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Cyclic GMP pathway is critical for inducing long–term sensitization of nociceptive sensory neurons

Nature Neuroscience volume 2, pages 18–23 (1999)Cite this article

Abstract

Noxious stimulation can trigger persistent sensitization of somatosensory systems that involves memory–like mechanisms. Here we report that noxious stimulation of the mollusc Aplysia produces transcription–dependent, long–term hyperexcitability (LTH) of nociceptive sensory neurons that requires a nitric oxide (NO)–cyclic GMP–protein kinase G (PKG) pathway. Injection of cGMP induced LTH, whereas antagonists of the NO–cGMP–PKG pathway prevented pinch–induced LTH. Co–injection of calcium/cAMP–responsive–element (CRE) blocked both pinch–induced LTH and cAMP–induced LTH, but antagonists of protein kinase A (PKA) failed to block pinch–induced LTH. Thus the NO–cGMP–PKG pathway and at least one other pathway, but not the cAMP–PKA pathway, are critical for inducing LTH after brief, noxious stimulation.

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Figure 1: Injection of cyclic GMP induces long–term hyperexcitability (LTH).
Figure 2: Comparison of LTH induced by injection of cGMP and cAMP.
Figure 3: LTH induced by cGMP injection requires macromolecular synthesis that is independent of CREB activity.
Figure 4: NO–cGMP–PKG pathway and a CREB–dependent pathway, but not PKA, are required for induction of LTH by brief noxious stimulation.

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Acknowledgements

This work was supported by grants NS35979 and NS35882 from the National Institute for Neurological Disorders and Stroke. We thank R.T. Ambron, P.T. Kelly, X. Liao, and F. Murad for suggestions, and C. Brou and G. Rumbly for assistance.

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  1. Department of Integrative Biology, Physiology and Pharmacology, University of Texas–Houston, 6431 Fannin St., Houston, 77030, Texas, USA

    Matthew R. Lewin & Edgar T. Walters

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Correspondence to Edgar T. Walters.

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Lewin, M., Walters, E. Cyclic GMP pathway is critical for inducing long–term sensitization of nociceptive sensory neurons. Nat Neurosci 2, 18–23 (1999). https://doi.org/10.1038/4520

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