Neurons involved in the exteroceptive function of pain

According to the schema introduced by Sherrington (1906), receptor systems belonging to the cutaneous senses may be included in the class of exteroceptors that are activated by objects in the external environment. In contrast, interoceptors are stimulated by bodily changes in the internal environment, most notably visceral structures such as the gastrointestinal tract. Geldard (1972) described interoceptors as the mediators of ‘organic sensations’, closely allied with information concerning the state of the body and hence homeostasis. More recently, Craig (2003a,b) has expanded this concept to view pain as a basic feeling or emotion that drives homeostatic behavior. In his view, pain serves exclusively an interoceptive function to provide a brain image of the ‘afferent representation of the physiological condition of the body’ (Craig, 2003b). In this review, evidence is presented to support the notion that pain has an exteroceptive function, extracting information about events in the environment in order to execute behaviors that protect the organism from external threats. When the skin of mammals comes into contact with external objects that can cause tissue damage, specialized nociceptors are activated, ultimately leading to the initiation of escape and avoidance behaviors providing for self-protection. This is analogous to visual or auditory receptors which signal events in the external environment (hence distant exteroceptors as defined by Sherrington) that can lead to protective behaviors such as escape and avoidance. In contrast, interoceptors are activated when deep tissues are injured or there is a state of dysfunction or disease within them. Unlike exteroceptor-initiated pain, interoceptive functions of pain are accompanied by homeostatic behaviors such as quiescence and guarding of injured body regions, and autonomic responses that promote recuperation and healing (Wall, 1979). Thus, one can envision two biological functions of pain: escape/avoidance of external threats, and protection of injured or dysfunctional tissues that disrupt homeostasis. Both functions protect the integrity of the body and pain is associated with both functions. Given these radically different functions of pain, the question arises as to the differential neural representations and mechanisms that serve them. The hypothesis and supporting evidence put forth here is that specialized nociceptive neurons in the central nervous system serve both exteroceptorand interoceptor-initiated pain and that they function in concert to do so.