Abstract

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 here that dopamine, through D1-like receptor signaling, inhibits layer 2/3 pyramidal neurons of mouse ACC through modulation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Activation of Gs-coupled D1-like receptors 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 has anti-allodynic effects on mechanical and thermal responses. Moreover, microinjection of a selective D1-like agonist in ACC induces relief of ongoing pain in neuropathic animals. We conclude that dopaminergic inhibition in ACC plays an analgesic role in physiological conditions and is defective in chronic pain.

Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call