QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, February 8, 2006, 26(6):1833-1843; doi:10.1523/JNEUROSCI.4584-05.2006

This Article Full Text Full Text (PDF) Supplemental data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (13) Citing Articles via Google Scholar Google Scholar Articles by Torsney, C. Articles by MacDermott, A. B. Search for Related Content PubMed PubMed Citation Articles by Torsney, C. Articles by MacDermott, A. B. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Medline Plus Health Information Pain

 Previous Article  |  Next Article 

Cellular/Molecular
Disinhibition Opens the Gate to Pathological Pain Signaling in Superficial Neurokinin 1 Receptor-Expressing Neurons in Rat Spinal Cord

Carole Torsney¹ and Amy B. MacDermott^1,2

¹Department of Physiology and Cellular Biophysics and ²Center for Neurobiology and Behavior, Columbia University, New York, New York 10032

Correspondence should be addressed to Dr. Carole Torsney, Department of Physiology, Columbia University, 630 West 168th Street, New York, NY 10032. Email: ct2035{at}columbia.edu

Blockade of local spinal cord inhibition mimics the behavioral hypersensitivity that manifests in chronic pain states. This suggests that there is a pathway capable of mediating allodynia/hyperalgesia that exists but is normally under strong inhibitory control. Lamina I and III neurokinin 1 (NK1) receptor expressing (NK1R+) dorsal horn neurons, many of which are projection neurons, are required for the development of this hypersensitivity and are therefore likely to be a component of this proposed pathway. To investigate, whole-cell patch-clamp recordings were made from lamina I and III NK1R+ neurons in the spinal cord slice preparation with attached dorsal root. Excitatory postsynaptic currents were recorded in response to electrical stimulation of the dorsal root. Lamina I NK1R+ neurons were shown to receive high-threshold (A/C fiber) monosynaptic input, whereas lamina III NK1R+ neurons received low-threshold (A fiber) monosynaptic input. In contrast, lamina I neurons lacking NK1 receptor (NK1R–) received polysynaptic A fiber input. Blockade of local GABAergic and glycinergic inhibition with bicuculline (10 µM) and strychnine (300 nM), respectively, revealed significant A fiber input to lamina I NK1R+ neurons that was predominantly A fiber mediated. This novel A fiber input was polysynaptic in nature and required NMDA receptor activity to be functional. In lamina I NK1R– and lamina III NK1R+ neurons, disinhibition enhanced control-evoked responses, and this was also NMDA receptor dependent. These disinhibition-induced changes, in particular the novel polysynaptic low-threshold input onto lamina I NK1R+ neurons, may be an underlying component of the hypersensitivity present in chronic pain states.

Key words: nociceptors; dorsal horn; low threshold; primary afferent; NMDA receptor; inhibition

---

Received May 31, 2005; revised Dec. 18, 2005; accepted Dec. 19, 2005.

Correspondence should be addressed to Dr. Carole Torsney, Department of Physiology, Columbia University, 630 West 168th Street, New York, NY 10032. Email: ct2035{at}columbia.edu

This article has been cited by other articles:

				Y. Lu, J. Zheng, L. Xiong, M. Zimmermann, and J. Yang Spinal cord injury-induced attenuation of GABAergic inhibition in spinal dorsal horn circuits is associated with down-regulation of the chloride transporter KCC2 in rat J. Physiol., December 1, 2008; 586(23): 5701 - 5715. [Abstract] [Full Text] [PDF]

				R. A. Ingram, M. Fitzgerald, and M. L. Baccei Developmental Changes in the Fidelity and Short-Term Plasticity of GABAergic Synapses in the Neonatal Rat Dorsal Horn J Neurophysiol, June 1, 2008; 99(6): 3144 - 3150. [Abstract] [Full Text] [PDF]

				S. M. Geranton, C. Morenilla-Palao, and S. P. Hunt A Role for Transcriptional Repressor Methyl-CpG-Binding Protein 2 and Plasticity-Related Gene Serum- and Glucocorticoid-Inducible Kinase 1 in the Induction of Inflammatory Pain States J. Neurosci., June 6, 2007; 27(23): 6163 - 6173. [Abstract] [Full Text] [PDF]

				C.-K. Tong and A. B. MacDermott Both Ca2+-permeable and -impermeable AMPA receptors contribute to primary synaptic drive onto rat dorsal horn neurons J. Physiol., August 15, 2006; 575(1): 133 - 144. [Abstract] [Full Text] [PDF]

				E. Garcia-Nicas, J. M. A. Laird, and F. Cervero GABAA-Receptor Blockade Reverses the Injury-Induced Sensitization of Nociceptor-Specific (NS) Neurons in the Spinal Dorsal Horn of the Rat J Neurophysiol, August 1, 2006; 96(2): 661 - 670. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help