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Spinal nerve ligation increases alpha2-adrenergic receptor G-protein coupling in the spinal cord.
Brain Res. 2005 Mar 15; 1038(1):76-82.BR

Abstract

Intrathecal and epidural administration of the alpha2-adrenergic receptor agonist clonidine in humans results in analgesia to both acute nociceptive and chronic neuropathic pain. The potency of clonidine increases with hypersensitivity to mechanical stimuli after nerve injury, although the reasons for this change are unknown. In the present study, we tested the hypothesis that peripheral nerve injury alters either spinal alpha2-adrenergic receptor-mediated G-protein activity or alpha2-adrenergic receptor number. Rats were randomized to left spinal nerve ligation (SNL) or sham surgery. Tactile hypersensitivity in the hindpaw was confirmed and lumbar spinal cords were removed for binding assays. To examine agonist-induced G-protein coupling, [35S]GTP gamma S binding experiments were performed in spinal cord membranes and sections using norepinephrine as an alpha2-adrenergic agonist. SNL was associated with an increase in maximal efficacy, but not potency, of norepinephrine-stimulated [35S]GTP gamma S binding in dorsal horn. SNL had no effect on basal [35S]GTP gamma S binding or on muscarinic cholinergic-stimulated [35S]GTP gamma S binding. [35S]GTP gamma S autoradiography showed that this increase in alpha2-adrenergic-activated G-proteins occurred both ipsilateral and contralateral to SNL surgery. SNL did not alter total alpha2-adrenergic receptor number or affinity to [3H]-rauwolscine binding, and displacement studies with the alpha2A-adrenergic antagonist BRL44408 revealed that most of the binding was associated with the alpha2A-adrenergic subtype. These data suggest that the increased potency of clonidine in neuropathic pain could reflect increased efficiency of G-protein coupling from spinal alpha2-adrenergic receptors.

Authors+Show Affiliations

Department of Anesthesiology, University of Munster, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15748875

Citation

Bantel, Carsten, et al. "Spinal Nerve Ligation Increases Alpha2-adrenergic Receptor G-protein Coupling in the Spinal Cord." Brain Research, vol. 1038, no. 1, 2005, pp. 76-82.
Bantel C, Eisenach JC, Duflo F, et al. Spinal nerve ligation increases alpha2-adrenergic receptor G-protein coupling in the spinal cord. Brain Res. 2005;1038(1):76-82.
Bantel, C., Eisenach, J. C., Duflo, F., Tobin, J. R., & Childers, S. R. (2005). Spinal nerve ligation increases alpha2-adrenergic receptor G-protein coupling in the spinal cord. Brain Research, 1038(1), 76-82.
Bantel C, et al. Spinal Nerve Ligation Increases Alpha2-adrenergic Receptor G-protein Coupling in the Spinal Cord. Brain Res. 2005 Mar 15;1038(1):76-82. PubMed PMID: 15748875.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Spinal nerve ligation increases alpha2-adrenergic receptor G-protein coupling in the spinal cord. AU - Bantel,Carsten, AU - Eisenach,James C, AU - Duflo,Frederic, AU - Tobin,Joseph R, AU - Childers,Steven R, PY - 2004/08/17/received PY - 2004/12/31/revised PY - 2005/01/04/accepted PY - 2005/3/8/pubmed PY - 2005/9/13/medline PY - 2005/3/8/entrez SP - 76 EP - 82 JF - Brain research JO - Brain Res. VL - 1038 IS - 1 N2 - Intrathecal and epidural administration of the alpha2-adrenergic receptor agonist clonidine in humans results in analgesia to both acute nociceptive and chronic neuropathic pain. The potency of clonidine increases with hypersensitivity to mechanical stimuli after nerve injury, although the reasons for this change are unknown. In the present study, we tested the hypothesis that peripheral nerve injury alters either spinal alpha2-adrenergic receptor-mediated G-protein activity or alpha2-adrenergic receptor number. Rats were randomized to left spinal nerve ligation (SNL) or sham surgery. Tactile hypersensitivity in the hindpaw was confirmed and lumbar spinal cords were removed for binding assays. To examine agonist-induced G-protein coupling, [35S]GTP gamma S binding experiments were performed in spinal cord membranes and sections using norepinephrine as an alpha2-adrenergic agonist. SNL was associated with an increase in maximal efficacy, but not potency, of norepinephrine-stimulated [35S]GTP gamma S binding in dorsal horn. SNL had no effect on basal [35S]GTP gamma S binding or on muscarinic cholinergic-stimulated [35S]GTP gamma S binding. [35S]GTP gamma S autoradiography showed that this increase in alpha2-adrenergic-activated G-proteins occurred both ipsilateral and contralateral to SNL surgery. SNL did not alter total alpha2-adrenergic receptor number or affinity to [3H]-rauwolscine binding, and displacement studies with the alpha2A-adrenergic antagonist BRL44408 revealed that most of the binding was associated with the alpha2A-adrenergic subtype. These data suggest that the increased potency of clonidine in neuropathic pain could reflect increased efficiency of G-protein coupling from spinal alpha2-adrenergic receptors. SN - 0006-8993 UR - https://www.unboundmedicine.com/medline/citation/15748875/Spinal_nerve_ligation_increases_alpha2_adrenergic_receptor_G_protein_coupling_in_the_spinal_cord_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(05)00066-1 DB - PRIME DP - Unbound Medicine ER -