Differential microglial inflammatory responses in the spinal cord and brain towards the chronic neuropathic pain in rats

Abstract

Accumulating evidences suggest the involvement of immune cells, especially microglia, in development of the central nervous system and persistence of neuropathic pain after peripheral nerve injuries in adulthood, but the exact roles that microglia play are unclear. In this study, by utilizing an efficient and reproducible multicolor flow cytometry-based approach, we quantitatively evaluated both microgliosis and microglial activation in the lumbar spinal cord (SC), amygdala and prefrontal cortex (PFC) of adult male Hannover-Wistar rats in response to a chronic neuropathic pain induced by ligation of the tibial and common peroneal nerves (known as the spared nerve injury (SNI) model). When comparing the SNI and sham-operated rats, we observed increased microgliosis in the ipsi-lateral lumbar SC on both post-operative day (POD) 7 and 21, and a milder increase in the contralateral side of SC on POD21. Regarding microglial activation, we unexpectedly found increased numbers of the anti-inflammatory type of microglia (CD172a+MHCII-/+) in the ipsilateral lumbar SC but an opposite change in the contra-lateral PFC on POD21. Moreover, these inflammatory responses were accompanied by the mechanical allodynia and anxiety-related behaviors of the SNI rats. Our results suggest that microglia in the SC and brain are differentially activated by the spinal nerve injury, and that microglial responses in the SC do not necessarily develop into a proinflammatory prototype as many literature suggested.