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Local and descending circuits regulate long-term potentiation and zif268 expression in spinal neurons.
Eur J Neurosci. 2006 Aug; 24(3):761-72.EJ

Abstract

Long-term potentiation (LTP), a use dependent long-lasting modification of synaptic strength, was first discovered in the hippocampus and later shown to occur in sensory areas of the spinal cord. Here we demonstrate that spinal LTP requires the activation of a subset of superficial spinal dorsal horn neurons expressing the neurokinin-1 receptor (NK1-R) that have previously been shown to mediate certain forms of hyperalgesia. These neurons participate in local spinal sensory processing, but are also the origin of a spino-bulbo-spinal loop driving a 5-hydroxytryptamine 3 receptor (5HT3-R)- mediated descending facilitation of spinal pain processing. Using a saporin-substance P conjugate to produce site-specific neuronal ablation, we demonstrate that NK1-R expressing cells in the superficial dorsal horn are crucial for the generation of LTP-like changes in neuronal excitability in deep dorsal horn neurons and this is modulated by descending 5HT3-R-mediated facilitatory controls. Hippocampal LTP is associated with early expression of the immediate-early gene zif268 and knockout of the gene leads to deficits in long-term LTP and learning and memory. We found that spinal LTP is also correlated with increased neuronal expression of zif268 in the superficial dorsal horn and that zif268 antisense treatment resulted in deficits in the long-term maintenance of inflammatory hyperalgesia. Our results support the suggestion that the generation of LTP in dorsal horn neurons following peripheral injury may be one mechanism whereby acute pain can be transformed into a long-term pain state.

Authors+Show Affiliations

Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

16930406

Citation

Rygh, Lars Jørgen, et al. "Local and Descending Circuits Regulate Long-term Potentiation and Zif268 Expression in Spinal Neurons." The European Journal of Neuroscience, vol. 24, no. 3, 2006, pp. 761-72.
Rygh LJ, Suzuki R, Rahman W, et al. Local and descending circuits regulate long-term potentiation and zif268 expression in spinal neurons. Eur J Neurosci. 2006;24(3):761-72.
Rygh, L. J., Suzuki, R., Rahman, W., Wong, Y., Vonsy, J. L., Sandhu, H., Webber, M., Hunt, S., & Dickenson, A. H. (2006). Local and descending circuits regulate long-term potentiation and zif268 expression in spinal neurons. The European Journal of Neuroscience, 24(3), 761-72.
Rygh LJ, et al. Local and Descending Circuits Regulate Long-term Potentiation and Zif268 Expression in Spinal Neurons. Eur J Neurosci. 2006;24(3):761-72. PubMed PMID: 16930406.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Local and descending circuits regulate long-term potentiation and zif268 expression in spinal neurons. AU - Rygh,Lars Jørgen, AU - Suzuki,Rie, AU - Rahman,Wahida, AU - Wong,Yuk, AU - Vonsy,Jean Laurent, AU - Sandhu,Hardip, AU - Webber,Mark, AU - Hunt,Stephen, AU - Dickenson,Anthony H, PY - 2006/8/26/pubmed PY - 2006/11/2/medline PY - 2006/8/26/entrez SP - 761 EP - 72 JF - The European journal of neuroscience JO - Eur. J. Neurosci. VL - 24 IS - 3 N2 - Long-term potentiation (LTP), a use dependent long-lasting modification of synaptic strength, was first discovered in the hippocampus and later shown to occur in sensory areas of the spinal cord. Here we demonstrate that spinal LTP requires the activation of a subset of superficial spinal dorsal horn neurons expressing the neurokinin-1 receptor (NK1-R) that have previously been shown to mediate certain forms of hyperalgesia. These neurons participate in local spinal sensory processing, but are also the origin of a spino-bulbo-spinal loop driving a 5-hydroxytryptamine 3 receptor (5HT3-R)- mediated descending facilitation of spinal pain processing. Using a saporin-substance P conjugate to produce site-specific neuronal ablation, we demonstrate that NK1-R expressing cells in the superficial dorsal horn are crucial for the generation of LTP-like changes in neuronal excitability in deep dorsal horn neurons and this is modulated by descending 5HT3-R-mediated facilitatory controls. Hippocampal LTP is associated with early expression of the immediate-early gene zif268 and knockout of the gene leads to deficits in long-term LTP and learning and memory. We found that spinal LTP is also correlated with increased neuronal expression of zif268 in the superficial dorsal horn and that zif268 antisense treatment resulted in deficits in the long-term maintenance of inflammatory hyperalgesia. Our results support the suggestion that the generation of LTP in dorsal horn neurons following peripheral injury may be one mechanism whereby acute pain can be transformed into a long-term pain state. SN - 0953-816X UR - https://www.unboundmedicine.com/medline/citation/16930406/Local_and_descending_circuits_regulate_long_term_potentiation_and_zif268_expression_in_spinal_neurons_ L2 - https://doi.org/10.1111/j.1460-9568.2006.04968.x DB - PRIME DP - Unbound Medicine ER -