Microglia sustain anterior cingulate cortex neuronal hyperactivity in nicotine-induced pain

Area of Science:

• Neuroscience
• Pain Research
• Neuroinflammation

Background:

• Long-term smoking is a significant risk factor for chronic pain.
• Chronic nicotine exposure in rodents induces pain-like effects.
• The anterior cingulate cortex (ACC) is implicated in pain processing and substance abuse.

Purpose of the Study:

• To investigate alterations in ACC microglia due to chronic nicotine exposure.
• To examine the interaction between ACC microglia and neurons in nicotine-induced allodynia.
• To determine the role of ACC microglia in maintaining pain hypersensitivity.

Main Methods:

• A mouse model was used, administering nicotine water for 28 days.
• ACC brain slices underwent morphological analysis to assess microglial changes.
• In vivo calcium imaging and whole-cell patch clamp recorded ACC glutamatergic neuron excitability.

Main Results:

• Nicotine exposure reduced microglial process length and branch endpoints in the ACC.
• Glutamatergic neurons in the ACC exhibited hyperactivity in nicotine-treated mice.
• Inhibition of ACC neurons or microglia, or blocking the CX3CL1/CX3CR1 pathway, reduced nicotine-induced allodynia and microglial activation.

Conclusions:

• ACC microglia play a critical role in maintaining ACC neuronal hyperactivity.
• Microglial activation contributes to nociceptive hypersensitivity in chronic nicotine exposure.
• The CX3CL1-CX3CR1 pathway mediates neuron-microglia interactions in chronic nicotine-induced allodynia.