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Selective ablation of dorsal horn NK1 expressing cells reveals a modulation of spinal alpha2-adrenergic inhibition of dorsal horn neurones.
Neuropharmacology. 2008 Jun; 54(8):1208-14.N

Abstract

Activity in descending systems from the brainstem modulates nociceptive transmission through the dorsal horn. Intrathecal injection of the neurotoxin saporin conjugated to SP (SP-SAP) into the lumbar spinal cord results in the selective ablation of NK(1) receptor expressing (NK(1)+ve) neurones in the superficial dorsal horn (lamina I/III). Loss of these NK(1)+ve neurones attenuates excitability of deep dorsal horn neurones due to a disruption of both intrinsic spinal circuits and a spino-bulbo-spinal loop, which activates a descending excitatory drive, mediated through spinal 5HT(3) receptors. Descending inhibitory pathways also modulate spinal activity and hence control the level of nociceptive transmission relayed to higher centres. To ascertain the spinal origins of the major descending noradrenergic inhibitory pathway we studied the effects of a selective alpha2-adrenoceptor antagonist, atipamezole, on neuronal activity in animals pre-treated with SP-SAP. Intrathecal application of atipamezole dose dependently facilitated the mechanically evoked neuronal responses of deep dorsal horn neurones to low intensity von Frey hairs (5-15 g) and noxious thermal (45-50 degrees C) evoked responses in SAP control animals indicating a physiological alpha2-adrenoceptor control. This facilitatory effect of atipamezole was lost in the SP-SAP treated group. These data suggest that activity within noradrenergic pathways have a dependence on dorsal horn NK(1)+ve cells. Further, noradrenergic descending inhibition may in part be driven by lamina I/III (NK(1)+ve) cells, and mediated via spinal alpha2-adrenoceptor activation. Since the same neuronal population drives descending facilitation and inhibition, the reduced excitability of lamina V/VI WDR neurones seen after loss of these NK(1)+ve neurones indicates a dominant role of descending facilitation.

Authors+Show Affiliations

Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK. w.rahman@ucl.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18462764

Citation

Rahman, Wahida, et al. "Selective Ablation of Dorsal Horn NK1 Expressing Cells Reveals a Modulation of Spinal Alpha2-adrenergic Inhibition of Dorsal Horn Neurones." Neuropharmacology, vol. 54, no. 8, 2008, pp. 1208-14.
Rahman W, Suzuki R, Hunt SP, et al. Selective ablation of dorsal horn NK1 expressing cells reveals a modulation of spinal alpha2-adrenergic inhibition of dorsal horn neurones. Neuropharmacology. 2008;54(8):1208-14.
Rahman, W., Suzuki, R., Hunt, S. P., & Dickenson, A. H. (2008). Selective ablation of dorsal horn NK1 expressing cells reveals a modulation of spinal alpha2-adrenergic inhibition of dorsal horn neurones. Neuropharmacology, 54(8), 1208-14. https://doi.org/10.1016/j.neuropharm.2008.03.014
Rahman W, et al. Selective Ablation of Dorsal Horn NK1 Expressing Cells Reveals a Modulation of Spinal Alpha2-adrenergic Inhibition of Dorsal Horn Neurones. Neuropharmacology. 2008;54(8):1208-14. PubMed PMID: 18462764.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Selective ablation of dorsal horn NK1 expressing cells reveals a modulation of spinal alpha2-adrenergic inhibition of dorsal horn neurones. AU - Rahman,Wahida, AU - Suzuki,Rie, AU - Hunt,Stephen P, AU - Dickenson,Anthony H, Y1 - 2008/04/08/ PY - 2007/11/27/received PY - 2008/03/20/revised PY - 2008/03/26/accepted PY - 2008/5/9/pubmed PY - 2008/8/30/medline PY - 2008/5/9/entrez SP - 1208 EP - 14 JF - Neuropharmacology JO - Neuropharmacology VL - 54 IS - 8 N2 - Activity in descending systems from the brainstem modulates nociceptive transmission through the dorsal horn. Intrathecal injection of the neurotoxin saporin conjugated to SP (SP-SAP) into the lumbar spinal cord results in the selective ablation of NK(1) receptor expressing (NK(1)+ve) neurones in the superficial dorsal horn (lamina I/III). Loss of these NK(1)+ve neurones attenuates excitability of deep dorsal horn neurones due to a disruption of both intrinsic spinal circuits and a spino-bulbo-spinal loop, which activates a descending excitatory drive, mediated through spinal 5HT(3) receptors. Descending inhibitory pathways also modulate spinal activity and hence control the level of nociceptive transmission relayed to higher centres. To ascertain the spinal origins of the major descending noradrenergic inhibitory pathway we studied the effects of a selective alpha2-adrenoceptor antagonist, atipamezole, on neuronal activity in animals pre-treated with SP-SAP. Intrathecal application of atipamezole dose dependently facilitated the mechanically evoked neuronal responses of deep dorsal horn neurones to low intensity von Frey hairs (5-15 g) and noxious thermal (45-50 degrees C) evoked responses in SAP control animals indicating a physiological alpha2-adrenoceptor control. This facilitatory effect of atipamezole was lost in the SP-SAP treated group. These data suggest that activity within noradrenergic pathways have a dependence on dorsal horn NK(1)+ve cells. Further, noradrenergic descending inhibition may in part be driven by lamina I/III (NK(1)+ve) cells, and mediated via spinal alpha2-adrenoceptor activation. Since the same neuronal population drives descending facilitation and inhibition, the reduced excitability of lamina V/VI WDR neurones seen after loss of these NK(1)+ve neurones indicates a dominant role of descending facilitation. SN - 0028-3908 UR - https://www.unboundmedicine.com/medline/citation/18462764/Selective_ablation_of_dorsal_horn_NK1_expressing_cells_reveals_a_modulation_of_spinal_alpha2_adrenergic_inhibition_of_dorsal_horn_neurones_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(08)00084-1 DB - PRIME DP - Unbound Medicine ER -