The Emotional Aspect of Pain
C. Richard Chapman Departments of Anesthesiology and Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington 98195 and Pain and Toxicity Research Program, Division of Clinical Research, Fred Hutchinson Cancer 6Research Center, Seattle, Washington 98104 Pain control merits high priority in the care of patients with cancer for several reasons, but chief among them is the prevention of needless suffering. Pain is more than a relentless sensory irritation signaling tissue trauma. Every clinician who has cared for cancer patients knows that pain causes anguish. In this respect, it is a powerful, compelling negative emotion that demands its own cessation.
Ancient Eastern philosophers such as Buddha emphasized the emotional nature of pain above the sensory, and the Greeks, although focused on sensations, nonetheless observed the emotional quality of pain (8). Aristotle described pain as a passion of the soul, and this concept survived for more than two millennia. Many ancient writers recognized the sensory features of pain, but they attributed its origin to the heart, a concept that apparently originated in Egypt, as it appears in the Ebers papyrus. Contemporary pain researchers still recognize the intrinsic affective character of pain, at least in formal definition. The International Association for the Study of Pain acknowledged the central role of affect in pain in its formal definitions: ``Pain [is] an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage'' (italics added) (50).
Sensory and affective aspects of pain appear to serve different, albeit complementary, purposes. The sensory component of pain detects, localizes, and characterizes injury signals. Sensory processes hold the key to understanding the origins of pain, its centripedal transmission, and its modulation, but the emotional processes interpret the biological threat of the noxious event to the individual, representing this subjectively in terms of negative feelings, physiologically as central nervous system and neuroendocrine arousal, and behaviorally as avoidance or escape activities. While the sensory aspect of pain informs, the emotional aspect interrupts ongoing goal-directed activities, disturbs normal biorhythms, particularly sleep, and compels expression through facial grimace, altered posture, diminished activity, guarding behaviors, and verbal complaint. This expression recruits support from the social environment. The emotional aspect, therefore, determines the suffering that accompanies pain.
The purposes of this chapter are to explore the concept of the affective dimension of pain, to review briefly current knowledge and research issues in relevant fields of emotion research, to propose a model for the mechanisms of affect during pain, and to explore implications of this model for patient care.
We all know emotions as sensation-like feeling states that compel us to act in certain ways. Nonetheless, the literature yields poor consensus on a definition for emotion; multiple theorists create a plethora of meanings for the term, perhaps because the concept of emotion encompasses a wide range of animal and human phenomena. For example, Rolls (65) stated ``Emotions can be usefully defined as states elicited by reinforcing stimuli.'' Fonberg (23) contended that ``[e]motion is the nervous process that determines what kind of stimuli coming from the inner and outer environments are desirable for the organism and what are not.'' In contrast, Averill (6) stated that ``[a]n emotion is a transitory social role (a socially constituted syndrome) that includes an individual's appraisal of a situation and that is interpreted as a passion rather than as an action.'' Such seemingly unrelated definitions of the term reflect the divergent theoretical frameworks within which emotion researchers work, and they often account for different subjective, behavioral, or social phenomena.
In keeping with ancient traditions, some contemporary theorists argue for a set of fundamental emotions, from which all others derive. Plutchik (60) listed eight basic emotions. The subjective feelings, associated behaviors, and sociobiological functions associated with these emotions are as follows:
In contrast, MacLean (47) postulated three classes of affects: basic, general, and specific. Basic affects derive from basic needs such as hunger, the urge to urinate, or sexual expression. General affects are complex feelings aroused by situations, other people, or things. Specific affects correspond to specific sensory experiences such as smells or sounds. Pain falls into this class of experience, since we experience it as a bodily sensation. Ictal aura phenomena often provide striking examples of emotions in this class, and MacLean has noted many instances of ictal emotions involving bizarre pain states.
These differences typify the lack of consensus in the field about basic emotions. One could draw many other lists of basic emotions from the literature. While some writers argue for a set of fundamental emotions, those who do so cannot agree on what these are. Other theorists contest the assumption that basic emotions exist (53).
Despite many bones of contention concerning basic concepts, sufficient consensus exists among theorists that mainstream emotion researchers largely agree on the following points:
These points of agreement help to clarify what science currently means by emotion, but a conclusive definition for emotion still eludes us. This is unfortunate, for without this our definition of pain remains incomplete.
In approaching the emotional dimension of pain, I favor a sociobiological (evolutionary) framework that interprets feeling states, related physiology, and behavior in terms of adaptation and survival. Nature has equipped us with the capability for negative emotion for a purpose; bad feelings are not simply accidents of human consciousness. By understanding the emotional dimension of pain from this perspective, we may gain some insight about how to prevent or control emotions that foster suffering.
Emotions and the emotional dimension of pain characterize mammals in general. MacLean (47) contended that emotions ``impart subjective information that is instrumental in guiding behavior required for self-preservation and preservation of the species. The subjective awareness of affects is characterized by a sense of bodily pervasiveness or by feelings localized to certain parts of the body.'' Emotion evolved to facilitate adaptation and survival, and negative emotion is particularly important. The ability to impute threat to certain types of events protects against lifethreatening injury.
Viewed from the perspective of subjective experience, the brain's representation of threat is a feeling state. The emotional intensity of an experience marks the adaptive significance of the event that produced the experience. The emotional magnitude of a pain, therefore, is the internal representation of the threat associated with the event that produced the pain.
Emotions require expression through vocalization, posture, variations in facial muscular patterns, and alterations of activity. This enhances communication and social support, thus contributing to survival. Darwin (17) recognized early on that emotions enable communication through vocalization, startle, posture, facial expression, and other behaviors. Contemporary investigators who study emotions and human or animal social behavior emphasize that communication is a fundamental adaptive function of emotion (59). Social mammals, including humans, use one another or their social group as resources for adaptation and survival. The emotional expression of pain in the presence of supporting persons is socially powerful; it draws on a fundamental sociobiological imperative, communicating threat and summoning assistance.
In brief, negative emotions interpret and scale the negative importance of an event, communicate this interpretation to others, and guide behavior appropriately. Loss of a loved one produces grief (awareness of loss), the expression of grief affects others, and the emotion produces grieving behaviors. In a similar way, fear and pain lead to expression that tends to elicit social support and appropriate behaviors.
The part of the brain that Broca called the ``great limbic lobe'' appears as a common denominator across mammalian species (47). Early investigators focused on the role of olfaction in limbic function. Papez (57) linked the limbic brain to emotion, stating ``It is proposed that the hypothalamus, the anterior thalamic nuclei, the gyrus cinguli, the hippocampus and their interconnections constitute a harmonious mechanism which may elaborate the functions of central emotion, as well as participate in emotional expression.''
MacLean (46) introduced the term limbic system four decades ago and characterized its functions. Currently, he identifies three main subdivisions of the limbic brain: amygdala, septum, and thalamocingulate (47). Figure 1 illustrates three main subdivisions of the limbic brain. These represent sources of afferents to parts of limbic cortex (47). He also postulated that the limbic brain responds to two basic types of input: interoceptive and exteroceptive. In the tradition of Sherrington these refer to sensory information from internal and external environments, respectively.
Traditionally, neurological research has not linked pain to limbic processing. However, anecdotal evidence implicates limbic structures in the distress of pain. Now outdated radical frontal lobotomies performed on patients for psychosurgical purposes typically interrupted pathways projecting from hypothalamus to cingulate cortex and often relieved the suffering of intractable pain without destroying sensory awareness (27). Such neurosurgical records help clarify recent positron emission tomographic and magnetic resonance imaging observations of human subjects undergoing painful cutaneous heat stimulation: noxious stimulation activates contralateral anterior cingulate as well as primary and secondary somatosensory cortex (75).
The affective component of pain fosters adaptation through instrumental (operant) learning as well as classical conditioning (learning by association). Operant learning requires reinforcers, and reinforcers are events accompanied by emotions. Classical conditioning represents the formation of an association between a normally neutral event and the negative emotion associated with the onset of pain. Both of these mechanisms contribute to emotional differences in cancer patients encountering painful procedures or undergoing pathological pain. Memory of past events, like learning, depends heavily on emotion, and memories of past experience tend to shape expectations for the present and future.
Operant learning can occur in any setting where patients are active and reinforcing events take place. A reinforcer is an event that alters the future likelihood of a behavior occurring when it follows an instance of that behavior (26). Positive reinforcing events creating pleasure are rewards; negative ones producing pain are punishments (i.e., they suppress behaviors). The positive or negative nature of reinforcers and their personal significance occur in conscious awareness as feelings (65). Put another way, reinforcing events are those that are emotionally salient. Emotion-free events have no reinforcing properties and therefore cannot contribute to adaptive learning.
Fear accompanying pain can be classically conditioned to nonnoxious stimuli. In fear conditioning, the repeated pairing of a neutral stimulus with a noxious one can condition the perceiver so that the neutral stimulus, occurring alone, acts as a trigger to elicit fear. Biologically, fear conditioning supports survival by ensuring avoidance of potentially dangerous situations. Through conditioning ordinarily neutral stimuli becoming warning cues for danger (71). It also helps the individual marshal a flight-or-fight response to a challenge after preexposure to it. Osborne et al. (54) found that MHPG (3-methoxy-4-hydroxyphenylglycol), an indicator of norepinephrine turnover in the brain, provided a marker of fear conditioning; exposure to a painful event increased MHPG in a manner that tracked the conditioning process.
Conditioned emotional responses are essentially sensory-affective associations. The amygdala appears to be the key structure in the linking of sensory experience to emotional arousal and in the conditioning of negative emotional associations (23,30,42). It probably contributes to the emotional evaluation of cognitive events (via corticofugal pathways) as well as sensory events that reach it via the DNB or sensory thalamus. Aggleton and Mishkin (2) described the amygdala as a gateway to the emotions for stimuli (simple or complex) in all sensory modalities, both conditioned and unconditioned.
LeDoux and colleagues (42,43), working with auditory stimuli, determined that projections from acoustic thalamus to the amygdala allow the classical conditioning of emotional responses to normally neutral auditory stimuli in experimental animals. To condition subjects, they paired tones with footshock, evaluating autonomic responses and emotional behaviors. Lesion work implicated separate efferent projections from the amygdala in conditioning of autonomic and behavioral responses. These and other observations suggest that emotion is a complex process sustained by several mechanisms; under controlled circumstances individual mechanisms can be independently conditioned.
Fear conditioning almost certainly occurs in cancer patients who undergo repeated painful procedures. Fear conditioning can exacerbate the affective dimension of pain in cases where minor pain and intense affective arousal have been paired. Moreover, it can form associations between the environment surrounding a painful event and affective processing of that event so that the environment alone could elicit elements of the affective dimension of pain. Fear conditioning may contribute to phobic behavior patterns in pediatric patients.
Emotion associated with pain also influences memory. Memory researchers surmise that both limbic and nonlimbic mechanisms contribute to memory processes (28). Emotional significance controls at least some and perhaps much memory formation: evidence exists that the brain preferentially stores information that has strong emotional loadings (9,76). Heath (31) proposed that learning and memory are ``rooted in feeling and emotion'' and identified hippocampus, cortical medial amygdala, and cingulate gyrus as key areas involved in negative emotions. Thus, the emotional component of pain seems to support adaptation and survival by facilitating learning, memory, and related cognitive processes.
Negative emotions appear to be much more than reactions to undesirable events; they equip an individual with a capability to determine which things benefit and which things threaten survival, and they compel behavior consistent with such evaluations. Moreover, they communicate this judgment to others and set up group approach or avoidance behaviors. As noted above, MacLean (47) described emotion as a process that imparts subjective information. In these respects, emotion approximates a crude intelligence. If emotion is a proto-intelligence, then evolutionarily newer structures, namely the later stages of cortical development, should have demonstrable links with limbic structures and functions.
Such interconnections exist. Parts of the frontal lobe (the dorsal trend) appear to have developed from rudimentary hippocampal formation, whereas other parts (the paleocortical trend) originated in olfactory cortex. Although these two areas are anatomically interconnected, the former analyzes sensory information and the latter contributes emotional tone to that sensory information (55). Pribram (61), noting that limbic function involves frontal and temporal cortex, offered a bottom-up concept for how cognition relates to feelings; that is, emotion determines cognition. However, the multimodal neocortical association areas project corticofugally to limbic structures (77) and this suggests that cognitions may drive emotions. Plutchik (60) argued that cognitions (evaluations) always precede emotions and may be based upon information provided by internal or external stimuli. These points of view may not be as diametrically opposed as they appear. Plutchik has postulated that emotions precede cognitions in evolution and that cognitions evolved in the service of emotions. The sociobiological purpose of cognition, for Plutchik, is to predict the future. Good agreement exists among theorists that human thinking involves intimate interplay with emotions.
Negative emotion is not only a part of pain; in many instances it surrounds pain. Patients who undergo painful procedures repeatedly develop conditioned fear and enter the painful situation in a state of emotional distress. Others entering a potentially painful situation for the first time generate cognitively mediated fear. The physiology of such emotional states may interact with the painful event itself. In addition, because pain possesses inherent negative emotional qualities, emotion occurs during a painful experience. When the pain has been severe, prolonged, or both, the negative emotion endures well beyond the sensory awareness of pain so that the patient feels aroused and distressed for a long while.
These considerations suggest that, in contrast to the sensory aspect of pain, the emotional aspect precedes, coexists with, and follows the noxious event.
Central sensory and affective central pain processes share common sensory mechanisms in the periphery: A-delta and C fibers serve as tissue injury transducers (nociceptors) for both, the chemical products of inflammation sensitize these nociceptors, and peripheral neuropathic mechanisms such as ectopic firing excite both processes. Differentiation of sensory and affective processing begins at the dorsal horn of the spinal cord with sensory transmission following spinothalamic pathways and affective transmission taking place in spinoreticular pathways. As others have described sensory processing of nociception well (8,21,58,81), it need not be reviewed here.
Nociceptive centripetal transmission engages spinoreticular as well as spinothalamic pathways (78). The spinoreticular tract contains somatosensory and viscerosensory afferent pathways that arrive at different levels of the brain stem. Spinoreticular axons possess receptive fields that resemble those of spinothalamic tract neurons projecting to medial thalamus and, like their spinothalamic counterparts, they transmit tissue injury information (8,21,79). Most spinoreticular neurons carry nociceptive signals and many of them respond preferentially to noxious input (1,7,10,81).
Processing of nociceptive signals to produce affect commences in reticulocortical pathways. Four extrathalamic afferent pathways project to neocortex: the dorsal noradrenergic bundle (DNB) originating in the locus coeruleus (LC); the serotonergic fibers that arise in the dorsal and median raphe nuclei; the dopaminergic pathways of the ventral tegmental tract that arise from substantia nigra; and the acetylcholinergic neurons that arise principally from the nucleus basalis of the substantia innominata (24). Of these, the noradrenergic pathway links most closely to negative emotional states (29,30). The set of structures receiving projections from this complex and extensive network corresponds to the classic definition of the limbic brain (29,34,46,57).
Although other processes governed predominantly by other neurotransmitters very likely play important roles in the complex experience of emotion during pain, I focus on the role of central noradrenergic processing here. This processing can be described in terms of two central noradrenergic pathways: the dorsal and ventral noradrenergic bundles.
The pontine nucleus, LC, is positioned bilaterally near the wall of the fourth ventricle. It has three major projections: ascending, descending, and cerebellar; the ascending projection, known as the DNB, is the most extensive and important (22). Figure 2 illustrates these structures. The DNB projects from the LC throughout limbic brain to all of neocortex, accounting for approximately 70% of all brain norepinephrine (74,80). The LC gives rise to the majority of central noradrenergic fibers in spinal cord, hypothalamus, thalamus, and hippocampus (5,44) in addition to the projections to limbic cortex and neocortex.
The LC reacts to sensory stimuli that potentially threaten the biological integrity of the individual or signal damage to that integrity. Nociception inevitably and reliably increases activity in neurons of the LC, and LC excitation appears to be an inevitable response to nociception (39,51,72,74). Notably, this does not require cognitively mediated attentional control since it occurs in anesthetized animals. Foote et al. (25) reported that slow, tonic spontaneous activity at LC in rats changed under anesthesia in response to noxious stimulation. Experimentally induced phasic LC activation produces alarm and apparent fear in primates (15,64), and lesions of the LC eliminate normal heart rate increases to threatening stimuli (63).
The LC responds consistently, although not exclusively, to nociceptive sensory input. Increased LC activity ensues following nonpainful threatening occurrences such as strong cardiovascular stimulation (20,51) and certain visceral events such as distention of the bladder, stomach, colon, or rectum (19,74). Thus, while it reacts to nociception, the LC is not a nociceptive-specific nucleus. The LC may be a central analog of the sympathetic ganglia (3). It responds to biologically threatening events, of which tissue injury is a significant subset.
Studies of negative affect and vigilance behavior implicate the DNB as the largest and the most important LC projection for emotional processing of nociception. Vigilance and orientation to affectively relevant and novel stimuli can occur because of the DNB; it also regulates attentional processes and facilitates motor responses (13,18,24,29,74). Direct activation of the DNB and associated limbic structures produces sympathetic nervous system response and elicits in animals such emotional behaviors as defensive threat, fright, enhanced startle, freezing, and vocalization (49). In normal circumstances, activity in this pathway increases alertness; tonically enhanced LC and DNB discharge corresponds to hypervigilance and emotionality (12,25).
Biologically, the LC and DNB foster survival by allowing the individual to exercise global vigilance for threatening and harmful stimuli. Siegel and Rogawski (70) hypothesized a link between the LC noradrenergic system and vigilance through rapid eye movement (REM) sleep. They noted that LC noradrenergic neurons maintain continuous activity in the normal waking state and non-REM sleep but during REM sleep these neurons all but cease discharge activity. An increase in REM sleep ensues after either lesions of the DNB or administration of clonidine, an alpha-2 adrenoceptor agonist. LC inactivation during REM sleep (and rebuilding of noradrenergic stores) may permit sustained periods of high alertness during subsequent waking. Siegel and Rogawski (70) contended that ``a principal function of NE in the CNS is to facilitate the excitability of target neurons to specific high priority signals.'' Conversely, reduced LC activity periods (REM sleep) allow time for a suppression of sympathetic tone.
Collectively, these findings suggest that the affective dimension of pain shares central mechanisms with vigilance, a biologically important process. Vigilance, intensified by injury signals from within the organism, distressing environmental events from without the organism, or a combination of these, can progress to hypervigilance and panic. As a subjective experience, the emotional quality of pain seems, therefore, most accurately described as awareness of threat.
The ventral noradrenergic bundle (VNB), like the DNB, is an ascending noradrenergic system; it enters the medial forebrain bundle (see Fig. 2 ). Neurons in the medullary reticular formation project to hypothalamus via the VNB (8,73). Sawchenko and Swanson (67) identified two VNB-linked noradrenergic and adrenergic pathways to paraventricular hypothalamus in the rat and described them using the Dahlstr;auom and Fuxe (16) designations: the A1 region of the ventral medulla (lateral reticular nucleus [LRN]) and the A2 region of the dorsal vagal complex (the nucleus tractus solitarius [NTS]), which receives visceral afferents. These medullary neuronal complexes supply 90% of catecholaminergic innervation to the paraventricular hypothalamus via the VNB (4). Regions A5 and A7 make comparatively minor contributions to the VNB.
The VNB is important for emotion research because it innervates the hypothalamus. The noradrenergic axons in the VNB respond to noxious stimulation (74) as does the hypothalamus (38). Moreover, nociception-transmitting neurons at all segmental levels of the spinal cord project to medial and lateral hypothalamus and several telencephalic regions (11). These considerations suggest that threatening events, and particularly nociception, excite the hypothalamic-pituitary-adrenocortical (HPA) axis via several routes.
The coordinating center for the HPA axis is the hypothalamic paraventricular nucleus (PVN). Neurons of the PVN receive afferent information from several reticular areas including ventrolateral medulla, dorsal raphe nucleus, nucleus raphe magnus, LC, dorsomedial nucleus, and the nucleus tractus solitarius (45,58,67). Still other afferents project to the PVN from the hippocampus and amygdala. Nearly all hypothalamic and preoptic nuclei send projections to PVN.
The PVN responds to potentially or frankly injurious stimuli by initiating a complex series of events regulated by feedback mechanisms (see Fig. 3 ). These processes ready the organism for extraordinary behaviors that will maximize its chances to cope with the threat at hand (69). Cannon (14) described this ``flight or fight'' capability as an emergency reaction. Contemporary writers such as Henry (32) and LeDoux (43) have pointed out that neuroendocrine arousal mechanisms are not limited to emergency situations, even though most research emphasizes that such situations elicit them. In complex social contexts, submission, dominance, and other transactions can elicit neuroendocrine and autonomic responses, modified perhaps by learning and memory. This suggests that neuroendocrine processes accompany all sorts of emotion-eliciting situations.
Links between hypothalamus and autonomic nervous system reactivity have been recognized for decades (56). Psychophysiologists have long considered diffuse sympathetic arousal to reflect, albeit imperfectly, negative emotional arousal (41). The PVN invokes autonomic arousal through neural as well as hormonal pathways. It sends direct projections to the sympathetic intermediolateral cell column in the thoracolumbar spinal cord and the parasympathetic vagal complex, sources of preganglionic autonomic outflow (40). In addition, it signals release of epinephrine and norepinephrine from the adrenal medulla. These considerations implicate the HPA axis in the neuroendocrinologic and autonomic manifestations of affective changes during pain.
In addition to controlling neuroendocrine and autonomic nervous system reactivity, the HPA axis coordinates emotional arousal with behavior (56). Direct stimulation of hypothalamus can elicit well-organized patterns of behavior, including defensive threat behaviors, accompanied by autonomic manifestations (33,35,36,48). The existence of demonstrable behavioral subroutines in animals suggests that the hypothalamus plays a key role in matching behavioral reactions and bodily adjustments to challenging circumstances or biologically relevant stimuli. Moreover, stress hormones may affect central emotional arousal at high levels. Saphier (66) observed that cortisol altered the firing rate of neurons in limbic forebrain. The coordination of behavioral readiness with physiological capability, awareness, and cognitive function appears to be an executive responsibility of the HPA axis.
The model postulates a physiological basis for the affective dimension of pain and suggests that cancer patients contend with the negative emotion associated not only with pain's presence but also with its anticipation and its aftermath. It further suggests that the suffering of a patient is less a direct consequence of the sensory intensity of a patient's pain than of the distress that the pain causes. Often the emotional component of pain depends heavily on the duration of the pain and the ways in which pain disturbs normal circadian rhythms, general functional ability, and the presentation of the self in everyday life.
If emotional processes are a part of pain and the suffering that it entails, then the general affective status of the patient may prove valuable for predicting his or her ability to cope with painful procedures or the pain of disease. Given the common mechanisms of pain and anxiety/fear, it may prove beneficial to record at least a rough assessment of the anxiousness of the patient as well as any documented or apparent mood disturbance.
Pain measurement, from the sensory perspective, requires eliciting information from patients about pain intensity via self-report and recording that information. The model, however, recognizes that the expression of pain is a socially meaningful communication, and it may involve facial expression, postural change, altered voice, and behavioral components as well as the report of a subjective judgment. Ideally, the patient's report should match the nonverbal communication, but experienced clinicians know that this is not always the case. Many cancer patients, perhaps because they are aware of the emotional impact of communicating pain, tend to conceal or understate pain during transactions with physicians. Some patients deal with the threat that pain represents (e.g., a signal of disease progression) by denial and inaccurate attribution. In such cases physicians need to recognize other signs of pain and distress and to address them directly with patients and family so that patients can receive appropriate analgesic support.
The goals of pain control include preventing distress and suffering, not simply eliminating a sensation. The model suggests that the affective component of pain offers a pharmacological target. One can intervene pharmacologically in the affective dimension of pain by using beta-blocking drugs. Such drugs can attenuate central noradrenergic activity, thus minimizing hypervigilance and anxiety. However, this approach may be counterproductive. Noradrenergic mechanisms contribute to the modulation of nociception at spinal levels and descending noradrenergic neurons originating in the locus coeruleus contribute to endogenous analgesic activity (37,62,68). Beta-blocking drugs could prevent or compromise such modulation, thus accentuating nociception at the same time that they decrease central emotional arousal. This issue requires research to determine whether the anxiolytic gains exceed the costs in compromised endogenous modulation of nociception.
The long-recognized anxiolytic benefits of morphine have received little or no attention in studies of affect during pain. Morphine, and presumably other commonly prescribed opioid analgesics, can reduce fear by binding at receptors in cingulate cortex, at least in primates, as judged from isolation cry studies (82). Separation of a mammalian mother and her offspring results in a vocal expression of distress from the offspring: the separation or isolation cry (47). Noradrenergic circuits presumably mediate this vocalization. In squirrel monkeys morphine suppresses the separation cry and naloxone restores it (52). This phenomenon suggests that morphine exercises a sedative effect by inhibiting central noradrenergic circuits associated with negative emotional arousal.
Psychological approaches to pain control largely address the affective rather than the sensory component of pain. They allow caregivers to intervene in several ways, through cognitive mediation of emotional states (symptom relabeling, positive thinking, meditation), control of attention to somatic symptoms (e.g., hypnosis, escape into mental imagery), substitution of emotional states mutually exclusive to panic and hypervigilance (specifically deep relaxation, tranquillity), and maximizing exercise of personal control. These approaches offer great advantage on several counts: they require no prescription substances or devices, they incur no side effects, they can involve family and friends who want to help the patient, and they increase the patient's sense of personal control. However, psychological methods require time-consuming training, guidance, and follow-up from a psychotherapist, sustained practice on the part of the patient, and sufficient energy and functional capability for the patient to attain mastery of key skills. Mastery of psychological self-help skills relatively early in the course of disease can help assuage fears that the pain will eventually become unbearable.
Pain involves affective as well as sensory processing. It causes suffering by initiating complex emotional processes. Central noradrenergic pathways associated with hypervigilance and fear appear to respond to noxious events, producing a central negative emotional state during pain. The HPA axis further contributes to arousal by exciting neuroendocrine and autonomic mechanisms concomitantly. These mechanisms, rather than the sensory intensity of a pain, determine the distress that the patient feels, manifests, and communicates. Affective mechanisms of pain suggest hitherto overlooked therapeutic targets. Control of noradrenergically mediated negative emotional arousal may help alleviate the distress of cancer patients in pain.