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British Journal of Anaesthesia
BJA

The sensory and affective components of pain: are they differentially modifiable dimensions or inseparable aspects of a unitary experience? A systematic review

Open ArchivePublished:April 30, 2019DOI:https://doi.org/10.1016/j.bja.2019.03.033

      Abstract

      Background

      Pain is recognised to have both a sensory dimension (intensity) and an affective dimension (unpleasantness). Pain feels like a single unpleasant bodily experience, but investigations of human pain have long considered these two dimensions of pain to be separable and differentially modifiable. The evidence underpinning this separability and differential modifiability is seldom presented. We aimed to fill this gap by evaluating the current evidence base for whether or not the sensory and affective dimensions of pain can be selectively modulated using cognitive manipulations.

      Methods

      A rigorous systematic search, based on a priori search terms and consultation with field experts, yielded 4270 articles. A detailed screening process was based on the following recommendations: (i) evaluation of effectiveness; (ii) examination of methodological rigour, including each study having an a priori intention to cognitively modulate one of the two dimensions of pain; and (iii) sound theoretical reasoning. These were used to ensure that included studies definitively answered the research question.

      Results

      After in-depth critique of all 12 articles that met the inclusion criteria, we found that there is no compelling evidence that the sensory and affective dimensions of pain can be selectively and intentionally modulated using cognitive manipulations in humans.

      Conclusions

      We offer potential explanations for this discrepancy between assumptions and evidence and contend that this finding highlights several important questions for the field, from both the research and clinical perspectives.

      Keywords

      Pain commonly drives the sufferer towards safety; it can be considered a motivator of protective behaviour rather than a marker of tissue damage.
      • Moseley G.L.
      • Butler D.S.
      Fifteen years of explaining pain: the past, present, and future.
      • Moseley G.L.
      • Vlaeyen J.W.
      Beyond nociception: the imprecision hypothesis of chronic pain.
      The clear motivational drive of pain makes it more closely resemble feelings such as hunger or thirst than sensory perceptions such as vision or hearing.
      • Moseley G.L.
      Why do people with complex regional pain syndrome take longer to recognize their affected hand?.
      That pain is necessarily perceived—one cannot have pain and not know about it—and its inherent unpleasantness (or indeed its juxtaposition to pleasure) have occupied human thought for millennia: Plato wrote ‘ … All pleasure and pain come to be in the soul, because all pleasure and pain is necessarily perceived … ’.
      • Erginel M.M.
      Plato on the psychology of pleasure and pain.
      This immutable emotional nature of pain was recognised more formally, as one dimension of a wider pain experience, towards the end of the past century, with the proposal that pain is a bidimensional experience consisting of a sensory-discriminative dimension and an affective-motivational dimension.
      • Price D.
      Psychological and neural mechanisms of the affective dimension of pain.
      This is further highlighted through the International Association for the Study of Pain definition of pain as ‘[a]n unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage’.
      IASP. International Association for the Study of Pain IASP Terminology 2017
      The sensory-discriminative dimension, often referred to simply as ‘intensity’ or given the label ‘sensory’, includes the spatial, and temporal characteristics and quality of pain.
      • Auvray M.
      • Myin E.
      • Spence C.
      The sensory-discriminative and affective-motivational aspects of pain.
      The affective-motivational dimension, often referred to simply as ‘unpleasantness’ or given the label ‘affective’, captures how ‘bad’ or how ‘unpleasant’ the pain is.
      • Auvray M.
      • Myin E.
      • Spence C.
      The sensory-discriminative and affective-motivational aspects of pain.
      That is, it captures the motivational aspect of pain—the aspect that makes us want to take protective action.
      That pain is felt at a bodily location and therefore has sensory qualities, while also being definitively unpleasant, led to the development of the most widespread and tested pain assessment tool—the McGill Pain Questionnaire.
      • Melzack R.
      • Katz J.
      The McGill Pain Questionnaire: appraisal and current status.
      There is a large body of literature concerning the properties of the McGill Pain Questionnaire and recognisable patterns of responses that can differentiate between, for example, neuropathic and non-neuropathic pain.
      • Treede R.-D.
      The International Association for the Study of Pain definition of pain: as valid in 2018 as in 1979, but in need of regularly updated footnotes.
      This potentially separable bidimensionality of pain is apparent in some clinical studies. For example, people who attribute their pain to a greater threat to their health will rate the pain unpleasantness higher than those who attribute their pain to a lesser threat to their health, despite having similar self-reported pain intensities.
      • Taenzer P.
      • Melzack R.
      • Jeans M.E.
      Influence of psychological factors on postoperative pain, mood and analgesic requirements.
      • Wade J.B.
      • Price D.
      • Hamer R.M.
      • Schwartz S.M.
      • Hart R.P.
      An emotional component analysis of chronic pain.
      Cognitive manipulations during brain imaging have been used to tease apart the cortical activation patterns associated with the sensory and affective dimensions of pain.
      • Maihofner C.
      • Herzner B.
      • Handwerker H.
      Secondary somatosensory cortex is important for the sensory-discriminative dimension of pain: a functional MRI study.
      • Rainville P.
      Brain mechanisms of pain affect and pain modulation.
      Study reports implicate the anterior cingulate cortex (ACC) in subserving pain unpleasantness in particular.
      • Rainville P.
      • Feine J.S.
      • Bushnell M.
      • Duncan G.H.
      A psychophysical comparison of sensory and affective responses to four modalities of experimental pain.
      For example, a cognitive manipulation to increase the affective dimension of pain (i.e. to make it more unpleasant but not more ‘intense’) caused an increase in ACC activation; a cognitive manipulation to decrease the affective dimension (i.e. make it less unpleasant but no less intense) caused a decrease in ACC activation.
      • Rainville P.
      • Feine J.S.
      • Bushnell M.
      • Duncan G.H.
      A psychophysical comparison of sensory and affective responses to four modalities of experimental pain.
      Similar direction-specific modulation of the primary somatosensory cortex (S1) was reported in conjunction with manipulation of the sensory dimension of pain.
      • Rainville P.
      • Feine J.S.
      • Bushnell M.
      • Duncan G.H.
      A psychophysical comparison of sensory and affective responses to four modalities of experimental pain.
      Functional neuroanatomical data have also been used to substantiate the claim that these two dimensions of pain involve distinct neural pathways from the dorsal horn of the spinal cord to cortical centres (see Treede and colleagues
      • Treede R.-D.
      • Kenshalo D.R.
      • Gracely R.H.
      • Jones A.K.
      The cortical representation of pain.
      for further details).
      • Price D.
      Central neural mechanisms that interrelate sensory and affective dimensions of pain.
      The lateral spinothalamic pathway has been proposed to subserve the sensory dimension of pain, because of the type of synaptic input and main cerebral projection.
      • Price D.
      Central neural mechanisms that interrelate sensory and affective dimensions of pain.
      Strengthening this proposition is the finding that nociceptive neurones within the spinothalamic pathway are predominantly wide dynamic range (WDR) neurones, which by definition are responsive to a wide range of stimuli, from light touch to intense stimulation.
      • Coghill R.C.
      • Mayer D.J.
      • Price D.
      Wide dynamic range but not nociceptive-specific neurons encode multidimensional features of prolonged repetitive heat pain.
      The spino-parabrachio-amygdaloid and spino-parabrachio-hypothalamic have been proposed to subserve the affective dimension of pain,
      • Coghill R.C.
      • Mayer D.J.
      • Price D.
      Wide dynamic range but not nociceptive-specific neurons encode multidimensional features of prolonged repetitive heat pain.
      • Willis W.
      • Zhang X.
      • Honda C.
      • Giesler G.J.
      Projections from the marginal zone and deep dorsal horn to the ventrobasal nuclei of the primate thalamus.
      largely because they comprise mainly nociceptive neurones and their central projections terminate in the amygdala and hypothalamus, which are thought to play a role in fear, emotional memory and behaviour, and autonomic and somatomotor responses to threatening stimuli.
      • Willis W.
      • Westlund K.
      Neuroanatomy of the pain system and of the pathways that modulate pain.
      Many neurophysiologists, neuroanatomists, and pain researchers seem accepting of these ideas, but other specialists have argued that pain is in fact an unidimensional construct and that separating it into dimensions is as fallacious as attributing it to single neurones.
      • Smart K.
      • Doody C.
      Mechanisms-based clinical reasoning of pain by experienced musculoskeletal physiotherapists.
      The latter group argue that the apparently successful attempts to independently modulate the two dimensions of pain via cognitive strategies—for example, in the imaging studies mentioned earlier—actually reflect demand effects (or the effects of ‘coaching’ participants), not selective endogenous modulation of pain's two dimensions.
      • Chapman R.
      • Nakamura Y.
      • Donaldson G.W.
      • et al.
      Sensory and affective dimensions of phasic pain are indistinguishable in the self-report and psychophysiology of normal laboratory subjects.
      Indeed, whether people can even differentiate the two dimensions remains contentious. Several studies have shown that participants tend to rate the sensory and affective dimensions of pain similarly, unless they receive clear instructions that explicitly highlight differences between them.
      • Fernandez E.
      • Turk D.C.
      Demand characteristics underlying differential ratings of sensory versus affective components of pain.
      • Chapman R.
      Limbic processes and the affective dimension of pain.
      • Chapman R.
      • Donaldson G.W.
      • Nakamura Y.
      • Jacobson R.C.
      • Bradshaw D.H.
      • Gavrin J.
      A psychophysiological causal model of pain report validity.
      When such a fundamental matter is soundly endorsed by some parts of the community (predominantly scientists) and soundly rejected by others (predominantly clinicians, philosophers, and laypeople), one might expect the evidence for either position to be clearly presented.
      • Rainville P.
      Brain mechanisms of pain affect and pain modulation.
      • Rainville P.
      • Feine J.S.
      • Bushnell M.
      • Duncan G.H.
      A psychophysical comparison of sensory and affective responses to four modalities of experimental pain.
      • Fledman J.
      Expanding hypnotic pain management the affective dimension of pain.
      • Younger J.
      • McCue R.
      • Mackey S.
      Pain outcomes: a brief review of instruments and techniques.
      However, there seems to have been very little attempt to evaluate the actual evidence for either view. This is surprising because experimental studies continue to differentiate them, whereas clinical practice continues to consider pain a single construct—patients are almost always asked ‘How is your pain?’. Within the context of the lived experience of pain and the position it takes within social interactions, we might ask ‘How bad is it?’, or ‘Where is it?’, but such questions consider pain as a unitary unpleasant sensory experience that affects that person.
      • Wittgenstein L.
      • von Wright G.
      Wittgenstein's nachlass the bergen.
      By failing to evaluate the actual evidence for whether the separation and independent modulation of the sensory and affective dimensions of pain is possible, studies, clinical interactions, and treatment development based on either viewpoint, remain questionable.
      We systematically evaluated the evidence that the two dimensions of pain can be selectively modulated in humans using a cognitive manipulation. Our approach was informed by the seminal review in this field, which also remains the most recent.
      • Fernandez E.
      • Turk D.C.
      Sensory and affective components of pain: separation and synthesis.
      That work concluded that, in order to address the contention that threatened to polarise the field, there needed to be (i) a comprehensive evaluation of the effectiveness of attempts to modulate the two postulated dimensions of pain; (ii) a structured framework and standardised appraisal to examine the methodological rigour of each study, including the potential threats to validity of uncontrolled biases, with each included study having an a priori intention to use a cognitive strategy to selectively modulate one of the two dimensions of pain; and (iii) that all such investigations are planned according to sound theoretical reasoning.

      Methods

      For the review, the following PICO (Population, Intervention, Comparison, and Outcome) question was devised (see Table 1).
      Table 1PICO question.
      PopulationInterventionComparisonOutcome
      People with chronic pain and healthy volunteersCognitive manipulationsNoneThe extent to which the affective and sensory dimensions of pain can be selectively and intentionally modulated
      This systematic review was carried out following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and an a priori protocol based on the recommendations of Fernandez and Turk
      • Fernandez E.
      • Turk D.C.
      Sensory and affective components of pain: separation and synthesis.
      (see Supplementary File 1).
      • Moher D.
      • Liberati A.
      • Tetzlaff J.
      • Altman D.G.
      PRISMA Group
      Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.

       Information sources

      The following databases were searched from their inception to February 2017: Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; MEDLINE (OvidSP); SciVerse SCOPUS; PsycINFO (OvidSP); and Embase classic and Embase (OvidSP). A sensitive search strategy was devised, using a combination of keywords, relevant subject headings and MeSH terms. The aim was to identify studies that investigated the selective cognitive modulation of the sensory and affective dimensions of pain. The initial search strategy was developed in Medline (OvidSP), and then adapted for other databases (see Supplementary File 2).

       Search

       Study selection

      The titles and abstracts of all records that were identified by the initial search were independently screened and evaluated, using a predetermined list of inclusion criteria, by two reviewers (KAT and VJM). Studies were included if they met all of the following criteria: tested human participants; applied a cognitive technique with the aim of selectively modulating either the sensory or the affective dimension of pain; followed an experimental study design that had at least one of the following: measured a baseline, had a control group, had a pre–post design; assessed both the sensory and affective dimensions. Studies were excluded if they used somatosensory (e.g. transcutaneous electrical nerve stimulation) or exogenous pharmacological (e.g. morphine) interventions to modulate pain. Studies could include participants with acute pain, chronic pain, or no pain, in which case the study would involve experimentally induced pain. Where more than one participant group was included, the groups were evaluated separately. The search was not limited by language, but the title and abstract had to be in English to allow for initial assessment of eligibility. Full texts were retrieved for all eligible records, and independently appraised by two reviewers (KAT and VJM). Non-English full-text articles that were identified as potentially eligible were translated by two independent translators before assessment.

       Risk of bias across studies

      We developed, tested, and refined a customised risk of bias tool (see Supplementary File 3). This tool was then applied by two independent reviewers (KAT and VJM) to all included studies. For each category of risk, the reviewers highlighted particular factors that could be sources of bias. Minimum criteria were defined for a low risk of bias rating in certain categories. Studies were expected to have confirmed the efficacy of the cognitive manipulation by reporting the results of the manipulation check and reporting the efficacy of participant blinding. Outcome measures were expected to be clearly assessing pain rather than the stimulus. Purposive or convenience sampling were considered to introduce high risk of bias (a deliberately conservative decision although we recognise that, for pragmatic reasons, most research in this field uses convenience sampling).

       Data collection process

      Data extraction was performed by two independent reviewers (KAT and VJM) using a customised and pre-piloted form (see Supplementary File 4). Extracted data were: participant characteristics such as age and gender, study methods, trial characteristics, and details of the outcome measures.

       Outcome measures

      The primary outcomes were participant ratings of the sensory and affective dimensions of the experiences that were evoked by painful stimuli. The secondary outcomes were differences in cortical activation, physiological responses, and psychological variables associated with the manipulations. We summarised data by subtracting the change in the ‘non-target’ dimension from the change in the ‘target’ dimension, producing a mean difference (and standard error of the mean difference) as an estimate of the manipulation's effectiveness. Mean and standard error (se) data were then entered in to Review Manager (version 5.2, The Nordic Cochrane Centre, Copenhagen, Denmark) using the generic inverse function and pooled using the random-effects model. For full details, see Supplementary File 5.

      Results

       Study selection

      The initial search and removal of duplicates yielded 4708 records. After the screening phase, 232 full-text articles were assessed for eligibility. Two records were reviewed with the help of translators. After assessment of eligibility, 12 articles were included in this systematic review. The details of identification, screening, and appraisal are depicted in Figure 1.
      Fig. 1
      Fig 1PRISMA flowchart of systematic search strategy. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

       Study characteristics

      Five studies used hypnotic induction with suggestion (n=5),
      • Rainville P.
      • Duncan G.
      • Price D.
      • Carrier B.
      • Bushnell M.C.
      Pain affect encoded in human anterior cingulate but not somatosensory cortex.
      • Rainville P.
      • Carrier B.
      • Hofbauer R.K.
      • Bushnell M.C.
      • Duncan G.H.
      Dissociation of sensory and affective dimensions of pain using hypnotic modulation.
      • Hofbauer R.
      • Rainville P.
      • Duncan G.
      • Bushnell M.C.
      Cortical representation of the sensory dimension of pain.
      • Dahlgren L.A.
      • Kurtz R.M.
      • Strube M.J.
      • Malone M.D.
      Differential effects of hypnotic suggestion on multiple dimensions of pain.
      • Valentini E.
      • Betti V.
      • Hu L.
      colleagues
      Hypnotic modulation of pain perception and of brain activity triggered by nociceptive laser stimuli.
      one used suggestion alone (without hypnotic induction; n=1),
      • Kunz M.
      • Lautenbacher S.
      • LeBlanc N.
      • Rainville P.
      Are both the sensory and the affective dimensions of pain encoded in the face?.
      four used valence modulation secondary to odour (n=1)
      • Rainville P.
      Brain mechanisms of pain affect and pain modulation.
      • Rainville P.
      • Feine J.S.
      • Bushnell M.
      • Duncan G.H.
      A psychophysical comparison of sensory and affective responses to four modalities of experimental pain.
      • Fledman J.
      Expanding hypnotic pain management the affective dimension of pain.
      • Younger J.
      • McCue R.
      • Mackey S.
      Pain outcomes: a brief review of instruments and techniques.
      or visual images (n=3),
      • Kenntner-Mabiala R.
      • Weyers P.
      • Pauli P.
      Independent effects of emotion and attention on sensory and affective pain perception.
      • Kenntner-Mabiala R.
      • Andreatta M.
      • Wieser M.J.
      • Muhlberger A.
      • Pauli P.
      Distinct effects of attention and affect on pain perception and somatosensory evoked potentials.
      • Loggia M.L.
      • Mogil J.S.
      • Bushnell M.
      Experimentally induced mood changes preferentially affect pain unpleasantness.
      and two used meditation (n=2)
      • Perlman D.M.
      • Salomons T.V.
      • Davidson R.J.
      • Lutz A.
      Differential effects on pain intensity and unpleasantness of two meditation practices.
      • Grant J.A.
      • Rainville P.
      Pain sensitivity and analgesic effects of mindful states in Zen meditators: a cross-sectional study.
      (Table 2). Although some manipulations were similar, comparability was limited because even studies that used the same class of manipulation used different methods. For example, although Dahlgren and colleagues
      • Dahlgren L.A.
      • Kurtz R.M.
      • Strube M.J.
      • Malone M.D.
      Differential effects of hypnotic suggestion on multiple dimensions of pain.
      and Rainville and colleagues
      • Rainville P.
      • Duncan G.
      • Price D.
      • Carrier B.
      • Bushnell M.C.
      Pain affect encoded in human anterior cingulate but not somatosensory cortex.
      used hypnotic suggestion, Dahlgren and colleagues
      • Dahlgren L.A.
      • Kurtz R.M.
      • Strube M.J.
      • Malone M.D.
      Differential effects of hypnotic suggestion on multiple dimensions of pain.
      targeted intensity and unpleasantness using different suggestions, whereas Rainville and colleagues
      • Rainville P.
      • Duncan G.
      • Price D.
      • Carrier B.
      • Bushnell M.C.
      Pain affect encoded in human anterior cingulate but not somatosensory cortex.
      targeted unpleasantness only, using different suggestions to elicit either an increase or a decrease in unpleasantness.
      Table 2Key characteristic summary of articles. *Unclear in manuscript/unable to obtain further information. INT, pain intensity; MES, Magnitude Estimation Scale; N/R, not reported; NRS: Numeric Rating Scale; PL, pleasant; UNP, pain unpleasantness; VRS, Verbal Rating Scale.
      First authorYearSample size, n (F:M)Mean age, yr (age range)Cognitive manipulationScale typeSensory pain anchors (pain intensity)Affective pain anchors (pain unpleasantness)
      Hypnotic induction with suggestion
      Dahlgren
      • Dahlgren L.A.
      • Kurtz R.M.
      • Strube M.J.
      • Malone M.D.
      Differential effects of hypnotic suggestion on multiple dimensions of pain.
      199532 (17:15)N/R*Hypnotic Suggestion for relaxation or analgesiaVRSSensory list of wordsAffective list of words
      Rainville
      • Rainville P.
      • Duncan G.
      • Price D.
      • Carrier B.
      • Bushnell M.C.
      Pain affect encoded in human anterior cingulate but not somatosensory cortex.
      19978 (3:5)19–53 yrHypnotic Suggestion to ↓ and ↑ pain UNPNRS0: No burning, pricking, stinging sensation0: Not at all UNP
      100: Extremely intense sensation100: Extremely UNP
      Rainville
      • Rainville P.
      • Carrier B.
      • Hofbauer R.K.
      • Bushnell M.C.
      • Duncan G.H.
      Dissociation of sensory and affective dimensions of pain using hypnotic modulation.
      1999Exp 1:17 (5:12)Exp 1: 17–28

      Controls: 19–21
      Exp 1: Hypnotic suggestion to ↓ pain UNPVASBurning, pricking, stinging sensationN/R*
      Exp 2: 20 (7:13)Exp 2: 18–37Exp 2: Hypnotic suggestion to ↓ ↑ pain UNP
      Exp 3: 22 (10:12)Exp 3: 20–29Exp 3: Hypnotic suggestion to ↓ and ↑ pain INT
      Hofbauer
      • Hofbauer R.
      • Rainville P.
      • Duncan G.
      • Bushnell M.C.
      Cortical representation of the sensory dimension of pain.
      200110 (6:4)20–35Hypnotic suggestion to ↓ and ↑ pain INTMESN/R*N/R*
      Valentini
      • Valentini E.
      • Betti V.
      • Hu L.
      colleagues
      Hypnotic modulation of pain perception and of brain activity triggered by nociceptive laser stimuli.
      201324 (24:0)20–25Hypnotic suggestion to alter pain INT or UNPVAS0: No pricking/burning/itching0: Not at all UNP
      101: Intolerable intensity101: Intolerable UNP
      Meditation
      Perlman
      • Perlman D.M.
      • Salomons T.V.
      • Davidson R.J.
      • Lutz A.
      Differential effects on pain intensity and unpleasantness of two meditation practices.
      201019 (9:10)Experimental: 37–59MeditationNRSN/R*N/R*
      Controls: 35–59
      Grant
      • Grant J.A.
      • Rainville P.
      Pain sensitivity and analgesic effects of mindful states in Zen meditators: a cross-sectional study.
      200928 (10:18)Experimental: 23–47MeditationVAS0: Not painful0: Not UNP
      Controls: 24–4510: Extremely painful10: Extremely UNP
      Valence induction with exteroceptive stimuli
      Kenntner-Mabiala
      • Kenntner-Mabiala R.
      • Weyers P.
      • Pauli P.
      Independent effects of emotion and attention on sensory and affective pain perception.
      200754 (27:27)18–40Picture valence and attentionVAS0: No pressure–100: Very UNP
      100: Just noticeable p100: Very PL
      200: Unbearable p
      Kenntner-Mabiala
      • Kenntner-Mabiala R.
      • Andreatta M.
      • Wieser M.J.
      • Muhlberger A.
      • Pauli P.
      Distinct effects of attention and affect on pain perception and somatosensory evoked potentials.
      200830 (15:15)21–36Picture valence and attentionVAS*0: No sensation0: Neutral
      4: Just noticeable pain10: Very UNP
      10: Unbearable pain
      Loggia
      • Loggia M.L.
      • Mogil J.S.
      • Bushnell M.
      Experimentally induced mood changes preferentially affect pain unpleasantness.
      200812 (12:0)47–55Video valenceNRS0: No heatN/R*
      200: Most intense pain tolerable
      Villemure
      • Villemure C.
      • Slotnick B.M.
      • Bushnell M.
      Effects of odors on pain perception: deciphering the roles of emotion and attention.
      200314 (9:5)20–26Odour and attentionNRS0: No pain0: Neutral
      10: Most intense pain tolerable10: Extremely UNP
      Suggestion alone
      Kunz
      • Kunz M.
      • Lautenbacher S.
      • LeBlanc N.
      • Rainville P.
      Are both the sensory and the affective dimensions of pain encoded in the face?.
      201222 (10:12)18–27Suggestion to ↑ pain UNP or INTVAS0: No pain0: No pain
      100: Extremely strong pain100: Extremely UNP pain
      All the included studies used healthy, pain-free, adult participants. That is, there were no studies that satisfied our a priori criteria and included people with acute or chronic clinical pain. All included studies had biased eligibility criteria. All five hypnosis studies selectively recruited participants with certain susceptibility profiles: four recruited participants who had moderate to high scores of susceptibility
      • Rainville P.
      • Duncan G.
      • Price D.
      • Carrier B.
      • Bushnell M.C.
      Pain affect encoded in human anterior cingulate but not somatosensory cortex.
      • Rainville P.
      • Carrier B.
      • Hofbauer R.K.
      • Bushnell M.C.
      • Duncan G.H.
      Dissociation of sensory and affective dimensions of pain using hypnotic modulation.
      • Hofbauer R.
      • Rainville P.
      • Duncan G.
      • Bushnell M.C.
      Cortical representation of the sensory dimension of pain.
      • Dahlgren L.A.
      • Kurtz R.M.
      • Strube M.J.
      • Malone M.D.
      Differential effects of hypnotic suggestion on multiple dimensions of pain.
      ; one recruited two groups—one group of people who had high scores of susceptibility and another group of people who had low scores of susceptibility.
      • Valentini E.
      • Betti V.
      • Hu L.
      colleagues
      Hypnotic modulation of pain perception and of brain activity triggered by nociceptive laser stimuli.
      Both meditation studies recruited a group of expert meditators who had spent a set number of hours in meditative practice, and a group of novices.
      • Perlman D.M.
      • Salomons T.V.
      • Davidson R.J.
      • Lutz A.
      Differential effects on pain intensity and unpleasantness of two meditation practices.
      • Grant J.A.
      • Rainville P.
      Pain sensitivity and analgesic effects of mindful states in Zen meditators: a cross-sectional study.
      Several studies included only participants who had demonstrated successful attentional or emotional modulation of pain during recruitment.
      • Hofbauer R.
      • Rainville P.
      • Duncan G.
      • Bushnell M.C.
      Cortical representation of the sensory dimension of pain.
      • Kunz M.
      • Lautenbacher S.
      • LeBlanc N.
      • Rainville P.
      Are both the sensory and the affective dimensions of pain encoded in the face?.
      • Villemure C.
      • Slotnick B.M.
      • Bushnell M.
      Effects of odors on pain perception: deciphering the roles of emotion and attention.
      Overall, there were more female participants (n=164) than male participants (n=148). Two studies recruited only female participants.
      • Valentini E.
      • Betti V.
      • Hu L.
      colleagues
      Hypnotic modulation of pain perception and of brain activity triggered by nociceptive laser stimuli.
      • Loggia M.L.
      • Mogil J.S.
      • Bushnell M.
      Experimentally induced mood changes preferentially affect pain unpleasantness.

       Risk of bias within studies

      All studies were at high risk of selection, performance, or detection bias, or failed to provide sufficient data for us to assess risk of bias (Table 3). The most common reasons for studies to be scored as ‘high risk’ in the selection bias section were selective recruitment or convenience sampling. Full data for risk of bias are presented in Table 3 and in Supplementary File 5.
      Table 3Risk of bias assessment of included studies. ×, high bias; ✓, low bias; ?, unclear (unclear in manuscript/unable to obtain further information).
      First author (year)Selection biasPerformance and detection biasCognitive techniqueMeasurement biasStatistical methodsReporting
      Hypnotic induction with suggestion
       Dahlgren (1995)
      • Dahlgren L.A.
      • Kurtz R.M.
      • Strube M.J.
      • Malone M.D.
      Differential effects of hypnotic suggestion on multiple dimensions of pain.
      ×?××
       Rainville (1997)
      • Rainville P.
      • Duncan G.
      • Price D.
      • Carrier B.
      • Bushnell M.C.
      Pain affect encoded in human anterior cingulate but not somatosensory cortex.
      ×××??×
       Rainville (1999)
      • Rainville P.
      • Carrier B.
      • Hofbauer R.K.
      • Bushnell M.C.
      • Duncan G.H.
      Dissociation of sensory and affective dimensions of pain using hypnotic modulation.
      ×?××
       Hofbauer (2001)
      • Hofbauer R.
      • Rainville P.
      • Duncan G.
      • Bushnell M.C.
      Cortical representation of the sensory dimension of pain.
      ××××
       Valentini (2013)
      • Valentini E.
      • Betti V.
      • Hu L.
      colleagues
      Hypnotic modulation of pain perception and of brain activity triggered by nociceptive laser stimuli.
      ×××
      Meditation
       Grant (2009)
      • Grant J.A.
      • Rainville P.
      Pain sensitivity and analgesic effects of mindful states in Zen meditators: a cross-sectional study.
      ×××
       Perlman (2010)
      • Perlman D.M.
      • Salomons T.V.
      • Davidson R.J.
      • Lutz A.
      Differential effects on pain intensity and unpleasantness of two meditation practices.
      ×?×××
      Valence induction with exteroceptive stimuli
       Kenntner-Mabiala (2007)
      • Kenntner-Mabiala R.
      • Weyers P.
      • Pauli P.
      Independent effects of emotion and attention on sensory and affective pain perception.
      ×?×
       Kenntner-Mabiala (2008)
      • Kenntner-Mabiala R.
      • Andreatta M.
      • Wieser M.J.
      • Muhlberger A.
      • Pauli P.
      Distinct effects of attention and affect on pain perception and somatosensory evoked potentials.
      ??×
       Loggia (2008)
      • Loggia M.L.
      • Mogil J.S.
      • Bushnell M.
      Experimentally induced mood changes preferentially affect pain unpleasantness.
      ×?×
       Villemure (2003)
      • Villemure C.
      • Slotnick B.M.
      • Bushnell M.
      Effects of odors on pain perception: deciphering the roles of emotion and attention.
      ×?
      Suggestion alone
      Kunz (2012)
      • Kunz M.
      • Lautenbacher S.
      • LeBlanc N.
      • Rainville P.
      Are both the sensory and the affective dimensions of pain encoded in the face?.
      ×××

       Results of individual studies

       Hypnosis induction with suggestion

      Five studies used hypnotic induction with suggestion. Four of the five studies found that hypnotic suggestion selectively increased or decreased affective dimension ratings in accordance with the type of suggestions given.
      • Rainville P.
      • Duncan G.
      • Price D.
      • Carrier B.
      • Bushnell M.C.
      Pain affect encoded in human anterior cingulate but not somatosensory cortex.
      • Rainville P.
      • Carrier B.
      • Hofbauer R.K.
      • Bushnell M.C.
      • Duncan G.H.
      Dissociation of sensory and affective dimensions of pain using hypnotic modulation.
      • Dahlgren L.A.
      • Kurtz R.M.
      • Strube M.J.
      • Malone M.D.
      Differential effects of hypnotic suggestion on multiple dimensions of pain.
      • Valentini E.
      • Betti V.
      • Hu L.
      colleagues
      Hypnotic modulation of pain perception and of brain activity triggered by nociceptive laser stimuli.
      However, they were unable to demonstrate the same effect with the sensory dimension ratings. The three studies that also aimed to selectively modulate the sensory dimension of pain did not achieve selective modulation.
      • Rainville P.
      • Carrier B.
      • Hofbauer R.K.
      • Bushnell M.C.
      • Duncan G.H.
      Dissociation of sensory and affective dimensions of pain using hypnotic modulation.
      • Hofbauer R.
      • Rainville P.
      • Duncan G.
      • Bushnell M.C.
      Cortical representation of the sensory dimension of pain.
      • Valentini E.
      • Betti V.
      • Hu L.
      colleagues
      Hypnotic modulation of pain perception and of brain activity triggered by nociceptive laser stimuli.
      Interestingly, the reported changes in cortical activation patterns did not match participant pain reports: when hypnotic suggestion targeted the sensory dimension, there was no evidence of selective change in ratings of the sensory or affective dimensions of pain, but there was evidence of selective activation of cortical areas.
      • Rainville P.
      • Carrier B.
      • Hofbauer R.K.
      • Bushnell M.C.
      • Duncan G.H.
      Dissociation of sensory and affective dimensions of pain using hypnotic modulation.
      • Hofbauer R.
      • Rainville P.
      • Duncan G.
      • Bushnell M.C.
      Cortical representation of the sensory dimension of pain.
      • Valentini E.
      • Betti V.
      • Hu L.
      colleagues
      Hypnotic modulation of pain perception and of brain activity triggered by nociceptive laser stimuli.
      Suggestions that intended to modulate the sensory dimension of pain selectively altered cortical activation in the somatosensory areas (S1 and S2), whereas suggestions that intended to modulate the affective dimension of pain selectively altered ACC activation. The fifth hypnosis study found that hypnosis with suggestion of analgesia selectively decreased ratings of the sensory dimension, whereas hypnosis with suggestion of relaxation selectively decreased the affective dimension of pain.
      • Dahlgren L.A.
      • Kurtz R.M.
      • Strube M.J.
      • Malone M.D.
      Differential effects of hypnotic suggestion on multiple dimensions of pain.
      Another factor that influenced the effect of the selective modulation was the hypnotic susceptibility of the participants. Three of the studies reported that participants with high susceptibility to hypnosis demonstrated greater selective modulation of the two dimensions than participants with low susceptibility.
      • Rainville P.
      • Carrier B.
      • Hofbauer R.K.
      • Bushnell M.C.
      • Duncan G.H.
      Dissociation of sensory and affective dimensions of pain using hypnotic modulation.
      • Hofbauer R.
      • Rainville P.
      • Duncan G.
      • Bushnell M.C.
      Cortical representation of the sensory dimension of pain.
      • Valentini E.
      • Betti V.
      • Hu L.
      colleagues
      Hypnotic modulation of pain perception and of brain activity triggered by nociceptive laser stimuli.

       Suggestion alone (without hypnotic induction)

      The only study that used non-hypnotic suggestion found that both dimensions of pain could be selectively modulated, depending on the type of suggestion that was given.
      • Kunz M.
      • Lautenbacher S.
      • LeBlanc N.
      • Rainville P.
      Are both the sensory and the affective dimensions of pain encoded in the face?.
      That is, suggestions to decrease the sensory dimension of pain resulted in lower pain intensity but not pain unpleasantness ratings, and vice versa.

       Valence modulation using exteroceptive stimuli

      Four studies used exteroceptive stimuli to modulate valence, and tested the effect of the modulation of valence on separate dimensions.
      • Villemure C.
      • Slotnick B.M.
      • Bushnell M.
      Effects of odors on pain perception: deciphering the roles of emotion and attention.
      • Kenntner-Mabiala R.
      • Weyers P.
      • Pauli P.
      Independent effects of emotion and attention on sensory and affective pain perception.
      • Kenntner-Mabiala R.
      • Andreatta M.
      • Wieser M.J.
      • Muhlberger A.
      • Pauli P.
      Distinct effects of attention and affect on pain perception and somatosensory evoked potentials.
      • Loggia M.L.
      • Mogil J.S.
      • Bushnell M.
      Experimentally induced mood changes preferentially affect pain unpleasantness.
      Three of the four studies reported selective modulation of affective dimension ratings,
      • Villemure C.
      • Slotnick B.M.
      • Bushnell M.
      Effects of odors on pain perception: deciphering the roles of emotion and attention.
      • Kenntner-Mabiala R.
      • Andreatta M.
      • Wieser M.J.
      • Muhlberger A.
      • Pauli P.
      Distinct effects of attention and affect on pain perception and somatosensory evoked potentials.
      • Loggia M.L.
      • Mogil J.S.
      • Bushnell M.
      Experimentally induced mood changes preferentially affect pain unpleasantness.
      and one reported similar shifts in both sensory and affective dimension ratings
      • Kenntner-Mabiala R.
      • Weyers P.
      • Pauli P.
      Independent effects of emotion and attention on sensory and affective pain perception.
      ; three manipulated participants' attention
      • Kenntner-Mabiala R.
      • Weyers P.
      • Pauli P.
      Independent effects of emotion and attention on sensory and affective pain perception.
      • Kenntner-Mabiala R.
      • Andreatta M.
      • Wieser M.J.
      • Muhlberger A.
      • Pauli P.
      Distinct effects of attention and affect on pain perception and somatosensory evoked potentials.
      • Loggia M.L.
      • Mogil J.S.
      • Bushnell M.
      Experimentally induced mood changes preferentially affect pain unpleasantness.
      ; two used a three-way manipulation in which participants were tasked with directing their attention ‘towards the pictures’, ‘towards the sensory experience’, or ‘towards the affective experience’
      • Kenntner-Mabiala R.
      • Weyers P.
      • Pauli P.
      Independent effects of emotion and attention on sensory and affective pain perception.
      • Kenntner-Mabiala R.
      • Andreatta M.
      • Wieser M.J.
      • Muhlberger A.
      • Pauli P.
      Distinct effects of attention and affect on pain perception and somatosensory evoked potentials.
      ; one used a two-way manipulation in which participants attended to either heat or an odour.
      • Villemure C.
      • Slotnick B.M.
      • Bushnell M.
      Effects of odors on pain perception: deciphering the roles of emotion and attention.
      Interestingly, in the two studies by Kenntner-Mabiala and colleagues,
      • Kenntner-Mabiala R.
      • Weyers P.
      • Pauli P.
      Independent effects of emotion and attention on sensory and affective pain perception.
      • Kenntner-Mabiala R.
      • Andreatta M.
      • Wieser M.J.
      • Muhlberger A.
      • Pauli P.
      Distinct effects of attention and affect on pain perception and somatosensory evoked potentials.
      only sensory ratings changed, but the first study involved attention to the sensory experience and the second study involve attention to the affective experience.

       Meditation

      Two studies compared the modulatory effects of two meditation techniques; one focused on attention,
      • Grant J.A.
      • Rainville P.
      Pain sensitivity and analgesic effects of mindful states in Zen meditators: a cross-sectional study.
      and the other on acceptance, sometimes referred to as ‘open monitoring’.
      • Perlman D.M.
      • Salomons T.V.
      • Davidson R.J.
      • Lutz A.
      Differential effects on pain intensity and unpleasantness of two meditation practices.
      When performed by experienced meditators, acceptance-based meditation selectively modulated unpleasantness in one study,
      • Perlman D.M.
      • Salomons T.V.
      • Davidson R.J.
      • Lutz A.
      Differential effects on pain intensity and unpleasantness of two meditation practices.
      but selectively modulated intensity in the other,
      • Grant J.A.
      • Rainville P.
      Pain sensitivity and analgesic effects of mindful states in Zen meditators: a cross-sectional study.
      which is interesting considering that the hypothesised effects focused on unpleasantness. The findings for the focused attention approach were similarly muddled. Focused attention had no effect in one study,
      • Perlman D.M.
      • Salomons T.V.
      • Davidson R.J.
      • Lutz A.
      Differential effects on pain intensity and unpleasantness of two meditation practices.
      and increased pain intensity in the other, but only in novice meditators.
      • Grant J.A.
      • Rainville P.
      Pain sensitivity and analgesic effects of mindful states in Zen meditators: a cross-sectional study.
      The two studies used focused attention in different ways: Perlman and colleagues
      • Perlman D.M.
      • Salomons T.V.
      • Davidson R.J.
      • Lutz A.
      Differential effects on pain intensity and unpleasantness of two meditation practices.
      used attention to a fixation cross, whereas Grant and Rainville
      • Grant J.A.
      • Rainville P.
      Pain sensitivity and analgesic effects of mindful states in Zen meditators: a cross-sectional study.
      used attention to the stimulus site.
      Full data were obtained for three studies.
      • Valentini E.
      • Betti V.
      • Hu L.
      colleagues
      Hypnotic modulation of pain perception and of brain activity triggered by nociceptive laser stimuli.
      • Kunz M.
      • Lautenbacher S.
      • LeBlanc N.
      • Rainville P.
      Are both the sensory and the affective dimensions of pain encoded in the face?.
      • Loggia M.L.
      • Mogil J.S.
      • Bushnell M.
      Experimentally induced mood changes preferentially affect pain unpleasantness.
      They used different manipulations, which prevented pooling. Their data are depicted in forest plots (see Fig. 2).
      Fig. 2
      Fig 2The effectiveness of selective modulation of the sensory and affective dimensions of pain.

      Discussion

      Despite apparent widespread support of the idea that the affective and sensory dimensions of pain can be selectively and intentionally modulated by different cognitive manipulations, our results reveal an evidence base that offers some support to both viewpoints, and is therefore far from clear-cut. Several studies showed selective downregulation of the affective dimension, but studies most compromised by potential bias showed the largest effects. Nine of 12 studies
      • Rainville P.
      • Duncan G.
      • Price D.
      • Carrier B.
      • Bushnell M.C.
      Pain affect encoded in human anterior cingulate but not somatosensory cortex.
      • Rainville P.
      • Carrier B.
      • Hofbauer R.K.
      • Bushnell M.C.
      • Duncan G.H.
      Dissociation of sensory and affective dimensions of pain using hypnotic modulation.
      • Hofbauer R.
      • Rainville P.
      • Duncan G.
      • Bushnell M.C.
      Cortical representation of the sensory dimension of pain.
      • Valentini E.
      • Betti V.
      • Hu L.
      colleagues
      Hypnotic modulation of pain perception and of brain activity triggered by nociceptive laser stimuli.
      • Villemure C.
      • Slotnick B.M.
      • Bushnell M.
      Effects of odors on pain perception: deciphering the roles of emotion and attention.
      • Kenntner-Mabiala R.
      • Andreatta M.
      • Wieser M.J.
      • Muhlberger A.
      • Pauli P.
      Distinct effects of attention and affect on pain perception and somatosensory evoked potentials.
      • Loggia M.L.
      • Mogil J.S.
      • Bushnell M.
      Experimentally induced mood changes preferentially affect pain unpleasantness.
      • Perlman D.M.
      • Salomons T.V.
      • Davidson R.J.
      • Lutz A.
      Differential effects on pain intensity and unpleasantness of two meditation practices.
      • Grant J.A.
      • Rainville P.
      Pain sensitivity and analgesic effects of mindful states in Zen meditators: a cross-sectional study.
      could not or did not selectively modulate the sensory dimension and the two studies that reported selective modulation of both dimensions, both using suggestion with or without hypnosis, had a very high risk of bias.
      • Dahlgren L.A.
      • Kurtz R.M.
      • Strube M.J.
      • Malone M.D.
      Differential effects of hypnotic suggestion on multiple dimensions of pain.
      • Kunz M.
      • Lautenbacher S.
      • LeBlanc N.
      • Rainville P.
      Are both the sensory and the affective dimensions of pain encoded in the face?.
      We conclude that the current evidence suggests that the sensory dimension of pain cannot be selectively modulated using cognitive manipulation, but the affective dimension might be.
      Which cognitive manipulation appears most likely to selectively modulate the affective dimension of pain? Of the four cognitive manipulations identified, the five studies that used hypnotic induction with suggestion demonstrated the most consistent effects.
      • Rainville P.
      • Duncan G.
      • Price D.
      • Carrier B.
      • Bushnell M.C.
      Pain affect encoded in human anterior cingulate but not somatosensory cortex.
      • Rainville P.
      • Carrier B.
      • Hofbauer R.K.
      • Bushnell M.C.
      • Duncan G.H.
      Dissociation of sensory and affective dimensions of pain using hypnotic modulation.
      • Hofbauer R.
      • Rainville P.
      • Duncan G.
      • Bushnell M.C.
      Cortical representation of the sensory dimension of pain.
      • Dahlgren L.A.
      • Kurtz R.M.
      • Strube M.J.
      • Malone M.D.
      Differential effects of hypnotic suggestion on multiple dimensions of pain.
      • Valentini E.
      • Betti V.
      • Hu L.
      colleagues
      Hypnotic modulation of pain perception and of brain activity triggered by nociceptive laser stimuli.
      Most of the studies involved the suggestion to decrease or increase pain unpleasantness. The scripts they used, however, did not necessarily mention unpleasantness. That is, scripts used words such as ‘agreeable’ or ‘comfortable’ or ‘restful’ when aiming to decrease unpleasantness, and words such as ‘uncomfortable’ when aiming to increase unpleasantness, but did not directly refer to pleasantness or unpleasantness specifically.
      • Rainville P.
      • Carrier B.
      • Hofbauer R.K.
      • Bushnell M.C.
      • Duncan G.H.
      Dissociation of sensory and affective dimensions of pain using hypnotic modulation.
      Similarly, one study used a suggestion of relaxation intended to decrease pain unpleasantness that was adapted from the Stanford Hypnotic Susceptibility Scale form C (SHSS).
      • Rainville P.
      • Duncan G.
      • Price D.
      • Carrier B.
      • Bushnell M.C.
      Pain affect encoded in human anterior cingulate but not somatosensory cortex.
      • Weitzenhoffer A.M.
      • Hilgard E.R.
      Stanford hypnotic susceptibility scale, form C.
      That three studies demonstrated that hypnosis without suggestion was ineffective, strongly implies that it was the suggestion itself that led to selective modulation of the affective dimension.
      • Rainville P.
      • Duncan G.
      • Price D.
      • Carrier B.
      • Bushnell M.C.
      Pain affect encoded in human anterior cingulate but not somatosensory cortex.
      • Rainville P.
      • Carrier B.
      • Hofbauer R.K.
      • Bushnell M.C.
      • Duncan G.H.
      Dissociation of sensory and affective dimensions of pain using hypnotic modulation.
      • Hofbauer R.
      • Rainville P.
      • Duncan G.
      • Bushnell M.C.
      Cortical representation of the sensory dimension of pain.
      This might appear concerning because it raises the possibility that the effect is simply one of reporting bias. However, two aspects of the literature suggest otherwise. First, the same suggestions were ineffective for the sensory dimension—presumably reporter bias would be equally applicable regardless of dimension. Second, the only study that also investigated neurophysiological markers demonstrated a biologically plausible effect on cortical activation.
      • Rainville P.
      • Duncan G.
      • Price D.
      • Carrier B.
      • Bushnell M.C.
      Pain affect encoded in human anterior cingulate but not somatosensory cortex.
      During the two control conditions called ‘wake control’ and ‘hypnotic control’, Rainville and colleagues
      • Rainville P.
      • Duncan G.
      • Price D.
      • Carrier B.
      • Bushnell M.C.
      Pain affect encoded in human anterior cingulate but not somatosensory cortex.
      demonstrated that no modulatory effect was observed in the S1, S2, the insular cortex, and the ACC. It was only hypnotic induction with suggestion that altered cortical activation. Therefore, it was hypnotic induction with specific suggestions about the affective dimension that selectively modulated the pain unpleasantness ratings and caused an alteration in the ACC activation. Similarly, it was hypnotic induction with specific suggestions about the sensory dimension that caused an alteration in the S1 activation; however, this did not translate to a selective modulation of pain intensity ratings. Although it clarifies that the effect is not merely a reflection of a participant's being under hypnosis, it is also potentially concerning because it suggests a differential effect of the manipulation on brain activity, but not on brain activity associated with production of pain.
      If we are to accept that suggestion can selectively modulate the affective dimension of pain, there are important caveats concerning generalisation and clinical utility. All five hypnosis studies recruited highly hypnotisable participants, but only 10–20% of the population is highly susceptible to hypnosis.
      • Rainville P.
      • Duncan G.
      • Price D.
      • Carrier B.
      • Bushnell M.C.
      Pain affect encoded in human anterior cingulate but not somatosensory cortex.
      • Rainville P.
      • Carrier B.
      • Hofbauer R.K.
      • Bushnell M.C.
      • Duncan G.H.
      Dissociation of sensory and affective dimensions of pain using hypnotic modulation.
      • Hofbauer R.
      • Rainville P.
      • Duncan G.
      • Bushnell M.C.
      Cortical representation of the sensory dimension of pain.
      • Dahlgren L.A.
      • Kurtz R.M.
      • Strube M.J.
      • Malone M.D.
      Differential effects of hypnotic suggestion on multiple dimensions of pain.
      • Valentini E.
      • Betti V.
      • Hu L.
      colleagues
      Hypnotic modulation of pain perception and of brain activity triggered by nociceptive laser stimuli.
      That the one study that included participants with low susceptibility to hypnosis had clearly lower modulatory effects leaves question marks over the potential utility of using suggestion to change pain unpleasantness.
      • Valentini E.
      • Betti V.
      • Hu L.
      colleagues
      Hypnotic modulation of pain perception and of brain activity triggered by nociceptive laser stimuli.
      Four studies demonstrated that selectively modulating the affective dimension of pain by using exteroceptive stimuli to change the valence of a test stimulus, were small effects—4.4 units or 3 units on a 100-unit scale.
      • Villemure C.
      • Slotnick B.M.
      • Bushnell M.
      Effects of odors on pain perception: deciphering the roles of emotion and attention.
      • Kenntner-Mabiala R.
      • Weyers P.
      • Pauli P.
      Independent effects of emotion and attention on sensory and affective pain perception.
      • Kenntner-Mabiala R.
      • Andreatta M.
      • Wieser M.J.
      • Muhlberger A.
      • Pauli P.
      Distinct effects of attention and affect on pain perception and somatosensory evoked potentials.
      • Loggia M.L.
      • Mogil J.S.
      • Bushnell M.
      Experimentally induced mood changes preferentially affect pain unpleasantness.
      Clearly, regardless of the mechanism of induction, the magnitude of effect is well short of that which might be considered clinically meaningful and, indeed, that which is measurable at an individual level.
      • Hawker G.A.
      • Mian S.
      • Kendzerska T.
      • French M.
      Measures of adult pain: visual analog scale for pain (VAS pain), numeric rating scale for pain (NRS pain), McGill pain Questionnaire (MPQ), short-form McGill pain Questionnaire (SF-MPQ), chronic pain grade scale (CPGS), short form-36 bodily pain scale (SF-36 BPS), and measure of intermittent and constant osteoarthritis pain (ICOAP).
      Why might the affective dimension be more modifiable than the sensory dimension? Relevant here might be data that show that most people conceptualise pain as a marker of tissue damage, which it has now been clearly shown not to be (see Moseley and Butler
      • Moseley G.L.
      • Butler D.
      Explain pain supercharged.
      for a comprehensive review of experimental and clinical studies).
      • Catley M.J.
      • O'Connell N.E.
      • Moseley G.L.
      How good is the Neurophysiology of Pain Questionnaire? A Rasch analysis of psychometric properties.
      • Moseley G.L.
      A pain neuromatrix approach to patients with chronic pain.
      We suspect that the participants in these studies would conceptualise their pain as ‘coming from the tissues’ rather than resulting from a highly complex evaluative process and a ‘best-guess output’ of the brain that reflects the predicted merit of taking protective action.
      • Moseley G.L.
      Evidence for a direct relationship between cognitive and physical change during an education intervention in people with chronic low back pain.
      If our suspicion is correct, it is not unreasonable to suggest that participants interpret the sensory dimension of pain as pain itself, which would render any cognitive attempt to reduce it seemingly pointless.
      • Tabor A.
      • Thacker M.A.
      • Moseley G.L.
      • colleagues
      Pain: a statistical account.
      • Tabor A.
      • O'Daly O.
      • Gregory R.W.
      • et al.
      Perceptual inference in chronic pain: an investigation into the economy of action hypothesis.
      Consistent with this idea is the clinical approach of mindfulness, in which the sufferer learns skills of acknowledging the pain by curbing a behavioural response to it, implying the immutable characteristics of pain's sensory but not affective dimension.
      • Rosenzweig S.
      • Greeson J.M.
      • Reibel D.K.
      • Green J.S.
      • Jasser S.A.
      • Beasley D.
      Mindfulness-based stress reduction for chronic pain conditions: variation in treatment outcomes and role of home meditation practice.
      A review of the meditation literature proposed mechanisms by which mindfulness or meditation may alter pain, focusing on its affective dimension, but compelling empirical data remain lacking.
      • Grant J.A.
      Meditative analgesia: the current state of the field.
      It is difficult to exclude demand effects as contributing mechanisms to the successful manipulations.
      • Turk D.C.
      • Melzack R.
      The measurement of pain and the assessment of people experiencing pain.
      Four of the five studies used a hypnotic suggestion that asked participants to either increase or decrease ‘pain intensity’, but none were successful. The fifth hypnosis study used a hypnotic suggestion of ‘analgesia’ to decrease pain intensity, and successfully achieved a selective modulation of sensory intensity ratings.
      • Dahlgren L.A.
      • Kurtz R.M.
      • Strube M.J.
      • Malone M.D.
      Differential effects of hypnotic suggestion on multiple dimensions of pain.
      It is plausible that the idea of analgesia was critical to this effect. The term ‘analgesia’ is usually used to describe an effect of medication, an agent that participants may understand to be capable of modulating sensory signalling.
      • Bingel U.
      • Wanigasekera V.
      • Wiech K.
      • et al.
      The effect of treatment expectation on drug efficacy: imaging the analgesic benefit of the opioid remifentanil.
      As such, the term ‘analgesia’ might possess conceptual validity that ‘reducing pain intensity’ does not.
      • Campbell P.
      • Bishop A.
      • Dunn K.M.
      • Main C.J.
      • Thomas E.
      • Foster N.E.
      Conceptual overlap of psychological constructs in low back pain.
      Certainly, expectation of pain relief modulates pain relief. For example, positive expectations about treatment seem to enhance the analgesic effect of opioid derived remifentanil, but negative expectations about treatment completely abolished the analgesic effect of remifentanil.
      • Bingel U.
      • Wanigasekera V.
      • Wiech K.
      • et al.
      The effect of treatment expectation on drug efficacy: imaging the analgesic benefit of the opioid remifentanil.
      Therefore, assessing conceptual understanding, expectation and self-efficacy in future studies of this topic would help with clarity.
      Despite our comprehensive and rigorous systematic review, the idea that pain comprises two separable dimensions is likely to remain somewhat controversial.
      • Chapman R.
      • Donaldson G.W.
      • Nakamura Y.
      • Jacobson R.C.
      • Bradshaw D.H.
      • Gavrin J.
      A psychophysiological causal model of pain report validity.
      Alternative views advocate for an understanding of pain as a unitary experience that involves different sensations, emotions, and cognitive processes that cannot be teased apart.
      • Price D.
      Psychological and neural mechanisms of the affective dimension of pain.
      • Chapman R.
      • Gavrin J.
      Suffering: the contributions of persistent pain.
      • Moseley G.L.
      Reconceptualising pain according to modern pain science.
      This view is supported by the apparent inability of untrained participants to separate pain into different dimensions.
      • Chapman R.
      • Nakamura Y.
      • Donaldson G.W.
      • et al.
      Sensory and affective dimensions of phasic pain are indistinguishable in the self-report and psychophysiology of normal laboratory subjects.
      • Fernandez E.
      • Turk D.C.
      Demand characteristics underlying differential ratings of sensory versus affective components of pain.
      • Chapman R.
      Limbic processes and the affective dimension of pain.
      Those studies that did not train participants to distinguish between the two dimensions found no difference between participants' ratings of the sensory and affective dimensions. Moreover, Fernandez and Turk
      • Fernandez E.
      • Turk D.C.
      Demand characteristics underlying differential ratings of sensory versus affective components of pain.
      showed that when participants rated each dimension on a separate week they failed to rate them differently, but when they were instructed to rate the two dimensions concurrently, they indeed provided distinct ratings. Such observations underpin the view that prising apart two dimensions from a unitary experience is, at best, pointless and, at worst, fallacious.
      • Fernandez E.
      • Turk D.C.
      Demand characteristics underlying differential ratings of sensory versus affective components of pain.
      A further and often overlooked point concerns the differences between experimental and clinical pain: experimental participants know that their pain will be short-lived, that they can withdraw at any time, and that there is very little or (most likely) no risk of injury.
      • Price D.
      • Harkins S.W.
      • Baker C.
      Sensory-affective relationships among different types of clinical and experimental pain.
      In contrast, chronic pain already has long-lasting pain, which they usually attribute to unresolved tissue damage.
      • Price D.
      • Harkins S.W.
      • Rafii A.
      • Price C.
      A simultaneous comparison of fentanyl's analgesic effects on experimental and clinical pain.
      Given these differences, the unpleasantness of pain in experimental settings may be less compelling, or perhaps more modifiable, because of this reduced biological need to motivate protective behaviour.
      • Moseley G.L.
      • Butler D.
      Explain pain supercharged.
      Moreover, participants in experimental pain studies arguably represent a subgroup of the general population—those who willingly volunteer for pain experiments. It is highly plausible that characteristics that render them willing to volunteer for pain experiments modulate their experiences and affect the mechanisms by which, and the extent to which, cognitive manipulations might modulate their pain.
      • Knudsen L.
      • Petersen G.L.
      • Nørskov K.N.
      • et al.
      Review of neuroimaging studies related to pain modulation.

       Future directions and limitations

      Several suggestions can be made for future work on the basis of this review. First, experimental studies need to adopt rigorous methodologies so as to avoid demand effects. Second, the risk of bias assessment identified the need to remove ceiling effects and carefully word the verbal anchors in self-report scales so as to avoid ambiguity and to limit response bias. Third, both participants and researchers should be blinded to condition and participants should be naïve to the experimental hypotheses (remarkably, such issues are both commonly emphasised and commonly neglected).
      • Park J.
      • Bang H.
      • Cañette I.
      Blinding in clinical trials, time to do it better.
      Fourth, raw data should be retained for longer periods of time to make pooling of data feasible for meta-analyses. This issue led to the main limitation of the current work—we were able to obtain raw data for only three of the 12 studies. Other limitations were as follows: the methodological challenges of the constituent studies and the possibility that our a priori selection criteria may have caused us to miss studies that inadvertently invoked selective modulation of separate dimensions of pain. However, the approach used by this systematic review was based on well-endorsed recommendations. A final consideration is the need to enhance reproducibility, for example full transparency in protocols, data analysis plans, and reporting.
      • Lee H.
      • Lamb S.E.
      • Bagg M.K.
      • Toomey E.
      • Cashin A.G.
      • Mosely G.L.
      Reproducible and replicable pain research: a critical review.

      Conclusion

      In contrast to popular opinion, evidence that the dimensions of pain can be selectively modulated using cognitive manipulations is weak. The most parsimonious conclusion seems to be that the sensory component cannot be selectively modulated, but the affective component might be, although significant threats to validity of the primary studies, and the risk of demand effects, warrant only tentative endorsement. If an effect does exist, it is likely to be very small. Although investigations of human pain have long considered these two dimensions of pain to be separable and differentially modifiable, the evidence suggests the alternative view, one that is usually held by people actually in pain—that pain is a unitary unpleasant and sensory experience. Several fundamental questions, with significant implications for the field, remain unanswered.

      Authors' contributions

      Study design: KT, VJM.
      Concept design: GLM.
      Data collection and analysis: KT, VJM.
      Drafting of the first version of the paper: KT.
      Editing of the paper: VJM, SJ, GLM.
      All authors approved the final version of the manuscript.

      Acknowledgements

      The authors acknowledge Karolína Hlávková, Nikolay Kadaryia, Johana Vankava, and Alexandra Sorvina for translating the non-English articles identified for full-text screening.

      Appendix A. Supplementary data

      The following are the Supplementary data to this article:

      Declarations of interest

      GLM receives payments for lectures and courses on pain and rehabilitation and he receives royalties for books on pain and rehabilitation. GLM and VM receive speaker fees for lectures on pain and rehabilitation. All the other authors declare no conflicts of interest.

      Funding

      NHMRC Principal Research Fellowship (# 1061279 ; to GLM). NHMRC Project grant (# 1047317 ; to GLM). Pfizer, Kaiser Permanente, Neuro Orthopaedic Institute, Workers' Compensation Boards in Australia and North America, Arsenal FC, Port Adelaide FC (to GLM). Oppenheimer Memorial Trust, South African National Research Foundation Innovation Postdoctoral Fellowship (to VJM). Australian Government Research Training Program (to KT).

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