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Abstract:
Clinical pain is previous termanext term serious public health issue. Treatment of pain-related suffering requires knowledge of how pain signals are initially interpreted and subsequently transmitted and perpetuated. This review article is one of three reviews in this issue of Neuron that address our understanding of the pain process and possible solutions to the problem from both cellular- and systems-level viewpoints.
The electrophysiological properties of peripheral neurons activated by noxious stimuli, the primary afferent previous termnociceptors,next term have been investigated intensively, and our knowledge about the molecular basis of transducers for noxious stimuli has increased greatly. In contrast, understanding of the intracellular previous termsignalingnext term mechanisms regulating previous termnociceptor sensitizationnext term downstream of ligand binding to the receptors is still at previous termanext term relatively nascent stage. After outlining the initiated previous termsignalingnext term cascades, we discuss the emerging plasticity within these cascades and the importance of subcellular compartmentalization. In addition, the recently realized importance of functional interactions with the extracellular matrix, cytoskeleton, intracellular organelles such as mitochondria, and sex hormones will be introduced. This burgeoning literature establishes new cellular features crucial for the function of nociceptive neurons and argues that additional focus should be placed on understanding the complex integration of cellular events that make up the “previous termcell biologynext term of pain.”
