin-1beta and tumour necrosis factor-alpha, are released by activated glial cells in the spinal cord and play a major role in pain facilitation. These cytokines exert their actions, at least partially, through the activation of the transcription factor, nuclear factor kappaB (NF-kappaB). In turn, NF-kappaB regulates the transcription of many inflammatory mediators, including cytokines. We have previously shown that intrathecal injection of the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein, gp120, induces mechanical allodynia via the release of proinflammatory cytokines...
October 2005: European Journal of Neuroscience
https://www.readbyqxmd.com/read/15836971/minocycline-attenuates-mechanical-allodynia-and-proinflammatory-cytokine-expression-in-rat-models-of-pain-facilitation
#15
Annemarie Ledeboer, Evan M Sloane, Erin D Milligan, Matthew G Frank, John H Mahony, Steven F Maier, Linda R Watkins
Activated glial cells (microglia and astroglia) in the spinal cord play a major role in mediating enhanced pain states by releasing proinflammatory cytokines and other substances thought to facilitate pain transmission. In the present study, we report that intrathecal administration of minocycline, a selective inhibitor of microglial cell activation, inhibits low threshold mechanical allodynia, as measured by the von Frey test, in two models of pain facilitation. In a rat model of neuropathic pain induced by sciatic nerve inflammation (sciatic inflammatory neuropathy, SIN), minocycline delayed the induction of allodynia in both acute and persistent paradigms...
May 2005: Pain
https://www.readbyqxmd.com/read/15501197/spinal-gap-junctions-potential-involvement-in-pain-facilitation
#16
Leah E Spataro, Evan M Sloane, Erin D Milligan, Julie Wieseler-Frank, Diana Schoeniger, Brian M Jekich, Ruth M Barrientos, Steven F Maier, Linda R Watkins
UNLABELLED: Glia are now recognized as important contributors in pathological pain creation and maintenance. Spinal cord glia exhibit extensive gap junctional connectivity, raising the possibility that glia are involved in the contralateral spread of excitation resulting in mirror image pain. In the present experiments, the gap junction decoupler carbenoxolone was administered intrathecally after induction of neuropathic pain in response to sciatic nerve inflammation (sciatic inflammatory neuropathy) or partial nerve injury (chronic constriction injury)...
September 2004: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/11311327/peripheral-nerve-exposure-to-hiv-viral-envelope-protein-gp120-induces-neuropathic-pain-and-spinal-gliosis
#17
U Herzberg, J Sagen
Painful sensory neuropathy is a common and debilitating consequence of human immunodeficiency virus (HIV). The underlying causes of neuropathic pain are most likely not due to direct infection of the nervous system by active virus. The goal of this study was to determine whether epineural exposure to the HIV-1 envelope protein gp120 could lead to chronic painful peripheral neuropathy. Two doses of gp120 or BSA control were transiently delivered epineurally via oxidized cellulose wrapped around the rat sciatic nerve...
May 1, 2001: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/7999315/hiv-related-neuronal-injury-potential-therapeutic-intervention-with-calcium-channel-antagonists-and-nmda-antagonists
#18
REVIEW
S A Lipton
Perhaps as many as 25-50% of adult patients and children with acquired immunodeficiency syndrome (AIDS) eventually suffer from neurological manifestations, including dysfunction of cognition, movement, and sensation. How can human immunodeficiency virus type 1 (HIV-1) result in neuronal damage if neurons themselves are for all intents and purposes not infected by the virus? This article reviews a series of experiments leading to a hypothesis that accounts at least in part for the neurotoxicity observed in the brains of AIDS patients...
April 1994: Molecular Neurobiology
https://www.readbyqxmd.com/read/7847672/aids-related-dementia-and-calcium-homeostasis
#19
REVIEW
S A Lipton
Approximately a third of adults and half of children with acquired immunodeficiency syndrome (AIDS) eventually suffer from neurological manifestations, including dysfunction of cognition, movement, and sensation. Among the various pathologies reported in the brain of patients with AIDS is neuronal injury and loss. A paradox arises, however, because neurons themselves are for all intents and purposes not infected by human immunodeficiency virus type 1 (HIV-1). This paper reviews evidence suggesting that at least part of the neuronal injury observed in the brain of AIDS patients is related to excessive influx of Ca2+...
December 15, 1994: Annals of the New York Academy of Sciences
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