Indian J Physiol Pharmacol 2002;46 (4);

Pain measurement: a formidable  task
SANHAY KUMAR *, O .P. TANDON ** AND R.  MATHUR***
Departments of physiology,
*B.P.K.I.H.S., Dharan, Nepal,
**University College of Medical Science,
Shahdara, Delhi – 110 095
and
***All India Institute of Medical Sciences,
New Delhi – 110 029
(Received on July 26, 2001)

 

           Abstract: Pain is defined as unpleasant sensory and emotional experience, associated with actual or impending tissue damage. It consists of multi-dimensional phenomenon having sensory discriminative, cognitive-evaluative and effective motivational components. Though the technology has advanced, still it is very difficult to objectively assess all the attributes of pain, including alteration in cognitive behaviour. However, subjective methods like Visual Analog Scale rating (VAS) and preliminary objective methods like pain evoked responses, behavioural monitoring and event related evoked potentials for cognition are currently in vogue. It will take some more time and effort to evolve yet other newer and sophisticated techniques to measure all aspects of pain in human beings.

 

Key  words :    Pain,event related evoked potentials,Cognition,VAS,pain evoked potentials

 

Introduction
Pain measurement in humans
Subjective pain assessments
Behavioural and physiological measures
Electroencephalography
Pain evoked potentials
Event related potentials (ERP)
References



INTRODUCTION

A committee of The international Association for the study of pain has defined pain in humans as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage (1). Thus pain is more than just a physiological transmission of nociceptive impulses. Therefore, an ideal assessment should include measurement of the interplay of different factors on the total experience of pain. Throughout most of recorded history, pain was characterized as an effective feeling state rather than a sensation (2). Emotions play key role in painful experience. Aristotle described pain as a “passion of soul”, distinct from the classic five senses (3). Melzack and Wall (4) and Melzack and Casey (5) developed a model of pain in which tissue damage concurrently activates sensory-discriminative, cognitive-evaluative and affective-motivational components of pain. The nature and severity of pain then become consequences of affective and cognitive mechanisms as well as sensory events deriving from tissue damage. Thus, pain is a complex physiological-behavioral puzzle that requires assessment on different levels. At the same time the measures of pain should be reliable and valid, otherwise they will be little use to clinicians or researchers.

An ideal pain measure should (6): Provide sensitive measurement free of biases, provide immediate information about accuracy and reliability, separate the sensory-discriminative aspects of pain from its hedonic qualities, assess experimental and clinical pain with the same scale and provide absolute scales that allow assessment of pain between groups and within groups over time. A valid, reliable and flexible measurement technology becomes a prerequisite for evaluation of this. Progress in this domain has been extremely slow but steady, because pain, as pointed out earlier, is a subjective experience (7). However, in the recent past, technologies for the non-invasive assessment of brain function have advanced at a rapid pace. Amongst the techniques for measurement of brain electrical activities and topographic mapping are quantitative analysis of cortical power spectrum (CPS), as well as the computerised averaging of Brain Evoked Potentials (EPs). The availability of modern technology for imaging of brain and measurement of certain processes in brain is a significant progress in science and also for pain studies (8). These parameters can now be recorded non-invasively from awake humans for correlating with conscious reporting of pain and other subjective experiences. This includes Evoked potentials (EP), Nuclear Magnetic Resonance (NMR), Position Emission Tomography (PET) etc.
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Pain measurement in humans

Pain is both a somatic sensation and a powerful feeling state, which evokes behaviours that minimize harm and promote healing (9). Melzack and Dennis (10) considering the vague and diffuse feelings associated with pain observed that “The effective dimension is difficult to express in words such as exhausting, sickening, terrifying, cruel, vicious and killing”. Individual differences in the experience of pain (11) and variability among painful conditions (12) complicate the task. Patients may not only have difficulty describing painful experiences, but they may also be unwilling or reluctant to confide these feelings of distress. Moreover, voluntary control can be used to suppress or exaggerate the expression of pain (13).

Pain measurement studies during past century are focused on the psychophysical relationship between the extent of injury and perceived pain. Excellent psychophysical power functions were generated. All studies of pain measurement up to the time of publication of the gate control theory of pain (4) concentrated exclusively on the measurement of pain intensity. The gate control theory, together with the increasing emphasis on pain as a major clinical problem (14, 15, 16), led to the recognition that pain rarely has a one-to-one relationship to a stimulus. Acute pain is sometimes proportional to the extent of injury, but the contribution of psychological factors reveals complex relationship that are profoundly influenced by fear, anxiety, cultural background and the meaning of the situation to the person (17). Chronic pain presents an even greater problem for the psychophysical concepts: backaches often occur without any discernible organic cause; post herpetic neuralgia persists long after peripheral nerve regeneration and healing of all tissues. The measurement of pain intensity is essential to determine the initial intensities, perceptual qualities and time-course of the pain so that the differences among different pain syndromes can be ascertained and investigated. Measurement of these variables provides valuable clues that help in the differential diagnosis of the underlying causes of the pain. They also help determine the most effective treatment necessary to control pain and essential to evaluate the relative effectiveness of different therapies.

The pain threshold can be determined by the classical (18) methods of limits (ascending and descending trials). Simple category scales such as the four-point ‘none, mild, moderate and severe’ (Verbal categorical scale) or 1-10 numerical scale can be scored in several ways. The simplest, the method of equal appearing intervals, assigns successive integers to verbal categories or uses numerical categories directly (19). The three most frequently considered aspects of pain are the subjective (measured by self-report), the behavioural (measured by sampling of physiological or electric potentials and assaying body fluids or other biological responses). Self-report measures, when they can be obtained should be regarded as the ‘Gold standard Indeed, the International Association for the study of pain emphasizes that pain is always subjective.

Fortunately, techniques for the psychological assessment of the pain patients have improved to the extent that emotional states such as anxiety, depression and defensive personality styles can now be identified. People experiencing pain are able to report separately on the sensory and affective dimensions and emotional qualities differ dramatically across different forms of clinical pain and within individuals over time (20). Currently evidence indicates that pharmaceutical and psychological interventions have different effects on either sensory, affective or both qualities of the experience. The narcotic Fentanyl reduces the sensory intensity but not the unpleasantness of painful tooth pulp sensations (21). In contrast, anxiolytics such as Diazepam reduces affective discomfort rather than sensory-intensity qualities of the experience (22). Similarly, placebo medication has an impact on unpleasantness rather than on sensory qualities of painful events. The new emphasis on the varieties of clinical pain and their variability have led to new concepts of pain measurement.
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Subjective pain assessment

A Visual analogue scale (VAS) is a simple measure of subjective pain. It consists of 10 cm horizontal (23) or vertical (24) line with the two endpoints labeled ‘no pain’ and “worst pain ever’. The subject is required to place a mark on the 10 cm line at a point, which corresponds to the level of pain intensity he or she presently feels. The distance in centimeters from the lower end of the VAS to the patient’s mark is used as a numerical index of the severity of pain. The VAS is sensitive to pharmacological and non-pharmacological procedures that alter the experience of pain (25, 26) and correlates highly with pain measured on verbal and numerical rating scales (27, 28). The ease of administration and scoring has contributed to the popularity of this method. A major advantage of the VAS as a measure of sensory pain intensity is its ratio scale properties (29). Other advantages include minimal intrusiveness and conceptual simplicity (23, 30). The major disadvantage of the VA is its assumption that pain is a one-dimensional experience (30).

Melzack and Togerson (31) developed a questionnaire to specify the qualities of pain. The three major classes were words that describe sensory qualities (temporal, spatial, pressure, thermal and other properties), affective qualities (tension, fear and autonomic properties) and evaluative qualities. The questionnaire, which is known as the ‘McGill Pain Questionnaire (MPQ)’ (30), has become a widely used clinical and research tool (8, 32, 33). MPQ has been translated into several languages. The most important requirement of a measure is that it should be valid, reliable, consistent and, above all, useful. The MPQ appears to meet all of these requirements (7, 31, 32, 33) and provides a relatively rapid way of measuring subjective pain experience (30).

Turk et al (34) and Holroyd et al (35) evaluated the theoretical structure of the MPQ. Turk et al (34) concluded that the three-factor structure of the MPQ (sensory, affective and evaluate) is strongly supported by the analysis. However, these authors argue that the factors measured by the MPQ are highly intercorrelated, they are therefore not distinct. It is evident, however, that the discriminative capacity of the MPQ has limits. High level of anxiety and other psychological disturbances, which may produce high affective score, may obscure the discriminative capacity. Moreover, certain key words that discriminate among specific syndromes may be absent (36).
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Behavioural and Physiological measures

The subjective experiences of pain and pain behaviours are, presumably, reflections of the same underlying neural processes. However, the complexity of the human brain indicates that although experience and behaviour are usually highly correlated, they are far from identical (26). Mistrust of verbal judgment has motivated the development of physiological and behavioural objective measures of pain. These are relatively insensitive to biasing factors and the psychological demands associated with requests for introspective reports (37). In addition, these methods are the only measures available for pain assessment in animals and in infants or in adults with poorly developed language skills. The behavioural measures to assess magnitude of stimulus-evoked pain sensation include the naturally occurring reactions (Grimace, vocalization, licking, limping, and rubbing) and trained operant behaviours (manipulating a bar to escape a painful stimulus). Recently facial expression evoked by experimental stimulation (38) or analysis of pain expression from photographs (39) has also been used.

There is a search for a physiological pain measure more objective than verbal report. Profound physiological changes often accompany the experience of pain, especially if the injury or noxious stimulus is acute (40). Autonomic measures such as heart rate, skin conductance and temperature have been correlated with pain stimulation. Although influenced by painful stimulation, these responses habituate quickly and respond nonspecifically (41). Measures of cortical-evoked potentials have been studied extensively and correlate with both stimulus intensity and verbal report. Cortical activity has also been assessed recently by analysis of noncontingent electroencephalogram (EEG) (42) and by nuclear magnetic resonance (NMR) techniques (43). Willer and others (44, 45) have used measures of reflex activity (e.g. blink, H and nociceptive reflexes) as objective measures of pain sensation.  Neurophysiological recording methods commonly employed in animal research have been used to investigate peripheral mechanisms in unanaesthetized normal volunteers (46). Human microneurography is powerful tool. This technique can identify all classes of primary afferent fibers and have verified the association of specific sensations with type of fiber stimulated (47). More effective pain measurement may ultimately result from an approach that integrates information from these separate, yet complementary sources of information (48, 49).
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Electroencephalography

A quantification of effects of experimental pain upon the spontaneous EEG of health volunteers by analysis of power spectral density (PSD) after Fourier transformation has been performed by many workers (42).  The quantitative methods in the study EEG have shown great increase in the use of research and clinical evaluation of pain in patients.  The use of experimental pain stimulus in association with EEG recording permits non-invasive investigation of the functional integrity of the nociceptive system in animals and humans. It has a great utility during pain, analgesic therapy and anesthesia. By this technique noxious stimulus of both brief phasic pain activation and longer diffuse type of tonic pain activation have been examined.  The heightened delta activity may reflect the stress component of human pain responsivity and that beta activity reflects the vigilance scanning of pain processes.  After intracutaneous noxious electrical stimulation, the stimulus-induced increase of power is mainly in low frequencies, delta and theta (42). Luque et al (50) studied power spectrum estimates of brain activity in chronic upper extremity pain patients and their result showed a diffuse asymmetry and cerebral activity for one half of the patients during intense, unilateral pain in contrast to non-pain states.  We have also conducted a series of power spectral studies (PSA) in normal controls, frostbite and chronic low backache patients. Our preliminary and unpublished results also indicate a heightened delta activity during pain state.

From reviewing the result of several studies in the CPS analysis of experimental pain and clinical pain patients, the EEG spectral power of low frequencies in delta and theta activities is often found to be associated with human pain. Some of the experimental studies also indicate that these power densities are sensitive to analgesic modulations (51). The difference among these studies may be related to different pain stimuli and pain duration, as well as in the classification of the bandwidths. But the striking similarity was a decrease in alpha and increase in beta activity after pain. The second consistent effect of tonic experimental pain of EEG power spectra is an increase of beta activity. It may directly be related to the resynchronization of alpha being replaced by faster rhythms but the nature of EEG changes in clinical pain states is very difficult to relate perceptual, emotional or cognitive processes linked to pain itself.
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Pain evoked potentials

Evoked potentials (EPs) are stimulus or event related electrical signals of brain activity that may be recorded from the scalp when precisely controlled discrete stimuli are delivered significant correlation exists between late. EP components evoked by experimental pain stimuli and the induced pain sensation.  EPs can serve as indicators of perception at multiple levels. Pain related brain evoked potentials are recognized as an objective and quantitative test for evaluation of peripheral and central spinothalamic tract, thalamocortical projections and cortico-cortical circuit for pain processing.  Chen et al (42) identified the current sources dipoles in noxious information processing.

Topographically, the early components of somatosensory evoked responses reflect contralateral activation. However, the pain related late components (52) and ultralate components are distributed bilaterally in both hemispheres and exhibit maximum amplitude in the vertex. The late components are assumed to reflect secondary mechanisms of information processing, such as stimulus recognition, localization, estimation of stimulus intensity and painfulness and initiation of motor movements. Further analysis by Chen et al (42) on the consistency and reliability of the pain-related sources revealed that too pain related components are consistently found a negatively at 145 msecs and a positivity at 225 msecs. The initial components, correlates with stimulus intensity and appear to code information about intensity of the external stimulation. The latter components are closely related to the subjective estimation of pain intensity and seem to reflect association processes involved in evaluation of noxious stimulus. Findings of Chen et al (42) clearly support the hypothesis that the EP may serve as a measure of pain experience in humans. Their finding suggests that the late components of the EP waveform may reflect the cognitive aspects of dental pain perception in laboratory models. When analgesic interventions are introduced, subjective reports of pain intensity is reduced and EP components diminish accordingly. Zaslansky et al (53) suggested that the pain-EP reflects the emotional-motivational response to pain rather than the sensory-discriminative. Thus, it provides a useful neurophysiological tool for studying the emotions associated with pain.
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Event related potentials (ERP)

ERP are late potential, which occur in response to a task. P300 is one such candidate. It is a late endogenous positive event related potential, occurring approximately 300 msecs after the onset of novel stimulus or a stimulus that is perceived as important. The P300 has been demonstrated to be related to information processing of the stimulus. The changes in amplitude and the latency are dependent on presentation qualities of the stimulus. The recoding of long latency event related cerebral EPs have been used as an objective measure of cognitive functions and perception. These potentials are valuable and useful parameters for assessing a variety of cognitive abilities (54) and psychological process including expectancy, attention, search, discrimination, decision-making and memory.  P300 is a valuable tool and our preliminary work have shown that it can evaluate the cognitive and effective components of pain (55, 56, 57, 58). It is generally believed that P300 components is immune to the effect of stimulus factors because of its endogenous origin (59). But Papanicolaou et al (60) have shown that P300 latency, but not amplitude, decreased as stimulus intensity was increased for both the standard and target stimuli. Further Polich (61) reported changes in components wave forms with manipulation of frequency and intensity parameters. Sugg and Polich (62) found that P300 amplitude increase and peak latency decreased as stimulus intensity increased with stimulus frequency also affecting these outcomes. Thus, both P300 amplitude and latency are affected variation in stimulus factors, although virtually no systemic studies of intensive effects have been reported (63). Our unpublished work has shown a change P300 with increasing strength of stimulation in healthy subjects (64). We (65) have shown a significant increase in P300 latency patients suffering from pain as compared to age and sex matched controls. Our findings suggest that there are cognitive changes in chronic pain states. The cognitive blunting is reversible with analgesic intervention (66).

Contingent negative variation (CNV) a surface-negative slow potential recorded from human subjects during a fixed foreperiod of a warned reaction-time task (67). This electrical phenomenon of the brain has drawn the interest of many psychophysiologists because it reflects some psychological processes such as expectancy motivate attention and arousal. The CNV waveform depends primarily on psychological and to a lesser extent on physical proportion of the stimulus presentation. CNV can be used to evaluate the affective-motivational components pain. It is still unclear how brain processes emotionality and pain, what are interaction mechanisms of emotion and pain. We have shown that the slow brain potentials in the contingent negative variation (CNV) are found to be larger in the pain condition than that of the control (68, 69). When patients with chronic pain were studied (70) in the CNV paradigm, the appearance of contingent negative variation response was more marked. It was concluded that slow evoked potentials are sensitive to anxiety level and to pain perception in man. Rizo (71) have also shown the usefulness of this measure in the investigation of pain as a complex sensation. A number of recent studies have assessed the influence of baseline or induced mood on subjective and psychological responses to experimental stimulation. Baseline (72) and induced (73) anxiety have been shown to increase pain ratings to thermal or pressure pain ratings, while an experimentally induced depressive mood (induced by presentation of text with depressing themes) decreased tolerance to cold pressor pain (74). Pain memory processes have been investigated using experimental painful stimulation (75). These studies provide experimental examples of how the experience of chronic pain can exert subtle influence on cognitive processes and mood. Pain itself can also impair cognitive and psychomotor performance.

Pain is a personal, subjective experience influenced by cultural learning, the meaning of the situation, attention and other psychological variables. Approaches to the measurement of pain include verbal and numeric self-rating scales, behavioural observation scales and physiological responses. The complex nature of the experience of pain suggests that measurements from these domains may not always show high concordance. Further development and refinement of pain measurement techniques will be able to meet the challenge and lead to increasingly accurate tools with greater predictive powers.
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