Pain, defined as ‘an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage’ by the International Association for the Study of Pain, is a multi-dimensional experience that is essential for the maintenance and survival of an individual. For the past 100 years, pain has been viewed by most investigators as a component of the classical somatosensory system, like the sense of touch. Pain as a sensory experience can clearly be regarded as a discriminative somatic sensation; the sensation can be localized, scaled, and timed, and different qualities of pain can be distinguished, for example, burning, stinging, or aching. However, pain is inherently and essentially an emotional/affective/ motivational feeling (unpleasantness), which can be differentiated from long-term suffering. Pain warns of abnormal conditions which threaten the integrity of the body, conditions that internal homeostatic mechanisms alone cannot rectify and that require motivation of contextually appropriate behaviour. From this perspective, pain is a feeling from the body, like temperature, itch, tickle, vasomotor flush, hunger and thirst, that signals one aspect of the physiological condition of the body itself.

Recognizing this, Sherrington (1905) considered pain, temperature and visceral sensations as components of interoception, or the sense of the body itself (or as he put it, the ‘material me’), which he differentiated from the exteroceptive sense of touch, the proprioceptive sense of limb position and movement, and the teloreceptive senses (hearing, vision). This view is intuitively parsimonious with the common knowledge that pain is an aspect of ‘how you feel’ that depends on many variables; in different words, pain is a specific somatic distress signal that is integrated within the contexts of current physiological and environmental conditions and past experience. This view was largely abandoned by investigators who sought to gate pain with the sense of touch, but it is strongly indicated by recent findings.

In this lecture, I will summarize functional and anatomical evidence supporting the concept that pain is an aspect of homeostasis, a term coined by Cannon (1932) that encompasses the ongoing systemic and neural processes by which the body maintains optimal conditions necessary for survival. The afferent neural input required for homeostatic integration provides the basis for the interoceptive sense of the body’s physiological condition. Under normal circumstances, small-diameter primary afferent fibres convey activity reporting the status of the tissues of the body to central pathways that engage protective and supportive mechanisms at several functional levels, i.e. autonomic, homeostatic, motoric, behavioural, and finally perceptual and mnemonic levels, and these responses must be integrated with ongoing homeostasis and behaviour. These fibres terminate in laminae I and II of the superficial dorsal horn of the spinal cord. The neurons in lamina I that provide the output from this region convey a modality-selective, ‘labelled line’ representation of the physiological condition of the body. These neurons receive descending controls from the pre-autonomic sites in the brainstem and the hypothalamus, and they project to the spinal sympathetic preganglionic cell column and to pre-autonomic, homeostatic integration sites in the brainstem, including the parabrachial nucleus, which integrates both spinal lamina I (i.e. sympathetic) and vagal (i.e. parasympathetic) afferent homeostatic inputs.

In addition, lamina I spinothalamic neurons project in primates by way of the classical lateral spinothalamic tract to a specific thalamo-cortical relay nucleus that conveys activity to an interoceptive representation in the insular (i.e. not parietal somatosensory) cortex. This cortical representation of the condition of the body incorporates both lamina I and parabrachial afferent activity, and it is well-developed only in humans; furthermore, this pathway provides a neural basis for subjective awareness of the state of the body, a sense which was predicted by Wm. James and which is the keystone for the ‘somatic marker’ hypothesis of consciousness proposed recently by A. Damasio. The concept that pain, temperature and itch sensations are interoceptive sensations that are affected by homeostatic integration incorporates all of these findings, and this concept provides a fundamental scientific basis for treating pain clincially with an integrative, wholistic approach.

This work was supported by the NIH and the Atkinson Pain Research Fund.