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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.
J Pharmacol Exp Ther. 2002 Dec; 303(3):1021-8.JP

Abstract

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.

Authors+Show Affiliations

Department of Anesthesiology, Penn State University College of Medicine, Hershey, Pennsylvania 17033, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12438523

Citation

Khan, Ghous M., et al. "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." The Journal of Pharmacology and Experimental Therapeutics, vol. 303, no. 3, 2002, pp. 1021-8.
Khan GM, Li DP, Chen SR, et al. 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. J Pharmacol Exp Ther. 2002;303(3):1021-8.
Khan, G. M., Li, D. P., Chen, S. R., & Pan, H. L. (2002). 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. The Journal of Pharmacology and Experimental Therapeutics, 303(3), 1021-8.
Khan GM, et al. 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. J Pharmacol Exp Ther. 2002;303(3):1021-8. PubMed PMID: 12438523.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR 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. AU - Khan,Ghous M, AU - Li,De-Pei, AU - Chen,Shao-Rui, AU - Pan,Hui-Lin, PY - 2002/11/20/pubmed PY - 2002/12/27/medline PY - 2002/11/20/entrez SP - 1021 EP - 8 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 303 IS - 3 N2 - 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. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/12438523/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_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=12438523 DB - PRIME DP - Unbound Medicine ER -