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Superficial NK1 expressing spinal dorsal horn neurones modulate inhibitory neurotransmission mediated by spinal GABA(A) receptors.
Neurosci Lett. 2007 Jun 04; 419(3):278-83.NL

Abstract

Lamina 1 projection neurones which express the NK1 receptor (NK1R+) drive a descending serotonergic pathway from the brainstem that enhances spinal dorsal horn neuronal activity via the facilitatory spinal 5-HT3 receptor. Selective destruction of these cells via lumbar injection of substance P-saporin (SP-SAP) attenuates pain behaviours, including mechanical and thermal hypersensitivity, which are mirrored by deficits in the evoked responses of lamina V-VI wide dynamic range (WDR) neurones to noxious stimuli. To assess whether removing the origin of this facilitatory spino-bulbo-spinal loop results in alterations in GABAergic spinal inhibitory systems, the effects of spinal bicuculline, a selective GABA(A) receptor antagonist, on the evoked neuronal responses to electrical (Abeta-, Adelta-, C-fibre, post-discharge and Input) and mechanical (brush, prod and von Frey (vF) 8 and 26 g) stimuli were measured in SAP and SP-SAP groups. In the SAP control group, bicuculline produced a significant dose related facilitation of the electrically evoked Adelta-, C-fibre, post-discharge and input neuronal responses. The evoked mechanical (prod, vF8 g and 26 g) responses were also significantly increased. Brush evoked neuronal responses in these animals were enhanced but did not reach significance. This facilitatory effect of bicuculline, however, was lost in the SP-SAP treated group. The generation of intrinsic GABAergic transmission in the spinal cord appears dependent on NK1 bearing neurons, yet despite the loss of GABAergic inhibitory controls after SP-SAP treatment, the net effect is a decrease in spinal cord excitability. Thus activation of these cells predominantly drives 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 availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

17493751

Citation

Rahman, Wahida, et al. "Superficial NK1 Expressing Spinal Dorsal Horn Neurones Modulate Inhibitory Neurotransmission Mediated By Spinal GABA(A) Receptors." Neuroscience Letters, vol. 419, no. 3, 2007, pp. 278-83.
Rahman W, Sikandar S, Sikander S, et al. Superficial NK1 expressing spinal dorsal horn neurones modulate inhibitory neurotransmission mediated by spinal GABA(A) receptors. Neurosci Lett. 2007;419(3):278-83.
Rahman, W., Sikandar, S., Sikander, S., Suzuki, R., Hunt, S. P., & Dickenson, A. H. (2007). Superficial NK1 expressing spinal dorsal horn neurones modulate inhibitory neurotransmission mediated by spinal GABA(A) receptors. Neuroscience Letters, 419(3), 278-83.
Rahman W, et al. Superficial NK1 Expressing Spinal Dorsal Horn Neurones Modulate Inhibitory Neurotransmission Mediated By Spinal GABA(A) Receptors. Neurosci Lett. 2007 Jun 4;419(3):278-83. PubMed PMID: 17493751.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Superficial NK1 expressing spinal dorsal horn neurones modulate inhibitory neurotransmission mediated by spinal GABA(A) receptors. AU - Rahman,Wahida, AU - Sikandar,Shafaq, AU - Sikander,Shafaq, AU - Suzuki,Rie, AU - Hunt,Stephen P, AU - Dickenson,Anthony H, Y1 - 2007/04/22/ PY - 2007/03/01/received PY - 2007/04/18/revised PY - 2007/04/19/accepted PY - 2007/5/12/pubmed PY - 2007/9/29/medline PY - 2007/5/12/entrez SP - 278 EP - 83 JF - Neuroscience letters JO - Neurosci. Lett. VL - 419 IS - 3 N2 - Lamina 1 projection neurones which express the NK1 receptor (NK1R+) drive a descending serotonergic pathway from the brainstem that enhances spinal dorsal horn neuronal activity via the facilitatory spinal 5-HT3 receptor. Selective destruction of these cells via lumbar injection of substance P-saporin (SP-SAP) attenuates pain behaviours, including mechanical and thermal hypersensitivity, which are mirrored by deficits in the evoked responses of lamina V-VI wide dynamic range (WDR) neurones to noxious stimuli. To assess whether removing the origin of this facilitatory spino-bulbo-spinal loop results in alterations in GABAergic spinal inhibitory systems, the effects of spinal bicuculline, a selective GABA(A) receptor antagonist, on the evoked neuronal responses to electrical (Abeta-, Adelta-, C-fibre, post-discharge and Input) and mechanical (brush, prod and von Frey (vF) 8 and 26 g) stimuli were measured in SAP and SP-SAP groups. In the SAP control group, bicuculline produced a significant dose related facilitation of the electrically evoked Adelta-, C-fibre, post-discharge and input neuronal responses. The evoked mechanical (prod, vF8 g and 26 g) responses were also significantly increased. Brush evoked neuronal responses in these animals were enhanced but did not reach significance. This facilitatory effect of bicuculline, however, was lost in the SP-SAP treated group. The generation of intrinsic GABAergic transmission in the spinal cord appears dependent on NK1 bearing neurons, yet despite the loss of GABAergic inhibitory controls after SP-SAP treatment, the net effect is a decrease in spinal cord excitability. Thus activation of these cells predominantly drives facilitation. SN - 0304-3940 UR - https://www.unboundmedicine.com/medline/citation/17493751/Superficial_NK1_expressing_spinal_dorsal_horn_neurones_modulate_inhibitory_neurotransmission_mediated_by_spinal_GABA_A__receptors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(07)00483-1 DB - PRIME DP - Unbound Medicine ER -