Spinal glial activity in the tibial nerve transaction model (TNT) of neuropathic pain

Andrew Moss, Denise Richardson, Emma Winter, James Bilsland, Janet Nicholson, Sidath Katugampola, Ian Machin, Stephen Phillips. Pfizer, Sandwich, United Kingdom.

Microglia, are a type of immune cell that act as the first and main form of active defence in the central nervous system. Microglial proliferation, infiltration and activation in the spinal cord dorsal horn are key drivers in the establishment of central sensitisation and pain following peripheral nerve injury in rodents. These changes have been well described in a number of rodent neuropathic pain models. The tibial nerve transection (TNT) model of neuropathic pain is a peripheral nerve injury model, involving injury to a distal tibial branch of the sciatic nerve, which leads to a consistent and sustained mechanical and cold allodynia. The TNT model remains a relatively uncharacterised model, particularly in terms of the central glial response. The aim of this study was to characterise the spinal microglial response in the TNT model using immunohistochemical staining, taqman gene expression profiling and cytokine analysis. In addition, this study used the tritiated peripheral benzodiazepine receptor (PBR) ligand H3PK11195 to assess both the magnitude and the longevity of this central microglial response. In summary, this data clearly shows that in the TNT model there is a robust central microglial response that peaks in the first 14 days after the original insult and is maintained when examined at 85 days post injury.