Neuron-associated macrophage proliferation in the sensory ganglia is associated with peripheral nerve injury-induced neuropathic pain involving CX3CR1 signaling
Center for Research in Inflammatory Diseases (CRID), Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil; Graduate Program in Basic and Applied Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
Center for Research in Inflammatory Diseases (CRID), Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil; Graduate Program in Basic and Applied Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
Marcela Davoli-Ferreira
Center for Research in Inflammatory Diseases (CRID), Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil; Graduate Program in Basic and Applied Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil; Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Canada
Francisco Isaac F Gomes
Center for Research in Inflammatory Diseases (CRID), Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil
Atlante Mendes
Center for Research in Inflammatory Diseases (CRID), Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil
Maria CM Cavallini
Center for Research in Inflammatory Diseases (CRID), Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil; Graduate Program in Basic and Applied Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
Miriam M Fonseca
Center for Research in Inflammatory Diseases (CRID), Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil; Department of Anesthesiology, Pain Mechanisms Laboratory, Wake Forest University School of Medicine, Winston-Salem, United States
Samara Damasceno
Center for Research in Inflammatory Diseases (CRID), Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil
Larissa P Andrade
Center for Research in Inflammatory Diseases (CRID), Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil; Graduate Program in Basic and Applied Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
Marco Colonna
Department of Pathology and Immunology, Washington University School of Medicine in Saint Louis, Saint Louis, United States
Cyril Rivat
Univ Montpellier, Montpellier, France; Inserm U-1298, Institut des Neurosciences de Montpellier, Montpellier, France
Fernando Q Cunha
Center for Research in Inflammatory Diseases (CRID), Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil
José C Alves-Filho
Center for Research in Inflammatory Diseases (CRID), Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil
Center for Research in Inflammatory Diseases (CRID), Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil
Resident macrophages are distributed across all tissues and are highly heterogeneous due to adaptation to different tissue-specific environments. The resident macrophages of the sensory ganglia (sensory neuron-associated macrophages, sNAMs) are in close contact with the cell body of primary sensory neurons and might play physiological and pathophysiological roles. After peripheral nerve injury, there is an increase in the population of macrophages in the sensory ganglia, which have been implicated in different conditions, including neuropathic pain development. However, it is still under debate whether macrophage accumulation in the sensory ganglia after peripheral nerve injury is due to the local proliferation of resident macrophages or a result of blood monocyte infiltration. Here, we confirmed that the number of macrophages increased in the sensory ganglia after the spared nerve injury (SNI) model in mice. Using different approaches, we found that the increase in the number of macrophages in the sensory ganglia after SNI is a consequence of the proliferation of resident CX3CR1+ macrophages, which participate in the development of neuropathic pain, but not due to infiltration of peripheral blood monocytes. These proliferating macrophages are the source of pro-inflammatory cytokines such as TNF and IL-1b. In addition, we found that CX3CR1 signaling is involved in the sNAMs proliferation and neuropathic pain development after peripheral nerve injury. In summary, these results indicated that peripheral nerve injury leads to sNAMs proliferation in the sensory ganglia in a CX3CR1-dependent manner accounting for neuropathic pain development. In conclusion, sNAMs proliferation could be modulated to change pathophysiological conditions such as chronic neuropathic pain.
