Skip to Main Content


Optimal postoperative pain management is a clinical priority because poorly managed pain may delay functional recovery from surgery and /or lead to chronic pain.1 Nevertheless, despite considerable effort to improve postoperative pain management, one third of patients continue to suffer from moderate to severe pain.2 The lack of consistently effective analgesics devoid of deleterious consequences remains one of the main causes of the inadequacy of postoperative pain management. Therefore, identification of novel therapeutic targets and more effective management strategies remain high priorities in pain research.

To provide a framework to facilitate understanding of the mechanisms underlying the efficacy of currently available pain management strategies, at least some of the reasons for the failure to achieve adequate pain relief, as well as identify viable targets for future interventions, this chapter covers fundamental neurobiologic mechanisms of the nociceptive system. Given space constraints, and the fact the functional alterations of the nociceptive system in the context of chronic pain are addressed in more detail in subsequent chapters, this issue will be not be discussed at length here.


Overview of Nociceptive/Pain Pathway

The simplest depiction of the neural circuit underlying the perception of pain in response to noxious or potentially tissue damaging stimulation of peripheral tissue involves three neurons. The first is a nociceptor, a specialized primary afferent neuron with a peripheral terminal innervating the site of stimulation, a cell body in a spinal or dorsal root ganglia or trigeminal ganglia, and a central terminal in the spinal cord or brainstem dorsal horn. The second is an “output,” or projection, neuron in the spinal cord/trigeminal dorsal horn that receives input from the nociceptor and projects to the thalamus. And the third neuron projects from the thalamus to the sensory cortex. But as a sensory and emotional experience that is highly motivational (i.e., withdrawal/escape), pain necessarily involves far more than three neurons. This point is further underscored when one considers the heterogeneity of the pain experience which varies in intensity, quality, duration, location, emotional valence, whether it is evoked or ongoing, and so on.

The integration of nociceptive information in supraspinal regions leads to complex sensory, emotional, and motivational components that make up the perception of pain. Ascending sensory information reaches many cortical sites via parallel pathways. Along the way, however, this information also impinges upon subcortical and brainstem sites that underlie coordinated physiologic responses required for “fight or flight” as well as the modulation of the ascending nociceptive signal. Projections from the brainstem to the spinal cord are referred to as descending modulations. These sites may also be accessed via therapeutic interventions to block or attenuate pain (Figure 73–1, Table 73–1).

Figure 73–1.

Overview of nociceptive pain pathway. Major structures in ascending and descending nociceptive pathway. Ascending: primary afferent fibers provide nociceptive input to the spinal cord, which ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.