Multidisciplinary Pain Management: A Tale of Two Outcomes.

Economic implications of pain management. By Loeser JD. Acta Anaesthesiol Scand 1999; 43:957-95. Reprinted with permission. Multidisciplinary pain management was an invention of John J. Bonica, M.D. He started the Multidisciplinary Pain Clinic at the University of Washington in 1960. This clinical service evolved over the years, and when John Loeser, M.D., became its director in 1982, he collaborated with Bill Fordyce, Ph.D., to create what was known as "the structured program." The program has served as the model for pain treatment programs throughout the world, many of which have fared better than that at the University of Washington. The migration of Stephen Butler, M.D., to Uppsala, Sweden, in 2000 has given us the opportunity to contrast multidisciplinary pain management in the Nordic countries with that in the United States.

Pain "chronification": what is the problem with this model?

OBJECTIVES: There appears to be an unwarranted focus on all chronic pain being a "chronification" of acute pain. Despite a plethora of studies on mechanisms to prevent this "chronification" following surgery, the positive effects have been minimal. An alternate model to explain chronic pain is presented. METHODS: Research in PUBMED and accessing data from the HUNTpain examination study. RESULTS: Data from the HUNT pain examination study reveal that less than 25% of individuals with chronic pain in a general population can relate the onset to an acute event. Another theory explaining the origin of chronic pain is that of priming and the accumulation of events that can be predictors along a continuum before chronic pain is apparent. This theory is presented to refocus for better prevention and treatment of chronic pain. CONCLUSIONS: "Chronification" cannot explain all cases of chronic/persistent pain. The plastic changes in the pain processing system can be seen as a continuum where at some point where an acute pain event is only one of several possible tipping points on this continuum that changes potential pain to perceived pain.

Social media 'addiction': The absence of an attentional bias to social media stimuli.

BACKGROUND AND AIMS: Social media use has become a ubiquitous part of society, with 3.8 billion users worldwide. While research has shown that there are positive aspects to social media engagement (e.g. feelings of social connectedness and wellbeing), much of the focus has been on the negative mental health outcomes which are associated with excessive use (e.g. higher levels of depression/anxiety). While the evidence to support such negative associations is mixed, there is a growing debate within the literature as to whether excessive levels of social media use should become a clinically defined addictive behaviour. METHODS: Here we assess whether one hallmark of addiction, the priority processing of addiction related stimuli known as an 'attentional bias', is evident in a group of social media users (N = 100). Using mock iPhone displays, we test whether social media stimuli preferentially capture users' attention and whether the level of bias can be predicted by platform use (self-report, objective smartphone usage data), and whether it is associated with scores on established measures of social media engagement (SMES) and social media 'addiction' severity scales (BSNAS, SMAQ). RESULTS: Our findings do not provide support for a social media specific attentional bias. While there was a large range of individual differences in our measures of use, engagement, and 'addictive' severity, these were not predictive of, or associated with, individual differences in the magnitude of attentional capture by social media stimuli. CONCLUSIONS: More research is required before social media use can be definitively placed within an addiction framework.

Memory-guided saccade processing in visual form agnosia (patient DF).

According to Milner and Goodale's model (The visual brain in action, Oxford University Press, Oxford, 2006) areas in the ventral visual stream mediate visual perception and oV-line actions, whilst regions in the dorsal visual stream mediate the on-line visual control of action. Strong evidence for this model comes from a patient (DF), who suffers from visual form agnosia after bilateral damage to the ventro-lateral occipital region, sparing V1. It has been reported that she is normal in immediate reaching and grasping, yet severely impaired when asked to perform delayed actions. Here we investigated whether this dissociation would extend to saccade execution. Neurophysiological studies and TMS work in humans have shown that the posterior parietal cortex (PPC), on the right in particular (supposedly spared in DF), is involved in the control of memory-guided saccades. Surprisingly though, we found that, just as reported for reaching and grasping, DF's saccadic accuracy was much reduced in the memory compared to the stimulus-guided condition. These data support the idea of a tight coupling of eye and hand movements and further suggest that dorsal stream structures may not be sufficient to drive memory-guided saccadic performance.

Modelling contralesional movement slowing after unilateral brain damage.

Effective interaction with the world requires the brain to signal behaviourally relevant events and organise an appropriate and timely motor response to such events. Unilateral brain lesion typically results in a reduction and slowing of motor behaviour directed to contralesional space. Accumulator models of choice and reaction time can distinguish between two possible functional causes of this deficit: slowed extraction of evidence in favour of a motor response or an increase in the required amount of evidence for response generation. Three patients with unilateral damage to the right hemisphere were tested on a visually guided saccade task. All three patients showed a dramatic increase in the latency of their responses to targets in the contralesional visual field. We fit their saccade latency distributions with a number of competing accumulator models that embody the alternative functional causes of this deficit. The latency difference between the two hemifields was best accounted for as an increase in the amount of evidence required for a contralesional response.

Revised chronic widespread pain criteria: development from and integration with fibromyalgia criteria.

Background and aims Persons with chronic widespread pain (CWP) have poor medical outcomes and increased mortality. But there are no universally accepted criteria for CWP or of methods to assess it. The most common criteria come from the 1990 American College of Rheumatology (ACR) fibromyalgia (FM) criteria, but that method (WP1990) can identify CWP with as few as three pain sites, and in subjects with wide differences in illness severity. Recently, to correct WP1990 deficiencies, the 2016 fibromyalgia criteria provided a modified CWP definition (WP2016) by dividing the body into five regions of three pain sites each and requiring a minimum of four regions of pain. Although solving the geographic problem of pain distribution, the problem of just how many pain sites (pain diffuseness) are required remained a problem, as WP2016 required as few as four painful sites. To better characterize CWP, we compared four CWP definitions with respect to symmetry, extent of pain sites and association with clinical severity variables. Methods We characterized pain in 40,960 subjects, including pain at 19 individual sites and five pain regions, and calculated the widespread pain index (WPI) and polysymptomatic distress scales (PDS) from epidemiology, primary care and rheumatology databases. We developed and evaluated a new definition for CWP, (WP2019), defined as pain in four or five regions and a pain site score of at least seven of 15 sites. We also tested a definition based on the number of painful sites (WPI ≥ 7). Results In rheumatology patients, WP1990 and WPI ≥ 7 classified patients with <4 regions as WSP. CWP was noted in 51.3% by WP1990, 41.7% by WP2016, 37.6% of WPI ≥ 7 and 33.9% by WP2019. 2016 FM criteria was satisfied in WP1990 (51.1%), WP2016 (63.3%), WPI ≥ 7 (69.0%) and WP2019 (76.6%). WP2019 positive patients had more severe clinical symptoms compared with WP1990, WP2016 and WPI ≥ 7, and similar to but less than FM 2016 positive patients. In stepwise fashion, scores for functional disability, visual analog scale fatigue and pain, WPI, polysymptomatic distress score and Patient Health Questionnaire 15 (PHQ-15) worsened from WP1990 through WP2016, WPI ≥ 7 and WP2019. Conclusions WP2019 combines the high WPI scores of WPI ≥ 7 and the symmetry of WP2016, and is associated with the most abnormal clinical scores. The WP1990 does not appear to be an effective measure. We suggest that CWP can be better defined by combining 4-region pain and a total pain site score ≥7 (WP2019). This definition provides a simple, unambiguous measure that is suitable for clinical and research use as a standalone diagnosis that is integrated with fibromyalgia definitions. Implications Definitions of CWP in research and clinic care are arbitrary and have varied, and different definitions of CWP identify different sets of patients, making a universal interpretation of CWP uncertain. In addition, CWP is a mandatory component of some fibromyalgia criteria. Our study provides quantitative data on the differences between CWP definitions and their criteria, allowing better understanding of research results and a guide to the use of CWP in clinical care.

Effects of aging and exposure duration on perceptual biases in chimeric face processing.

Experiments using chimeric faces, where the left and the right hand side of the face are different, have shown that observers tend to bias their responses toward the information on the left. Here we investigate the effects of aging as well as exposure duration on this leftward bias. Forty female and male blended as well as chimeric faces were presented to 24 young and 23 elderly adults in either sub-saccadic 100 msec, 300 msec or free view conditions. We found firstly that an increase in exposure duration resulted in an increase in the degree of leftward perceptual biases, irrespective of age, in line with hypotheses stressing the contribution of scanning to chimeric face processing. Secondly, fundamental differences in the perceptual biases between the groups were found in so far that the younger subjects demonstrated significant perceptual biases to chimeric face stimuli even at sub-saccadic exposure durations, whilst for older adults this was the case for the 300 msec and free view conditions only. This differential perceptual activity can be viewed in terms of either reduced right hemispheric function, or increased bilateral function as a possible consequence of elderly adults experiencing the task as more effortful.

Socio-cognitive load and social anxiety in an emotional anti-saccade task.

The anti-saccade task has been used to measure attentional control related to general anxiety but less so with social anxiety specifically. Previous research has not been conclusive in suggesting that social anxiety may lead to difficulties in inhibiting faces. It is possible that static face paradigms do not convey a sufficient social threat to elicit an inhibitory response in socially anxious individuals. The aim of the current study was twofold. We investigated the effect of social anxiety on performance in an anti-saccade task with neutral or emotional faces preceded either by a social stressor (Experiment 1), or valenced sentence primes designed to increase the social salience of the task (Experiment 2). Our results indicated that latencies were significantly longer for happy than angry faces. Additionally, and surprisingly, high anxious participants made more erroneous anti-saccades to neutral than angry and happy faces, whilst the low anxious groups exhibited a trend in the opposite direction. Results are consistent with a general approach-avoidance response for positive and threatening social information. However increased socio-cognitive load may alter attentional control with high anxious individuals avoiding emotional faces, but finding it more difficult to inhibit ambiguous faces. The effects of social sentence primes on attention appear to be subtle but suggest that the anti-saccade task will only elicit socially relevant responses where the paradigm is more ecologically valid.

Impaired peripheral reaching and on-line corrections in patient DF: Optic ataxia with visual form agnosia.

An influential model of vision suggests the presence of two visual streams within the brain: a dorsal occipito-parietal stream which mediates action and a ventral occipito-temporal stream which mediates perception. One of the cornerstones of this model is DF, a patient with visual form agnosia following bilateral ventral stream lesions. Despite her inability to identify and distinguish visual stimuli, DF can still use visual information to control her hand actions towards these stimuli. These observations have been widely interpreted as demonstrating a double dissociation from optic ataxia, a condition observed after bilateral dorsal stream damage in which patients are unable to act towards objects that they can recognize. In Experiment 1, we investigated how patient DF performed on the classical diagnostic task for optic ataxia, reaching in central and peripheral vision. We replicated recent findings that DF is remarkably inaccurate when reaching to peripheral targets, but not when reaching in free vision. In addition we present new evidence that her peripheral reaching errors follow the optic ataxia pattern increasing with target eccentricity and being biased towards fixation. In Experiments 2 and 3, for the first time we examined DF's on-line control of reaching using a double-step paradigm in fixation-controlled and free-vision versions of the task. DF was impaired when performing fast on-line corrections on all conditions tested, similarly to optic ataxia patients. Our findings question the long-standing assumption that DF's dorsal visual stream is functionally intact and that her on-line visuomotor control is spared. In contrast, in addition to visual form agnosia, DF also has visuomotor symptoms of optic ataxia which are most likely explained by bilateral damage to the superior parietal-occipital cortex (SPOC). We thus conclude that patient DF can no longer be considered as an appropriate single-case model for testing the neural basis of perception and action dissociations.

Perceptual biases in chimeric face processing: eye-movement patterns cannot explain it all.

Experiments using chimeric faces typically report a perceptual bias towards the viewers left. Here we show that this leftward bias can be elicited even when eye movement should be impossible. Although supporting previous studies arguing that eye movements are not necessary to generate the bias, the effect we found here was significantly reduced, compared to an earlier study which allowed eye movements. We suggest that the chimeric face bias is enhanced by eye movements.

The Effect of Self-Referential Expectation on Emotional Face Processing.

The role of self-relevance has been somewhat neglected in static face processing paradigms but may be important in understanding how emotional faces impact on attention, cognition and affect. The aim of the current study was to investigate the effect of self-relevant primes on processing emotional composite faces. Sentence primes created an expectation of the emotion of the face before sad, happy, neutral or composite face photos were viewed. Eye movements were recorded and subsequent responses measured the cognitive and affective impact of the emotion expressed. Results indicated that primes did not guide attention, but impacted on judgments of valence intensity and self-esteem ratings. Negative self-relevant primes led to the most negative self-esteem ratings, although the effect of the prime was qualified by salient facial features. Self-relevant expectations about the emotion of a face and subsequent attention to a face that is congruent with these expectations strengthened the affective impact of viewing the face.

Perceptual bias, more than age, impacts on eye movements during face processing.

Consistent with the right hemispheric dominance for face processing, a left perceptual bias (LPB) is typically demonstrated by younger adults viewing faces and a left eye movement bias has also been revealed. Hemispheric asymmetry is predicted to reduce with age and older adults have demonstrated a weaker LPB, particularly when viewing time is restricted. What is currently unclear is whether age also weakens the left eye movement bias. Additionally, a right perceptual bias (RPB) for facial judgments has less frequently been demonstrated, but whether this is accompanied by a right eye movement bias has not been investigated. To address these issues older and younger adults' eye movements and gender judgments of chimeric faces were recorded in two time conditions. Age did not significantly weaken the LPB or eye movement bias; both groups looked initially to the left side of the face and made more fixations when the gender judgment was based on the left side. A positive association was found between LPB and initial saccades in the freeview condition and with all eye movements (initial saccades, number and duration of fixations) when time was restricted. The accompanying eye movement bias revealed by LPB participants contrasted with RPB participants who demonstrated no eye movement bias in either time condition. Consequently, increased age is not clearly associated with weakened perceptual and eye movement biases. Instead an eye movement bias accompanies an LPB (particularly under restricted viewing time conditions) but not an RPB.

Does inversion abolish the left chimeric face processing advantage?

Experiments using chimeric stimuli have shown that the right hemisphere is more influential in processing facial information. Here, again, we found clear evidence that study participants used the information from the left side of the face to inform their gender decisions when chimeric male/female, female/male stimuli were presented. Most interestingly though, this effect was not only present for upright faces but also for inverted (flipped) faces (although the effect was significantly reduced). We propose that the chimeric bias effects found here argue against the idea that inversion destroys the right hemisphere superiority for faces. If this was indeed the case, flipping the chimeric faces should have resulted in a loss of the left face bias. This was not the case.

Effects of doxepin on perception of laboratory-induced pain in man.

Beneficial effects have been observed in University of Washington Pain Clinic patients treated with tricyclic antidepressants, but such effects occur much earlier than predicted mood elevation. A laboratory investigation of pain perception was employed to test the hypothesis that doxepin, a tricyclic antidepressant, has analgesic properties. Healthy, normal volunteers were tested over a 4-week period during which they repeatedly performed Sensory Decision Theory tasks while undergoing painful dental stimulation. Doxepin and a placebo were administered after baseline measurement for 4 weeks under double blind conditions. No significant changes due to drug administration were observed in detection threshold or sensory sensitivity indices, but response bias against reporting the stimuli as painful changed dramatically after subjects began ingesting capsules. This effect was evident in both drug and placebo groups, and it was maintained across repeated weeks of testing. These observations suggest that the instructions given patients when the drug is administered have a profound effect on pain report.

Reduction of arthritis and pain behaviour following chronic administration of amitriptyline or imipramine in rats with adjuvant-induced arthritis.

Tricyclic antidepressants (TCAs) are used extensively to treat chronic pain in man without an adequate explanation for their activity. The purpose of the present study was to investigate this problem by testing the effect of chronic TCAs in an animal pain model: the arthritic rat. Sprague-Dawley rats with adjuvant-induced arthritis were injected daily for 4 weeks with amitriptyline (10 mg/kg) or imipramine (10 mg/kg) or saline, beginning 21 days after the induction of arthritis. Baseline evaluations were made prior to the injection series and at 4 weeks, 24 h after the last injection. Both TCAs significantly reduced 'scratching' and increased 'exploring' behaviour, without changing the response to graded foot pressure. In addition clinical signs of arthritis (ankle circumference, swelling, conjunctivitis, balanitis ...) were significantly reduced, while mobility was increased. This study shows that both amitriptyline and imipramine decrease pain behaviour and arthritis in this chronic pain model. Possible 'antiinflammatory' effects of TCAs and their eventual 'analgesic' effect will be discussed.

A limited arthritic model for chronic pain studies in the rat.

Freund's adjuvant induced polyarthritis in rats has been used extensively to study pain processes of long duration. There are limitations of this model for chronic studies of pain/arthritis since the severe systemic changes provoke ethical concerns and also affect behaviour, physiology and biochemistry. Attempts to limit adjuvant-induced arthritis by plantar injection of the inoculum have been made. In this model, however, the process evolved to produce widespread polyarthritis if followed for the 6-plus-weeks necessary for chronic studies. Therefore, although it offers the researcher a reliable limited model of inflammation and nociception at the outset, for longer studies it may have all the disadvantages of the polyarthritic rat. The purpose of the present study was to produce a limited arthritic process in rats, stable over 6 weeks and suitable for behavioural and neurochemical studies of various chronic pain treatment methods. Injection (0.05 ml) of complete adjuvant containing 300 micrograms Mycobacterium butyricum in the tibio-tarsal joint produces a predictable monoarthritis, stable clinically and behaviourly from weeks 2 through 6 post injection. As revealed by clinical observations and X-ray examinations, the arthritis produced was limited anatomically, pronounced, prolonged and stable. A marked increase in sensitivity to paw pressure was seen in the affected limb. Animals gained weight and remained active, indicating little systemic disturbance as opposed to polyarthritic rats. We propose this limited model of arthritis as a suitable alternative to the polyarthritic rat for prolonged studies.

Do acute or chronic tricyclic antidepressants modify morphine antinociception in arthritic rats?

In a chronic pain model, the arthritic rat, tricyclic antidepressants (TCAs) have been shown to clearly reduce behavioural signs of nociception. In the present work, using a test of acute nociception (vocalization threshold to graded foot pressure) in the same model, we evaluated the possible potentiation of morphine analgesia by 2 TCAs: amitriptyline (AMIT) and imipramine (IMIP). Using this test of acute nociception, we failed to demonstrate any analgesic effect of AMIT or IMIP given either acutely or chronically. We also failed to demonstrate any potentiation of morphine by these compounds. On the contrary, we found a significant decrease of morphine antinociception after acute AMIT administration and a tendency towards diminution with both TCAs given chronically. These results appear to temper enthusiasm for human application of this combination. They also indicate that careful further studies in a chronic pain model using behaviour evaluations are necessary before definite conclusions can be drawn concerning TCAs/opiate interaction.