Tags

Type your tag names separated by a space and hit enter

Inhibition of glutamatergic synaptic input to spinal lamina II(o) neurons by presynaptic alpha(2)-adrenergic receptors.
J Neurophysiol. 2002 Apr; 87(4):1938-47.JN

Abstract

Activation of spinal alpha(2)-adrenergic receptors by the descending noradrenergic system and alpha(2)-adrenergic agonists produces analgesia. However, the sites and mechanisms of the analgesic action of spinally administered alpha(2)-adrenergic receptor agonists such as clonidine are not fully known. The dorsal horn neurons in the outer zone of lamina II (lamina II(o)) are important for processing nociceptive information from C-fiber primary afferents. In the present study, we tested a hypothesis that activation of presynaptic alpha(2)-adrenergic receptors by clonidine inhibits the excitatory synaptic input to lamina II(o) neurons. Whole cell voltage-clamp recordings were performed on visualized lamina II(o) neurons in the spinal cord slice of rats. The miniature excitatory postsynaptic currents (mEPSCs) were recorded in the presence of tetrodotoxin, bicuculline, and strychnine. The evoked EPSCs were obtained by electrical stimulation of the dorsal root entry zone or the attached dorsal root. Both mEPSCs and evoked EPSCs were abolished by application of 6-cyano-7-nitroquinoxaline-2,3-dione. Clonidine (10 microM) significantly decreased the frequency of mEPSCs from 5.8 +/- 0.9 to 2.7 +/- 0.6 Hz (means +/- SE) without altering the amplitude and the decay time constant of mEPSCs in 25 of 27 lamina II(o) neurons. Yohimbine (2 microM, an alpha(2)-adrenergic receptor antagonist), but not prazosin (2 microM, an alpha(1)-adrenergic receptor antagonist), blocked the inhibitory effect of clonidine on the mEPSCs. Clonidine (1-20 microM, n = 8) also significantly attenuated the peak amplitude of evoked EPSCs in a concentration-dependent manner. The effect of clonidine on evoked EPSCs was abolished in the presence of yohimbine (n = 5). These data suggest that clonidine inhibits the excitatory synaptic input to lamina II(o) neurons through activation of alpha(2)-adrenergic receptors located on the glutamatergic afferent terminals. Presynaptic inhibition of glutamate release from primary afferents onto lamina II(o) neurons likely plays an important role in the analgesic action produced by activation of the descending noradrenergic system and alpha(2)-adrenergic agonists.

Authors+Show Affiliations

Department of Anesthesiology, Penn State University College of Medicine, Hershey, Pennsylvania 17033-0850, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11929913

Citation

Pan, Yu-Zhen, et al. "Inhibition of Glutamatergic Synaptic Input to Spinal Lamina II(o) Neurons By Presynaptic Alpha(2)-adrenergic Receptors." Journal of Neurophysiology, vol. 87, no. 4, 2002, pp. 1938-47.
Pan YZ, Li DP, Pan HL. Inhibition of glutamatergic synaptic input to spinal lamina II(o) neurons by presynaptic alpha(2)-adrenergic receptors. J Neurophysiol. 2002;87(4):1938-47.
Pan, Y. Z., Li, D. P., & Pan, H. L. (2002). Inhibition of glutamatergic synaptic input to spinal lamina II(o) neurons by presynaptic alpha(2)-adrenergic receptors. Journal of Neurophysiology, 87(4), 1938-47.
Pan YZ, Li DP, Pan HL. Inhibition of Glutamatergic Synaptic Input to Spinal Lamina II(o) Neurons By Presynaptic Alpha(2)-adrenergic Receptors. J Neurophysiol. 2002;87(4):1938-47. PubMed PMID: 11929913.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of glutamatergic synaptic input to spinal lamina II(o) neurons by presynaptic alpha(2)-adrenergic receptors. AU - Pan,Yu-Zhen, AU - Li,De-Pei, AU - Pan,Hui-Lin, PY - 2002/4/4/pubmed PY - 2002/6/13/medline PY - 2002/4/4/entrez SP - 1938 EP - 47 JF - Journal of neurophysiology JO - J. Neurophysiol. VL - 87 IS - 4 N2 - Activation of spinal alpha(2)-adrenergic receptors by the descending noradrenergic system and alpha(2)-adrenergic agonists produces analgesia. However, the sites and mechanisms of the analgesic action of spinally administered alpha(2)-adrenergic receptor agonists such as clonidine are not fully known. The dorsal horn neurons in the outer zone of lamina II (lamina II(o)) are important for processing nociceptive information from C-fiber primary afferents. In the present study, we tested a hypothesis that activation of presynaptic alpha(2)-adrenergic receptors by clonidine inhibits the excitatory synaptic input to lamina II(o) neurons. Whole cell voltage-clamp recordings were performed on visualized lamina II(o) neurons in the spinal cord slice of rats. The miniature excitatory postsynaptic currents (mEPSCs) were recorded in the presence of tetrodotoxin, bicuculline, and strychnine. The evoked EPSCs were obtained by electrical stimulation of the dorsal root entry zone or the attached dorsal root. Both mEPSCs and evoked EPSCs were abolished by application of 6-cyano-7-nitroquinoxaline-2,3-dione. Clonidine (10 microM) significantly decreased the frequency of mEPSCs from 5.8 +/- 0.9 to 2.7 +/- 0.6 Hz (means +/- SE) without altering the amplitude and the decay time constant of mEPSCs in 25 of 27 lamina II(o) neurons. Yohimbine (2 microM, an alpha(2)-adrenergic receptor antagonist), but not prazosin (2 microM, an alpha(1)-adrenergic receptor antagonist), blocked the inhibitory effect of clonidine on the mEPSCs. Clonidine (1-20 microM, n = 8) also significantly attenuated the peak amplitude of evoked EPSCs in a concentration-dependent manner. The effect of clonidine on evoked EPSCs was abolished in the presence of yohimbine (n = 5). These data suggest that clonidine inhibits the excitatory synaptic input to lamina II(o) neurons through activation of alpha(2)-adrenergic receptors located on the glutamatergic afferent terminals. Presynaptic inhibition of glutamate release from primary afferents onto lamina II(o) neurons likely plays an important role in the analgesic action produced by activation of the descending noradrenergic system and alpha(2)-adrenergic agonists. SN - 0022-3077 UR - https://www.unboundmedicine.com/medline/citation/11929913/Inhibition_of_glutamatergic_synaptic_input_to_spinal_lamina_II_o__neurons_by_presynaptic_alpha_2__adrenergic_receptors_ L2 - http://www.physiology.org/doi/full/10.1152/jn.00575.2001?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -