Inflammation contributes to neuropathic pain, but the mechanisms by which neurons and inflammatory cells interact are unclear. Simeoli et al. demonstrated the release of exosomes containing miR-21 from the cell bodies of cultured mouse sensory neurons following treatment with a noxious substance. They further showed that these exosomes can be engulfed by macrophages, causing these cells to adopt a pro-inflammatory phenotype. Inhibition or deletion of miR-21 reduced the number of inflammatory macrophages in the spinal cord and mechanical hypersensitivity after nerve injury, confirming its role in neuron–macrophage communication.