RT Journal Article
SR Electronic
T1 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
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1021
OP 1028
DO 10.1124/jpet.102.040865
VO 303
IS 3
A1 Ghous M. Khan
A1 De-Pei Li
A1 Shao-Rui Chen
A1 Hui-Lin Pan
YR 2002
UL http://jpet.aspetjournals.org/content/303/3/1021.abstract
AB Intrathecal [d-Pen2,d-Pen5]-enkephalin (DPDPE; a δ-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 μM DPDPE. The influence of an NO synthase inhibitor, 1-(2-trifluoromethylphenyl) imidazole (TRIM; 30 μM), 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 μM DPDPE was abolished by 1 μM naltrindole, a δ-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.