title: Establishment of a rodent model of HIV-associated sensory neuropathy.
abstract: Human immunodeficiency virus (HIV)-associated sensory neuropathy (SN) is the most common neurological complication of HIV infection in the current highly active antiretroviral therapy era. The painful sensory neuropathy is associated with the use of dideoxynucleoside antiretrovirals, and its development limits the choice of antiretroviral drugs in affected patients. There are presently no effective therapies for HIV-SN, and moreover there has been no robust animal model of HIV-SN in which candidate therapeutic agents can be tested. In this paper, we show that we have established a rodent model of HIV-SN by oral administration of a dideoxynucleoside drug, didanosine, to transgenic mice expressing the HIV coat protein gp120 under a GFAP promoter. The neuropathy in these rodents is characterized by distal degeneration of unmyelinated sensory axons, similar to the "dying back" pattern of C-fiber loss seen in patients with HIV-SN. This model will be useful in examining mechanisms of distal axonal degeneration and testing potential neuroprotective compounds that may prevent development of the sensory neuropathy.
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: Sanjay C
authors.initials: SC
authors.lastname: Keswani
authors.forename: Christelene
authors.initials: C
authors.lastname: Jack
authors.forename: Chunhua
authors.initials: C
authors.lastname: Zhou
authors.forename: Ahmet
authors.initials: A
authors.lastname: Höke
mesh_terms: D000818:Animals; D044966:Anti-Retroviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D016049:Didanosine / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D015497:HIV-1; D051379:Mice; D008822:Mice, Transgenic; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*
chemical_list: D044966:Anti-Retroviral Agents; D016049:Didanosine