PMC

Rats were microinjected with the dynamin inhibitory peptide (dyn-DN) or the scrambled peptide (dyn-scr) as a control prior to microinjection of DERM-A594 into the vlPAG. A: Pretreatment with dynamin-DN reduced the antinociceptive effect of microinjecting DERM-A594 into the vlPAG compared to pretreatment with the scrambled peptide. B: The number of DERM-A594 labeled cells was significantly decreased in rats pretreated with dynamin-DN compared to scrambled-dynamin pretreated animals. C, Panel 1, Labeling for DERM-A594 from a representative animal pretreated with scrambled-dynamin (left) compared to a representative animal pretreated with dynamin-DN (right).

Rats were administered internalization blockers prior to cumulative microinjections of dermorphin. A: Microinjection of dermorphin produced a dose dependent increase in hot plate latency. Antinociceptive potency was decreased in rats pretreated with dynamin-DN (dyn-DN) compared to scrambled dynamin (dyn-scr) pretreated animals. B: The potency of dermorphin-induced antinociception also was decreased in rats pretreated with ConA compared to saline-pretreated rats. C: The antinociceptive potency of microinjecting the GABA antagonist bicuculline into the vlPAG was not affected by pretreatment with dynamin-DN peptide as would be expected given that blocking GABA does not produce antinociception via a GPCR.

Rats were microinjected with vehicle or beta-CNA, followed by DERM-A594 into the vlPAG. A: Microinjection of DERM-A594 produced an increase in hot plate latency compared to baselines and this increase was blocked by pretreating rats with beta-CNA. B: The number of cells labeled with DERM-A594 (red) was assessed using confocal microscopy in the vlPAG at least 100 µm from the microinjection site. C: View of a single vlPAG neuron with DERM-A594 labeling. D: The number of DERM-A594 labeled neurons was decreased in rats pretreated with beta-CNA compared to saline-pretreated animals. E: Labeling for DERM-A594 from a representative animal pretreated with vehicle. F: Labeling for DERM-A594 from a representative animal pretreated with beta-CNA.