Related Experiment Video
Updated: Jun 21, 2026
Chronic Constriction Injury of the Rat's Infraorbital Nerve IoN-CCI to Study Trigeminal Neuropathic Pain
Published on: September 21, 2015
Microglia in the Rostral Ventromedial Medulla Mediate Synaptic Pruning via the C1q/C3-CR3 Signaling Pathway-A
Xilu Huang1,2,3, Jie Zeng1, Zhanwei Hu1,2,3
1Department of Anesthesiology, Stomatological Hospital of Chongqing Medical University, Chongqing, China.
Abstract:
The mechanism of chronic orofacial pain was investigated by examining the interaction between activated microglia, C1q, and neurons in the rostral ventromedial medulla (RVM) of rats with orofacial pain caused by temporomandibular joint injection of complete Freund's adjuvant (CFA). The results demonstrated that the pain threshold in the CFA group exhibited a continuous decline, reaching its lowest point on the third day. During the modeling process, administered daily stereotactic injections of ANX-005 and minocycline into the RVM, which resulted in a notable recovery in the rats' pain threshold and a significant increase in C1q/C3 and microglia in the RVM of CFA rats. The application of ANX-005 or minocycline resulted in a reduction in the expression of C1q/C3 and microglia. Notably, the expression of excitatory presynaptic membrane markers reduced, and the length and density of dendritic spines decreased on neurons in the RVM. Additionally, C1q was abundantly localized on excitatory presynaptic membranes and expressed in microglial lysosomes. Treatment with ANX-005 or minocycline resulted in a reduced number of immunofluorescence colocalizations and an elevated dendritic spine density. These findings indicate that initial orofacial pain induced by CFA and microglia in the RVM are involved in the pruning of excitatory presynaptic membranes through the complement C1q/C3-CR3 signaling pathway. This process results in a reduction in the proportion of excitatory synapses and a disruption in the physiological balance between RVM descending facilitation and descending inhibition. This leads to the predominance of descending facilitation in pain transmission in the RVM, which in turn facilitates the chronification of orofacial pain.
Insights
Chronic orofacial pain involves microglia and C1q in the RVM, leading to synapse loss. Treatments ANX-005 and minocycline restored pain thresholds by modulating this pathway.
Area of Science:
- Neuroscience
- Immunology
- Pain Research
Background:
- Chronic orofacial pain is a debilitating condition with complex underlying mechanisms.
- The rostral ventromedial medulla (RVM) plays a crucial role in pain modulation.
- Microglia activation and complement system components like C1q are implicated in neuroinflammation and pain.
Purpose of the Study:
- To investigate the role of activated microglia, C1q, and neuronal interactions in the RVM in the chronification of orofacial pain.
- To examine the therapeutic potential of ANX-005 and minocycline in mitigating pain and associated synaptic changes.
Main Methods:
- Rats with orofacial pain induced by complete Freund's adjuvant (CFA) were used.
- Stereotactic injections of ANX-005 and minocycline into the RVM were administered.
- Pain thresholds, C1q/C3 expression, microglia activation, and dendritic spine morphology were assessed.
Main Results:
- CFA induced a significant decrease in pain threshold, accompanied by increased C1q/C3 and microglia in the RVM.
- ANX-005 and minocycline treatment restored pain thresholds and reduced C1q/C3 and microglia levels.
- These treatments also decreased excitatory presynaptic markers and dendritic spine density, while increasing spine density upon recovery.
Conclusions:
- Orofacial pain chronification involves microglia-mediated pruning of excitatory synapses in the RVM via the C1q/C3-CR3 pathway.
- This pruning disrupts the balance of descending pain modulation, favoring facilitation and leading to chronic pain.
- ANX-005 and minocycline show promise in treating chronic orofacial pain by targeting this neuroinflammatory pathway.
Related Concept Videos
01:19Ligand-gated Ion Channels
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that include the...
01:20Pain