|Title||Decreased dopaminergic inhibition of pyramidal neurons in anterior cingulate cortex maintains chronic neuropathic pain.|
|Publication Type||Journal Article|
|Year of Publication||2021|
|Authors||Lançon K, Qu C, Navratilova E, Porreca F, Séguéla P|
|Date Published||2021 Nov 30|
|Keywords||Animals, Dopamine, Dopamine Agents, Gyrus Cinguli, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, Levodopa, Male, Membrane Potentials, Neuralgia, Potassium Channels, Pyramidal Cells, Rats, Rats, Sprague-Dawley, Receptors, Dopamine D1|
Pyramidal neurons in the anterior cingulate cortex (ACC), a prefrontal region involved in processing the affective components of pain, display hyperexcitability in chronic neuropathic pain conditions, and their silencing abolishes hyperalgesia. We show that dopamine, through D1 receptor (D1R) signaling, inhibits pyramidal neurons of mouse ACC by modulation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Activation of G-coupled D1R by dopamine induces the opening of HCN channels at physiological membrane potentials, driving a significant decrease in input resistance and excitability. Systemic L-DOPA in chronic neuropathic mice rescues HCN channel activity, normalizes pyramidal excitability in ACC, and blocks mechanical and thermal allodynia. Moreover, microinjection of a selective D1R agonist in the ACC relieves the aversiveness of ongoing neuropathic pain, while an ACC D1R antagonist blocks gabapentin- and lidocaine-evoked antinociception. We conclude that dopaminergic inhibition via D1R in ACC plays an analgesic role in physiological conditions and is decreased in chronic pain.
|Alternate Journal||Cell Rep|
|PubMed Central ID||PMC8728690|
|Grant List||R01 DA041809 / DA / NIDA NIH HHS / United States|
Decreased dopaminergic inhibition of pyramidal neurons in anterior cingulate cortex maintains chronic neuropathic pain.
Faculty Member Reference:
Frank Porreca, PhD