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Understanding the anatomy and physiology of pain transmission systems is important for the pain management specialist because it informs diagnostic and treatment decisions for the common pain syndromes for which patients seek help (e.g., diabetic neuropathy and migraine headache). Interventions to provide the relief the patient seeks (nerve blocks, implantable devices) are available at distinct anatomic sites. As ongoing research reveals new modalities and pharmaceutical agents to provide relief, the provider with this knowledge base will better understand their mechanism and application. Designed as an overview to be read in one sitting, the clinician will find it an efficient way to review the large body of knowledge acquired in medical school and residency.

This chapter reviews the transmission of a nociceptive or pain impulse from the site of stimulus in the periphery to the central nervous system. The basic anatomic pathways of nociceptive transmission and of descending nociceptive modulations are described. While some basic physiology is discussed, the fundamentals of neuronal transduction, such as action potential propagation and the relationship of the cell body to the dendrites and axon, are not. While mention is made here of pathophysiology and disease states, the details follow in the subsequent chapters.

This chapter focuses on the neuronal components of the nervous system that transmit and modulate nociceptive stimuli. Although attention is focused on primary afferents and descending pathways, interneurons in the dorsal horn of the spinal cord and at higher levels in the central nervous system play important roles in signal processing, transmission, plasticity, and, ultimately, in the way pain is experienced, including its emotional components. The complexities of chronic pain syndromes, including such theories as chronic pain as a variant of depressive disorders,1,2 are discussed elsewhere.

Knowledge of nociceptive transmission has advanced considerably since Descartes outlined his concept of the nerve as tubes with delicate threads to convey a painful impulse.3 It is now widely believed that stimulation of a primary afferent neuron in the peripheral nervous system results in patterns of activation of neurons in the dorsal horn of the spinal cord and then in transmission(s) rostrally to the brain.


Sensory neurons, called primary afferents, have a cell body in the dorsal root ganglia (DRG) of the spinal cord or in the ganglia of the cranial nerves. Cranial nerves V, VII, IX, and X receive inputs from primary afferents and, thus, sensory information from the head, face, and throat. Nerve cells in the DRG are a heterogeneous population of size and function—a reflection of the heterogeneity of the sensory inputs processed by the central nervous system.4 Central nervous system pain processing is also influenced by immune and surrounding glial cells.5

The classic nomenclature of peripheral neurons relies on the size of the axon and presence or absence of myelin as distinguishing characteristics. This taxonomy ...

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