Nociceptin inhibits calcium channel currents in a subpopulation of small nociceptive trigeminal ganglion neurons in mouse

1. The effects of nociceptin/orphanin FQ (N/OFQ) and opioid receptor agonis ts on voltage-activated calcium channel currents (I-Ca) were examined in ac utely isolated mouse trigeminal ganglion neurons using whole-cell patch-cla mp recordings. These effects were correlated with responses of the neurons to capsaicin and binding of Bandeiraea simplicifolia isolectin B4 (IB4). 2. Trigeminal neurons were divided into two populations based on the presen ce (type 2) or absence (type 1) of a prominent T-type I-Ca N/OFQ potently ( EC50 of 19 nm) inhibited high-voltage-activated (HVA) I-Ca in most (82%) sm all (capacitance < 12 pF) type 1 neurons, but few (9%) larger (< 12 pF) typ e 1 neurons. N/OFQ inhibited I-Ca in few (23%) type 2 cells, and did not af fect the T-type I-Ca in any cell. 3. The mu -opioid agonists DAMGO and morphine inhibited I-Ca in most type 1 neurons, more often (95% versus 77%) in the small cells. The inhibition of I-Ca by DAMGO and morphine was more efficacious in small versus large type I neurons. mu -Opioids did not inhibit I-Ca in type 2 neurons. 4. Most, small type 1 neurons were sensitive to capsaicin (93%) and bound I B4 (86%). Fewer larger type I neurons responded to capsaicin (30%) or bound IB4 (58%). Type 2 neurons did not respond to capsaicin, although some boun d IB4 (35%). 5. Thus, N/OFQ preferentially inhibits HVA I-Ca in a subpopulation of small nociceptive trigeminal ganglion neurons that is also highly sensitive mu - opioid agonist.