Hippocampal microglia’s role in neuropathic pain

Neuropathic pain often occurs alongside cognitive impairment, but the mechanisms behind this relationship remain unclear. A study in Behavioral Brain Research investigates the microglial activation in brain regions involved in emotion, memory and pain processing in male mice of a partial sciatic nerve ligation (PSNL) model. Two weeks post-injury, Iba1 and P2RY12 immunoreactivity—two markers of microglial activation—were significantly increased in the hippocampus and amygdala, but not the perirhinal cortex. Targeted microinjection of clodronate liposomes, depleting microglia, into the hippocampus, but not the amygdala, alleviated both mechanical allodynia and cognitive deficits. Hippocampal clodronate treatment also prevented the PSNL-induced degenerative changes in neuronal morphology. These results show that hippocampal microglial activation has an important role in both pain sensitivity and cognitive dysfunction following nerve injury. The results support that region-specific microglial activation contributes to neuropathic pain and show that the hippocampus can be a potential therapeutic target.

Original reference: Hisaoka-Nakashima, K. et al. Behav. Brain Res. 488, 115590 (2025)