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Second Messenger Pathways in Pain

  • Chapter
Molecular Pain

Abstract

G protein-coupled (GPCRs) and ionotropic receptors play an important role in normal and pathological pain transmission and modulation. Activation of these receptors either directly or indirectly further activates intracellular second messenger pathways to enhance or suppress nociceptive processing. These second messenger pathways are important both in the periphery as well as in the central nervous system in mediating pain states. Major second messengers associated with GPCRs are cAMP, cGMP, inositol triphosphate (IP3), Ca2+and diacylglyceride (DAG). These second messengers transmit the signals mainly by activating protein kinases, such as protein kinase A (by cAMP), protein kinase G (by cGMP), and protein kinase C (by DAG/ IP3). Ionotropic receptors also activate components of second messenger systems by increasing calcium influx. Preclinical data show that peripheral injury or inflammation activates cAMP-protein kinase A (PKA) and/ or DAG/IP3-PKC cascade in the periphery and/ or central nervous system (CNS), which leads to pain. The cyclic GMP-PKG system has been shown to either facilitate or inhibit nociception. However, the exact role of the cGMP-PKG pathway in nociception is unclear at this point, although there is sufficient evidence to show its involvement in the modulation of nociception. Experimental evidences suggest that, despite the ubiquitous distribution of these pathways throughout living cells, their selective modullation could lead to novel therapies in pain conditions.

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  1. Graduate Program in Physical Therapy & Rehabilitation Science University of Iowa, 1-242 Medical Education Building Iowa City, Iowa, 52242-1190, USA

    Kathleen A. Sluka PT, PhD (Associate Professor)

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  1. Department of Physiology, University of Toronto, Medical Sciences Bldg, Rm 3342 1 King’s College Circle, Toronto, Ontario, Canada, M5S 1A8

    Min Zhuo

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Sluka, K.A., Skyba, D.A., Hoeger Bement, M.K., Audette, K.M., Radhakrishnan, R. (2007). Second Messenger Pathways in Pain. In: Zhuo, M. (eds) Molecular Pain. Springer, New York, NY. https://doi.org/10.1007/978-0-387-75269-3_17

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