Definition of pain 

Perception and modulation of pain 

Referred pain 

Peripheral nociceptive system

Nociceptive receptors are defined as nerve endings that are sensitive to noxious or potentially noxious (mechanical and chemical) stimuli. The perceptual aspect of the nociceptive system consists of unmyelinated free nerve endings, distributed three dimensionally throughout skin, subcutaneous and adipose tissue, fasciae, aponeuroses, ligaments, tendons, muscles, periosteum and bone.6,7 Clinically, three distinct areas of pain perception may be considered: the skin (superficial somatic pain); the locomotor system (deep somatic pain); and the viscera (visceral pain). Of these, only the skin is adapted to localize pain exactly in the region of injury. Deep somatic and visceral pain are often felt in unusual locations (see Referred pain, p. 6).

In normal circumstances, this nociceptive receptor system remains largely inactive. The unmyelinated free nerve endings are depolarized only by the application of mechanical forces sufficient to deform or damage the tissue that contains them or after exposure to sufficient concentrations of irritating chemical substances (lactic acid, serotonin, prostaglandins and histamine), released from local inflammatory cells and from the peripheral terminals of the primary afferent fibres themselves.8–10

Another important influence on nociceptor sensitivity is the pH of the tissue. High local concentrations of protons are known to occur in inflammation and the consequent reduction in pH contributes to the sensitization of nociceptors.11,12

Afferent nociceptive system

Nerve impulses generated at the nociceptive receptor system are delivered into the spinal cord by small myelinated and unmyelinated nerve fibres (5 µm or less in diameter), that mainly belong to the Ad and C groups of afferent nerve fibres (Fig. 1.1). Their cell bodies are located in the dorsal root ganglia of the spinal nerves. The very small diameter of the C nerves explains their slow conduction velocity (1 m/s), and their extreme sensitivity to blockade by local anaesthetic drugs. The myelinated Ad fibres are slightly larger and have a faster conduction velocity (10 m/s).13

The nociceptive afferents enter the spinal cord, where they divide into short ascending and descending branches, before they terminate at synapses on various groups of relay neurones in the dorsal horn of the spinal grey matter. Most of the connections are to the neurones in the basal spinal nucleus (at the base of the dorsal horn).14,15

The efferents of these cross the cord obliquely to turn upwards on the contralateral side and form the anterolateral spinal tract, which connects the basal spinal nucleus with the thalamic nuclei and has therefore traditionally been called the ‘spinothalamic tract’. Most of the fibres in this tract, however, do not directly ascend to the thalamus without interruption, but instead synapse with neurones in the brainstem reticular system, while others re-enter the spinal grey matter to synapse with internuncial neurones.16 However, the majority of the ascending nociceptive inputs terminate (sometimes after crossing several synapses) in the thalamic nuclear relay sites.17 It should be emphasized that not only do the neurones in the thalamic centres respond to peripheral noxious stimulation but they can also be activated by mechanoreceptor peripheral stimulation (see Pain modulation systems below).

The axons of the thalamic nuclei then ascend to the neurones of the cerebral cortex. Three thalamocortical projections can be defined: those responsible for perception; those related to the emotional experience; and those responsible for memory.18

The first project to the superior paracentral region of the cerebral cortex and seem to contribute to the so-called ‘perceptual component’ of pain – the patient's ability to perceive whereabouts (in which segment of his body) the pain is localized.19

The activation of the second thalamocortical projection system, projections that pass from the medial and anterior thalamic nuclei to the frontal lobes, evokes the emotional disturbances related with pain.20 Thus, a stimulus ‘hurts’ only when the nociceptive afferent projections arrive at the frontal cortex.

A third thalamocortical projection system links some of the medial thalamic nuclei to the cortex of the ipsilateral temporal lobe. Here the recent and long-term memory storage systems of the brain are located.21,22

A fourth projection system exists which relates some thalamic nuclei to subjacent hypothalamic nuclei in the ventral diencephalon. It is very probable that this thalamohypothalamic system provides the means whereby nociceptive afferent activity entering the brain evokes the complex of visceral reflex (cardiovascular and gastrointestinal) effects and hormonal changes that are so often associated with the experience of pain.23

In conclusion, activity of nociceptive receptors distributes pain into four different projecting systems in the brain, each contributing to a specific component of the global experience ‘pain’. However, the projection of pain from a peripheral...