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This Article Full Text Full Text (PDF) Erratum (v575,p685) All Versions of this Article: 575/1/133    most recent jphysiol.2006.110072v1 Services Email this article to a friend Similar articles in this journal 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 Google Scholar Google Scholar Articles by Tong, C.-K. Articles by MacDermott, A. B. Search for Related Content PubMed PubMed Citation Articles by Tong, C.-K. Articles by MacDermott, A. B. Related Collections Neuroscience

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

Blockade of Ca²⁺-permeable AMPA receptors in the rat spinal cord diminishes the development of hyperalgesia and allodynia associated with peripheral injury. Cobalt uptake studies reveal that Ca²⁺-permeable AMPA receptors are expressed by some substance P receptor-expressing (NK1R+) neurons in lamina I, as well as other neurons throughout the superficial dorsal horn. Selective elimination of NK1R+ neurons in lamina I and lamina III/IV of the dorsal horn also suppresses development of hyperalgesia and allodynia. These observations raise the possibility that Ca²⁺-permeable AMPA receptors contribute to excitatory synaptic drive onto the NK1R+ neurons associated with allodynia and hyperalgesia. The first synapse in the pain pathway is the glutamatergic excitatory drive from the primary afferent fibres onto dorsal horn neurons. Therefore, we tested whether Ca²⁺-permeable AMPA receptors are located on lamina I and lamina III/IV NK1R+ neurons postsynaptic to primary afferent fibres, using inward rectification and polyamine toxins for receptor identification. We examined three different populations of dorsal horn neurons; lamina I NK1R+ neurons, including projection neurons, and non-NK1R+ (NK1R–) neurons including interneurons, and lamina III/IV NK1R+ neurons, believed to contribute to the low-threshold mechanosensory pathway. The majority of synapses in all three groups had rectification indices less than 1.0 and greater than 0.4, indicating that the AMPA receptors at these synapses are a mixture of Ca²⁺-permeable and -impermeable forms. Lamina III/IV NK1R+ neurons and lamina I NK1R– neurons have a significantly higher proportion of postsynaptic Ca²⁺-permeable AMPA receptors than lamina I NK1R+ neurons. Thus synaptically positioned Ca²⁺-permeable AMPA receptors directly contribute to low-threshold sensory afferent drive into the dorsal horn, and can mediate afferent input onto interneurons such as GABAergic neurons. These receptors also contribute to high-threshold primary afferent drive onto NK1R+ neurons in the superficial dorsal horn, but do so less consistently.

(Received 24 March 2006; accepted after revision 5 June 2006; first published online 8 June 2006)
Corresponding author C.-K. Tong: Department of Physiology and Cellular Biophysics, Columbia University, 630 W. 168th St, Room 1109, New York, NY 10032, USA. Email: ct433{at}columbia.edu

This article has been cited by other articles:

				K. S. Vikman, B. K. Rycroft, and M. J. Christie Switch to Ca2+-permeable AMPA and reduced NR2B NMDA receptor-mediated neurotransmission at dorsal horn nociceptive synapses during inflammatory pain in the rat J. Physiol., January 15, 2008; 586(2): 515 - 527. [Abstract] [Full Text] [PDF]

				Errata J. Physiol., September 1, 2006; 575(2): 685 - 685. [Full Text] [PDF]