Reward, motivation, and emotion of pain and its relief.

Although pain is familiar to almost everyone, its precise definition continues to be elusive. Pain is most often viewed in the realm of somatosensation. However, this conceptualization is problematic as unlikemost other sensations that are usually affectively neutral, pain has the additional quality of aversiveness. To focus only on aversive qualities is also problematic as there are many aversive conditions that are clearly recognized by humans as something other than pain. Fields has described the unique features of pain aversiveness as a quality of “algosity.” The qualities that make pain unique, and immediately recognizable to humans, have been discussed since antiquity. Aristotle proclaimed the doctrine of the 5 senses (sight, hearing, smell, taste, and touch) but did not include pain. For the ancient Greek philosophers, pain was included with pleasure as “passions of the soul.” Although not technical, this definition was nevertheless elegant and meaningful. The recognition of pain and pleasure as opposites on a hedonic spectrum revealed an understanding that these 2 emotions provide motivations that guide our decisions for action selection, shaping the lives of organisms. Pain is a call to action. Like hunger, thirst, and desire for sleep, pain is a part of the body’s survival systems that collectively are responsible for protecting the organism. These primordial emotions, including pain, are characterized by a specific sensation that signals deviation from homeostasis and an intention to satisfy the need for homeostatic balance. The sensation of pain generates an aversive state that demands a behavioral response (for pain, a motivation to seek relief). In contrast, relief of pain, and return to homeostatic balance is rewarding (see section 1.3). Because primordial emotions often signal that the very existence of the organism is threatened, they are ancient and encoded by phylogenetically conserved neural circuits consisting of afferent sensory pathways and areas of the brain including the thalamus, insula, and cingulate cortex. These cortical regions have connections with the valuation/decision mesolimbic circuit, which integrates the information from multiple competing emotions and selects the behavioral action that offers the greatest benefit to the organism. The mesolimbic system also serves in learning the situations that lead to deviation or restoration of homeostasis and thus helps the organism to avoid aversive situations and find rewards. Melzack and Casey first proposed the multidimensional model of pain in 1968. An important concept that emerged from this model was the partial separation of the affective and motivational features of pain from its sensory and discriminative qualities. Separation of these features also implied different anatomical substrates which were suggested to involve medial and lateral ascending pathways for affective/motivational and sensory/discriminative features, respectively. Viewing pain as a human experience that involved the synthesis of sensory, affective, and cognitive dimensions represented a momentous shift from unidimensional sensory models and underscored the distinction between pain and nociception and the lack of consistent relationship between pain and the state of the tissues. These concepts were based on clinical observation including, for example, the early studies byBeecher that soldiers in battle with serious wounds did not report feeling pain. Such findings were explained, in part, by the gate control theory of pain proposed by Melzack and Wall in 1965. Melzack wrote that neural signals never enter the nervous system as a blank canvass. Rather, nociceptive signals are always subject to interpretation of meaning based on the present context and of the past experience (ie, learning and memories). Fields has subsequently characterized descending bidirectional pain modulatory circuits that can enhance or diminish pain based on multiple factors including context, stress, expectation, and others (for review). The role of these descending circuits in circumstances of competing motivations such as reward and threat have led to the formulation of the motivation-decision model of pain (see below). Although the deconstruction of pain into multiple dimensions has been extraordinarily useful, the human experience of pain seems to require synthesis of all these components including affective, sensory, and cognitive dimensions. Ploner et al. reported a patient with a stroke-induced lesion in the somatosensory cortex who could not identify the source of a nociceptive stimulus on the contralateral side but found it unpleasant. However, the patient refused to identify the unpleasant nature of the stimulus as “pain,” supporting both the partial dissociation between sensory and affective qualities of pain and the need to integrate these qualities to form the human experience. Fields has elegantly noted that while the affective dimension of pain is partially separable from its “sensory” qualities, pain affect is nevertheless tightly related to the degree of nociceptive inputs and can therefore be appropriately termed “sensory” as well. Evidence of partial dissociation of affective and sensory features of pain also emerge from cingulotomy studies where “pain” continues to be perceived but is considered no longer bothersome, as well as from imaging studies where Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.