Spinal microglial activation in rat models of neuropathic and osteoarthritic pain: an autoradiographic study using [3H]PK11195

Abstract

Background: Microglia serve as macrophage-like cells in the central nervous system, and activation of microglial cells in the spinal cord may contribute to ongoing pain following peripheral trauma or nerve injury. Following pronociceptive stimulation, activated microglia exhibit increased expression of the peripheral benzodiazepine receptor (PBR)/translocator protein 18 kDa (TSPO).

Methods: Using radioligand binding autoradiography and filtration assays, we examined the specific binding of the PBR/TSPO ligand [(3)H]PK11195 in spinal cords from the following rat experimental pain models: neuropathic pain induced by spinal nerve ligation (SNL), osteoarthritic pain induced by intraarticular injection of monosodium iodoacetate in the knee joint (MIA-OA), and subchronic inflammatory pain induced by intraplantar injection of complete Freund's adjuvant (CFA).

Results: Specific [(3)H]PK11195 binding in dorsal and ventral regions of lumbar spinal cord was increased by ≥70% ipsilateral to SNL. Also, specific [(3)H]PK11195 binding in the ipsilateral (injured) lumbar spinal cord was increased by approximately 25% in MIA-OA. In contrast to the data obtained in these chronic neuropathic and nociceptive pain models, specific [(3)H]PK11195 binding in the ipsilateral (injured) dorsal horn was elevated in only one of six CFA rats. Consistent with increased PBR/TSPO binding measured for SNL and MIA-OA rats, increased anti-OX-42 immunostaining of the cell surface microglial marker CD11b was observed in the ipsilateral spinal cord from these models.

Conclusions: These studies demonstrate that [(3)H]PK11195 binding assays may serve as a marker of spinal microglial activation in experimental models of chronic neuropathic or osteoarthritic pain, which may be translatable to clinical research through novel applications of PBR/TSPO imaging agents.