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Brain‐derived neurotrophic factor modulates antiretroviral‐induced mechanical allodynia in the mouse
Author(s) -
Renn Cynthia L.,
Leitch Carmen C.,
Lessans Sherrie,
Rhee Peter,
McGuire W. Cameron,
Smith Barbara A.,
Traub Richard J.,
Dorsey Susan G.
Publication year - 2011
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22685
Subject(s) - allodynia , tropomyosin receptor kinase b , neurotrophic factors , neuropathic pain , brain derived neurotrophic factor , medicine , pharmacology , trk receptor , stavudine , anesthesia , hyperalgesia , nociception , immunology , receptor , viral load , human immunodeficiency virus (hiv) , antiretroviral therapy
Nucleoside reverse transcriptase inhibitors (NRTIs) are key components of HIV/AIDS treatment to reduce viral load. However, these drugs can induce chronic neuropathic pain, leading to increased morbidity in HIV patients. This study examines the role of brain‐derived neurotrophic factor (BDNF) in the spinal dorsal horn (SDH) in development of mechanical allodynia in male C57BL/6J mice treated with the NRTI stavudine (d4T). After d4T administration, mice developed increased neuronal activity and BDNF expression in the SDH and hind paw mechanical allodynia that was exacerbated by intrathecal BDNF administration. Intrathecal BDNF alone also increased neuronal activity and caused mechanical allodynia. Because excess BDNF amplified d4T‐induced mechanical allodynia and neuronal activity, the impact of decreasing BDNF in the SDH was investigated. After d4T, BDNF heterozygous mice were less allodynic than wild‐type littermates, which was negated by intrathecal BDNF administration. Finally, pretreatment with intrathecal trkB‐Fc chimera prior to d4T or administration of the tyrosine kinase inhibitor K252a 3 days after d4T blocked BDNF‐mediated signaling, significantly attenuated the development of mechanical allodynia (trkB‐Fc), and decreased neuronal activity (trkB‐Fc and K252a). Taken together, these findings provide evidence that BDNF in the SDH contributes to the development of NRTI‐induced painful peripheral neuropathy and may represent a new therapeutic opportunity. © 2011 Wiley‐Liss, Inc.