Microgliosis in the Spinal Dorsal Horn Early After Peripheral Nerve Injury Is Associated with Damage to Primary Afferent Aβ-Fibers

Neuropathic pain results from a lesion or disease affecting the somatosensory nervous system. Injury to primary afferent nerves leads to microgliosis in the spinal dorsal horn (SDH), which plays a crucial role in developing neuropathic pain. Within the SDH, primary afferent fibers broadly project, and microglia are nearly ubiquitously distributed under normal conditions. However, not all microglia react to injuries affecting primary afferent fibers, resulting in spatially heterogeneous microgliosis within the SDH. The mechanisms underlying this phenomenon remain elusive. In this study, the spatial relationship between microgliosis and the projections of injured nerves was investigated by generating mice that had expressed tdTomato in the fourth lumbar dorsal root ganglion (L4-DRG) neurons via intra-L4-spinal nerve (SpN) injection of adeno-associated viral vectors. After transection of the L4-SpN, we found that microgliosis in the SDH selectively occurred in the innervation territories of the injured primary afferent fibers. However, denervating transient receptor potential vanilloid 1 (TRPV1)-expressing primary afferent fibers in the SDH through intrathecal injection of capsaicin did not trigger microgliosis, nor did it influence the microgliosis induced by L4-SpN injury. Conversely, pharmacological damage to myelinated DRG neurons, including Aβ-fibers, was sufficient to induce microgliosis. Furthermore, L4-SpN injury also induced microgliosis in the gracile nucleus, which primarily receives innervation from Aβ-fibers. These findings suggest that microgliosis in the SDH shortly after peripheral nerve injury is predominantly associated with damage to primary afferent Aβ-fibers.