Role of spinal nitric oxide in the inhibitory effect of [D-Pen2, D-Pen5]-enkephalin on ascending dorsal horn neurons in normal and diabetic rats.
Intrathecal [D-Pen2,D-Pen5]-enkephalin (DPDPE; a delta-opioid agonist) has a profound antinociceptive effect in neuropathic pain. Spinal nitric oxide (NO) has been implicated in the analgesic effect of several G protein-coupled receptor agonists. Little, however, is known about the role of spinal NO in the inhibitory effect of DPDPE on spinal dorsal horn neurons. In the present study, we determined the role of NO in the inhibitory effect of DPDPE on ascending dorsal horn neurons in normal rats and in a rat model of diabetic neuropathic pain. Single-unit activity of ascending dorsal horn neurons was recorded in anesthetized rats. The responses of dorsal horn neurons to graded mechanical stimuli and von Frey filaments were determined before and after local spinal application of 0.1 to 5 microM DPDPE. The influence of an NO synthase inhibitor, 1-(2-trifluoromethylphenyl) imidazole (TRIM; 30 microM), on the effect of DPDPE was then studied in separate groups of dorsal horn neurons in normal and diabetic rats. DPDPE inhibited the response of dorsal horn neurons in both normal and diabetic rats in a concentration-dependent fashion. The inhibitory effect of 1 microM DPDPE was abolished by 1 microM naltrindole, a delta-opioid antagonist. Furthermore, the inhibitory effect of DPDPE on the evoked response of dorsal horn neurons was largely eliminated by TRIM in normal and diabetic rats. These data suggest that DPDPE has a profound inhibitory effect on dorsal horn neurons in normal and diabetic rats. Spinal endogenous NO is essential for the inhibitory effect of DPDPE on ascending dorsal horn neurons in both normal and diabetic rats.
Khan
Ghous M
GM
Department of Anesthesiology, Penn State University College of Medicine, Hershey, Pennsylvania 17033, USA.
Li
De-Pei
DP
Chen
Shao-Rui
SR
Pan
Hui-Lin
HL
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000201:enzymology; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000008:administration & dosage / Q000494:pharmacology*; D007278:Injections, Spinal; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000502:physiology
D017465:Receptors, Opioid, delta; D009569:Nitric Oxide; D020881:Enkephalin, D-Penicillamine (2,5)-; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat