Faculty Collaboration Database

Chemokines and glycoprotein120 produce pain hypersensitivity by directly exciting primary nociceptive neurons. J Neurosci 2001 Jul 15;21(14):5027-35

Date

07/05/2001

Pubmed ID

11438578

Pubmed Central ID

PMC6762869

DOI

10.1523/JNEUROSCI.21-14-05027.2001

Scopus ID

2-s2.0-0035878073 (requires institutional sign-in at Scopus site)   421 Citations

Abstract

Human immunodeficiency virus-1 (HIV-1) infection is associated with numerous effects on the nervous system, including pain and peripheral neuropathies. We now demonstrate that cultured rat dorsal root ganglion (DRG) neurons express a wide variety of chemokine receptors, including those that are thought to act as receptors for the HIV-1 coat protein glycoprotein120 (gp120). Chemokines that activate all of the known chemokine receptors increased [Ca(2+)](i) in subsets of cultured DRG cells. Many neurons responded to multiple chemokines and also to bradykinin, ATP, and capsaicin. Immunohistochemical studies demonstrated the expression of the CXCR4 and CCR4 chemokine receptors on populations of DRG neurons that also expressed substance P and the VR1 vanilloid receptor. RT-PCR analysis confirmed the expression of CXCR4, CX3CR1, CCR4, and CCR5 mRNAs in DRG neurons. Chemokines and gp120 produced excitatory effects on DRG neurons and also stimulated the release of substance P. Chemokines and gp120 also produced allodynia after injection into the rat paw. Thus these results provide evidence that chemokines and gp120 may produce painful effects via direct actions on chemokine receptors expressed by nociceptive neurons. Chemokine receptor antagonists may be important therapeutic interventions in the pain that is associated with HIV-1 infection and inflammation.

Author List

Oh SB, Tran PB, Gillard SE, Hurley RW, Hammond DL, Miller RJ

Author

Robert W. Hurley MD, PhD Adjunct Professor of Anesthesiology and CTSI in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenosine Triphosphate
Animals
Bradykinin
Calcium
Capsaicin
Cells, Cultured
Chemokines
Fluorescent Dyes
Ganglia, Spinal
HIV Envelope Protein gp120
Hyperalgesia
Inflammation
Intracellular Fluid
Male
Neurons
Nociceptors
RNA, Messenger
Rats
Rats, Sprague-Dawley
Receptors, CCR4
Receptors, CXCR4
Receptors, Chemokine
Substance P