Neuron-associated macrophage proliferation in the sensory ganglia is associated with peripheral nerve injury-induced neuropathic pain involving CX3CR1 signaling

• Published in: eLife Vol. 12
• Main Authors: Guimarães, Rafaela M, Aníbal-Silva, Conceição E, Davoli-Ferreira, Marcela, Gomes, Francisco Isaac F, Mendes, Atlante, Cavallini, Maria C M, Fonseca, Miriam M, Damasceno, Samara, Andrade, Larissa P, Colonna, Marco, Rivat, Cyril, Cunha, Fernando Q, Alves-Filho, José C, Cunha, Thiago M
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 31.05.2023; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Animals; CCR2; Cell body; Cell Proliferation; CX3CR1; CX3CR1 protein; Cytokines; Experiments; Flow cytometry; Ganglia, Sensory; Ganglia, Spinal; Hyperalgesia; Immunology and Inflammation; Infections; Infiltration; Inflammation; Interleukin 1; Macrophages; Mice; Monocytes; nerve injury; Neuralgia; Neurons; Neutrophils; Peripheral blood; Peripheral Nerve Injuries - complications; Peripheral nerves; Peripheral neuropathy; Physiological aspects; Scientific equipment and supplies industry; Sensory neurons; Sensory Receptor Cells; United States; CX3CR1; monocytes; mouse; macrophages; inflammation; nerve injury; cytokines; immunology; CCR2
• DOI: 10.7554/eLife.78515
• ISSN: 2050-084X

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.