Proinflammatory chemokines, such as C-C chemokine ligand 3, desensitize μ-opioid receptors on dorsal root ganglia neurons

Ning Zhang, Thomas J. Rogers, Michael Caterina, Joost J. Oppenheim

Research output: Contribution to journalArticle

Abstract

Pain is one of the hallmarks of inflammation. Opioid receptors mediate antipain responses in both the peripheral nervous system and CNS. In the present study, pretreatment of CCR1:μ-opioid receptor/HEK293 cells with CCL3 (MIP-1α) induced internalization of μ-opioid receptors and severely impaired the μ-opioid receptor-mediated inhibition of cAMP accumulation. Immunohistochemical staining showed that CCR1 and μ-opioid receptors were coexpressed on small to medium diameter neurons in rat dorsal root ganglion. Analysis of ligand-induced calcium flux showed that both types of receptors were functional. Pretreatment of neurons with CCL3 exhibited an impaired [D-Ala 2,N-MePhe4,Gly-o15]enkephalin-elicited calcium response, indicative of the heterologous desensitization of μ-opioid receptors. Other chemokines, such as CCL2, CCL5, and CXCL8, exhibited similar inhibitory effects. Our data indicate that proinflammatory chemokines are capable of desensitizing μ-opioid receptors on peripheral sensory neurons, providing a novel potential mechanism for peripheral inflammation-induced hyperalgesia.

Original languageEnglish (US)
Pages (from-to)594-599
Number of pages6
JournalJournal of Immunology
Volume173
Issue number1
StatePublished - Jul 1 2004

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CC Chemokines
Spinal Ganglia
Opioid Receptors
Chemokines
Ligands
Neurons
CCR1 Receptors
Antipain
Inflammation
Calcium
Enkephalins
HEK293 Cells
Hyperalgesia
Peripheral Nervous System
Sensory Receptor Cells
Staining and Labeling
Pain

ASJC Scopus subject areas

  • Immunology

Cite this

Proinflammatory chemokines, such as C-C chemokine ligand 3, desensitize μ-opioid receptors on dorsal root ganglia neurons. / Zhang, Ning; Rogers, Thomas J.; Caterina, Michael; Oppenheim, Joost J.

In: Journal of Immunology, Vol. 173, No. 1, 01.07.2004, p. 594-599.

Research output: Contribution to journalArticle

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AB - Pain is one of the hallmarks of inflammation. Opioid receptors mediate antipain responses in both the peripheral nervous system and CNS. In the present study, pretreatment of CCR1:μ-opioid receptor/HEK293 cells with CCL3 (MIP-1α) induced internalization of μ-opioid receptors and severely impaired the μ-opioid receptor-mediated inhibition of cAMP accumulation. Immunohistochemical staining showed that CCR1 and μ-opioid receptors were coexpressed on small to medium diameter neurons in rat dorsal root ganglion. Analysis of ligand-induced calcium flux showed that both types of receptors were functional. Pretreatment of neurons with CCL3 exhibited an impaired [D-Ala 2,N-MePhe4,Gly-o15]enkephalin-elicited calcium response, indicative of the heterologous desensitization of μ-opioid receptors. Other chemokines, such as CCL2, CCL5, and CXCL8, exhibited similar inhibitory effects. Our data indicate that proinflammatory chemokines are capable of desensitizing μ-opioid receptors on peripheral sensory neurons, providing a novel potential mechanism for peripheral inflammation-induced hyperalgesia.

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