TY - JOUR
T1 - Proinflammatory chemokines, such as C-C chemokine ligand 3, desensitize μ-opioid receptors on dorsal root ganglia neurons
AU - Zhang, Ning
AU - Rogers, Thomas J.
AU - Caterina, Michael
AU - Oppenheim, Joost J.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2004/7/1
Y1 - 2004/7/1
N2 - 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.
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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U2 - 10.4049/jimmunol.173.1.594
DO - 10.4049/jimmunol.173.1.594
M3 - Article
C2 - 15210821
AN - SCOPUS:2942731605
SN - 0022-1767
VL - 173
SP - 594
EP - 599
JO - Journal of Immunology
JF - Journal of Immunology
IS - 1
ER -