Related Experiment Video
Updated: May 17, 2026
![Autoradiographic Measurements of [14C]-Iodoantipyrine in Rat Brain Following Central Post-Stroke Pain](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F53947.jpg&w=3840&q=50)
Autoradiographic Measurements of [14C]-Iodoantipyrine in Rat Brain Following Central Post-Stroke Pain
Published on: July 18, 2016
Spinal microglial activation in rat models of neuropathic and osteoarthritic pain: an autoradiographic study using
T R Miller1, J B Wetter, M F Jarvis
1Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, USA. thomas.r.miller@abbott.com
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.
Insights
Spinal microglial activation, marked by peripheral benzodiazepine receptor (PBR)/translocator protein 18 kDa (TSPO) binding, is elevated in chronic neuropathic and osteoarthritic pain models. This finding suggests PBR/TSPO imaging agents could aid clinical pain research.
Area of Science:
- Neuroscience
- Pain Research
- Immunology
Background:
- Microglia, the central nervous system's immune cells, contribute to chronic pain after nerve injury.
- Activated microglia show increased expression of the peripheral benzodiazepine receptor (PBR)/translocator protein 18 kDa (TSPO).
Purpose of the Study:
- To investigate spinal microglial activation using PBR/TSPO ligand binding in rat pain models.
- To assess the utility of [(3)H]PK11195 binding as a marker for chronic pain-related microglial changes.
Main Methods:
- Radioligand binding autoradiography and filtration assays were used to measure [(3)H]PK11195 binding in rat spinal cords.
- Experimental pain models included neuropathic pain (spinal nerve ligation), osteoarthritic pain (MIA-OA), and inflammatory pain (CFA).
- Microglial activation was confirmed using anti-OX-42 (CD11b) immunostaining.
Main Results:
- Specific [(3)H]PK11195 binding significantly increased in the spinal cord ipsilateral to spinal nerve ligation (≥70%) and in the MIA-OA model (approx. 25%).
- Elevated binding was observed in chronic neuropathic and osteoarthritic pain models but not consistently in the inflammatory pain model.
- Increased CD11b expression in microglia correlated with elevated PBR/TSPO binding in the SNL and MIA-OA models.
Conclusions:
- [(3)H]PK11195 binding assays can serve as a marker for spinal microglial activation in experimental chronic neuropathic and osteoarthritic pain.
- These findings suggest potential clinical applications for PBR/TSPO imaging agents in pain research.
- The study highlights the role of spinal microglia in chronic pain states.
