An Introduction to Pain and its Relation to Nervous System Disorders

Abstract

Basic organisation of spinal pain pathways Primary afferent axons belonging to the somatosensory system can respond to a range of mechanical, thermal and chemical stimuli. Many of these afferents are activated by stimuli that damage (or threaten to damage) tissues, and these are known as nociceptors. Primary afferents that innervate the limbs and the trunk enter the spinal cord through the dorsal roots and form excitatory (glutamatergic) synapses with neurons in the dorsal horn. The dorsal horn contains a large number of neurons, the great majority of which have axons that arborise locally and remain in the spinal cord; these are known as interneurons and are involved in the local processing of sensory information. In addition, the dorsal horn contains projection cells-that is, neurons with axons that enter the white matter and travel rostrally to the brain. The axons of these cells are grouped into a number of different ascending tracts. The final neuronal component consists of descending axons, which originate from cells in the brain (particularly the brainstem) and terminate diffusely within the dorsal horn. Rexed (1952) divided the grey matter of the dorsal horn into six parallel laminae (numbered from dorsal to ventral), and this scheme is widely used, for example to describe the arborisation of primary afferents and the distribution of different populations of spinal neurons (Figure 1.1). The dorsal horn is somatotopically organised, the body being mapped in a bidimensional pattern onto the rostrocaudal and mediolateral axes. The other, dorsoventral dimension is arranged in a modality-specific pattern, as will be described later. Fifty years ago, Melzack and Wall (1965) proposed that neurons within the superficial dorsal horn could 'gate' the inputs from nociceptors and thus modify the perception of pain. This theory attracted a great deal of interest, and there have been numerous attempts to unravel the neuronal circuitry that underlies pain processing in the spinal cord. It turns out that this circuitry is highly complex, and we still have only a limited understanding of it. Nonetheless, it is clear that this region is very important for modulating pain in both normal and pathological states. The superficial dorsal horn is also likely to provide important targets