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Effect of morphine on deep dorsal horn projection neurons depends on spinal GABAergic and glycinergic tone: implications for reduced opioid effect in neuropathic pain.
J Pharmacol Exp Ther. 2005 Nov; 315(2):696-703.JP

Abstract

The mu opioid agonist morphine has distinct effects on spinal dorsal horn neurons in the superficial and deep laminae. However, it is not clear if the inhibitory effect of morphine on dorsal horn projection neurons is secondary to its potentiating effect on inhibitory interneurons. In this study, we tested the hypothesis that removal of GABAergic and glycinergic inhibitory inputs attenuates the effect of morphine on dorsal horn projection neurons and the reduced spinal GABAergic tone contributes to attenuated morphine effect in neuropathic pain. Single-unit activity of deep dorsal horn projection neurons was recorded in anesthetized normal/sham controls and L(5) and L(6) spinal nerve-ligated rats. Spinal application of 10 microM morphine significantly inhibited the evoked responses of dorsal horn neurons in both normal/sham controls, and this effect was abolished by the specific mu opioid antagonist. However, the effect of morphine on dorsal horn projection neurons was significantly reduced in nerve-injured rats. Furthermore, topical application of the GABA(A) receptor antagonist bicuculline (20 microM) almost abolished the effect of morphine in normal/sham control rats but did not significantly attenuate the morphine effect in nerve-injured rats. On the other hand, the glycine receptor antagonist strychnine (4 microM) significantly decreased the effect of morphine in both nerve-injured and control animals. These data suggest that the inhibitory effect of opioids on dorsal horn projection neurons depends on GABAergic and glycinergic inputs. Furthermore, reduced GABAergic tone probably contributes to diminished analgesic effect of opioids in neuropathic pain.

Authors+Show Affiliations

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

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16033910

Citation

Chen, Yan-Ping, et al. "Effect of Morphine On Deep Dorsal Horn Projection Neurons Depends On Spinal GABAergic and Glycinergic Tone: Implications for Reduced Opioid Effect in Neuropathic Pain." The Journal of Pharmacology and Experimental Therapeutics, vol. 315, no. 2, 2005, pp. 696-703.
Chen YP, Chen SR, Pan HL. Effect of morphine on deep dorsal horn projection neurons depends on spinal GABAergic and glycinergic tone: implications for reduced opioid effect in neuropathic pain. J Pharmacol Exp Ther. 2005;315(2):696-703.
Chen, Y. P., Chen, S. R., & Pan, H. L. (2005). Effect of morphine on deep dorsal horn projection neurons depends on spinal GABAergic and glycinergic tone: implications for reduced opioid effect in neuropathic pain. The Journal of Pharmacology and Experimental Therapeutics, 315(2), 696-703.
Chen YP, Chen SR, Pan HL. Effect of Morphine On Deep Dorsal Horn Projection Neurons Depends On Spinal GABAergic and Glycinergic Tone: Implications for Reduced Opioid Effect in Neuropathic Pain. J Pharmacol Exp Ther. 2005;315(2):696-703. PubMed PMID: 16033910.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of morphine on deep dorsal horn projection neurons depends on spinal GABAergic and glycinergic tone: implications for reduced opioid effect in neuropathic pain. AU - Chen,Yan-Ping, AU - Chen,Shao-Rui, AU - Pan,Hui-Lin, Y1 - 2005/07/20/ PY - 2005/7/22/pubmed PY - 2006/1/13/medline PY - 2005/7/22/entrez SP - 696 EP - 703 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 315 IS - 2 N2 - The mu opioid agonist morphine has distinct effects on spinal dorsal horn neurons in the superficial and deep laminae. However, it is not clear if the inhibitory effect of morphine on dorsal horn projection neurons is secondary to its potentiating effect on inhibitory interneurons. In this study, we tested the hypothesis that removal of GABAergic and glycinergic inhibitory inputs attenuates the effect of morphine on dorsal horn projection neurons and the reduced spinal GABAergic tone contributes to attenuated morphine effect in neuropathic pain. Single-unit activity of deep dorsal horn projection neurons was recorded in anesthetized normal/sham controls and L(5) and L(6) spinal nerve-ligated rats. Spinal application of 10 microM morphine significantly inhibited the evoked responses of dorsal horn neurons in both normal/sham controls, and this effect was abolished by the specific mu opioid antagonist. However, the effect of morphine on dorsal horn projection neurons was significantly reduced in nerve-injured rats. Furthermore, topical application of the GABA(A) receptor antagonist bicuculline (20 microM) almost abolished the effect of morphine in normal/sham control rats but did not significantly attenuate the morphine effect in nerve-injured rats. On the other hand, the glycine receptor antagonist strychnine (4 microM) significantly decreased the effect of morphine in both nerve-injured and control animals. These data suggest that the inhibitory effect of opioids on dorsal horn projection neurons depends on GABAergic and glycinergic inputs. Furthermore, reduced GABAergic tone probably contributes to diminished analgesic effect of opioids in neuropathic pain. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/16033910/Effect_of_morphine_on_deep_dorsal_horn_projection_neurons_depends_on_spinal_GABAergic_and_glycinergic_tone:_implications_for_reduced_opioid_effect_in_neuropathic_pain_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=16033910 DB - PRIME DP - Unbound Medicine ER -