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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

kin-resident dendritic cells mediate postoperative pain via CCR4 on sensory neuron

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Author(s):
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Silva, Jaqueline Raymondi [1, 2] ; Iftinca, Mircea [3] ; Gomes, Francisco I. Fernandes [4] ; Segal, Julia P. [1] ; Smith, Olivia M. A. [1] ; Bannerman, Courtney A. [1] ; Mendes, Atlante Silva [4] ; Defaye, Manon [3] ; Robinson, Madeline E. C. [1] ; Gilron, Ian [1, 2, 5, 6] ; Cunha, Thiago Mattar [4] ; Altier, Christophe [3] ; Ghasemlou, Nader [1, 2, 5]
Total Authors: 13
Affiliation:
[1] Queens Univ, Dept Biomed & Mol Sci, Kingston, ON K7L 3N6 - Canada
[2] Queens Univ, Dept Anesthesiol & Perioperat Med, Kingston, ON K7L 3N6 - Canada
[3] Univ Calgary, Cumming Sch Med, Dept Physiol & Pharmacol, Calgary, AB T2N 4N1 - Canada
[4] Univ Sao Paulo, Ribeirao Preto Med Sch, Ctr Res Inflammatory Dis, BR-1409900 Sao Paulo - Brazil
[5] Queens Univ, Ctr Neurosci Studies, Kingston, ON K7L 3N6 - Canada
[6] Queens Univ, Sch Policy Studies, Kingston, ON K7L 3N6 - Canada
Total Affiliations: 6
Document type: Journal article
Source: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA; v. 119, n. 4 JAN 25 2022.
Web of Science Citations: 0
Abstract

Inflammatory pain, such as hypersensitivity resulting from surgical tissue injury, occurs as a result of interactions between the immune and nervous systems with the orchestrated recruitment and activation of tissue-resident and circulating immune cells to the site of injury. Our previous studies identified a central role for Ly6C(low) myeloid cells in the pathogenesis of postoperative pain. We now show that the chemokines CCL17 and CCL22, with their cognate receptor CCR4, are key mediators of this response. Both chemokines are up-regulated early after tissue injury by skinresident dendritic and Langerhans cells to act on peripheral sensory neurons that express CCR4. CCL22, and to a lesser extent CCL17, elicit acute mechanical and thermal hypersensitivity when administered subcutaneously; this response abrogated by pharmacological blockade or genetic silencing of CCR4. Electrophysiological assessment of dissociated sensory neurons from naive and postoperative mice showed that CCL22 was able to directly activate neurons and enhance their excitability after injury. These responses were blocked using C 021 and small interfering RNA (siRNA)-targeting CCR4. Finally, our data show that acute postoperative pain is significantly reduced in mice lacking CCR4, wildtype animals treated with CCR4 antagonist/siRNA, as well as transgenic mice depleted of dendritic cells. Together, these results suggest an essential role for the peripheral CCL17/22:CCR4 axis in the genesis of inflammatory pain via direct communication between skin-resident dendritic cells and sensory neurons, opening therapeutic avenues for its control. (AU)

FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
Grantee:Fernando de Queiroz Cunha
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC