Showing papers in "Pain in 1999"

Pain-related fear is more disabling than pain itself: evidence on the role of pain-related fear in chronic back pain disability.

Abstract: There is growing evidence for the idea that in back pain patients, pain-related fear (fear of pain/physical activity/(re)injury) may be more disabling than pain itself. A number of questionnaires have been developed to quantify pain-related fears, including the Fear-Avoidance Beliefs Questionnaire (FABQ), the Tampa Scale for Kinesiophobia (TSK), and the Pain Anxiety Symptoms Scale (PASS). A total of 104 patients, presenting to a rehabilitation center or a comprehensive pain clinic with chronic low back pain were studied in three independent studies aimed at (1) replicating that pain-related fear is more disabling than pain itself (2) investigating the association between pain-related fear and poor behavioral performance and (3) investigating whether pain-related fear measures are better predictors of disability and behavioral performance than measures of general negative affect or general negative pain beliefs (e.g. pain catastrophizing). All three studies showed similar results. Highest correlations were found among the pain-related fear measures and measures of self-reported disability and behavioral performance. Even when controlling for sociodemographics, multiple regression analyses revealed that the subscales of the FABQ and the TSK were superior in predicting self-reported disability and poor behavioral performance. The PASS appeared more strongly associated with pain catastrophizing and negative affect, and was less predictive of pain disability and behavioral performance. Implications for chronic back pain assessment, prevention and treatment are discussed.

Systematic review and meta-analysis of randomized controlled trials of cognitive behaviour therapy and behaviour therapy for chronic pain in adults, excluding headache

Abstract: A computer and a hand search of the literature recovered 33 papers from which 25 trials suitable for meta-analysis were identified. We compared the effectiveness of cognitive-behavioural treatments with the waiting list control and alternative treatment control conditions. There was a great diversity of measurements which we grouped into domains representing major facets of pain. Effect sizes, corrected for measurement unreliability, were estimated for each domain. When compared with the waiting list control conditions cognitive-behavioural treatments were associated with significant effect sizes on all domains of measurement (median effect size across domains=0.5). Comparison with alternative active treatments revealed that cognitive-behavioural treatments produced significantly greater changes for the domains of pain experience, cognitive coping and appraisal (positive coping measures), and reduced behavioural expression of pain. Differences on the following domains were not significant; mood/affect (depression and other, non-depression, measures), cognitive coping and appraisal (negative, e.g. catastrophization), and social role functioning. We conclude that active psychological treatments based on the principle of cognitive behavioural therapy are effective. We discuss the results with reference to the complexity and quality of the trials.

Efficacy of pharmacological treatments of neuropathic pain: an update and effect related to mechanism of drug action.

Abstract: Tricyclic antidepressants and carbamazepine have become the mainstay in the treatment of neuropathic pain. Within the last decade, controlled trials have shown that numerous other drugs relieve such pain. We identified all placebo-controlled trials and calculated numbers needed to treat (NNT) to obtain one patient with more than 50% pain relief in order to compare the efficacy with the current treatments, and to search for relations between mechanism of pain and drug action. In diabetic neuropathy, NNT was 1.4 in a study with optimal doses of the tricyclic antidepressant imipramine as compared to 2.4 in other studies on tricyclics. The NNT was 6.7 for selective serotonin reuptake inhibitors, 3.3 for carbamazepine, 10.0 for mexiletine, 3.7 for gabapentin, 1.9 for dextromethorphan, 3.4 for tramadol and levodopa and 5.9 for capsaicin. In postherpetic neuralgia, the NNT was 2.3 for tricyclics, 3.2 for gabapentin, 2.5 for oxycodone and 5.3 for capsaicin, whereas dextromethorphan was inactive. In peripheral nerve injury, NNT was 2.5 for tricyclics and 3.5 for capsaicin. In central pain, NNT was 2.5 for tricyclics and 3. 4 for carbamazepine, whereas selective serotonin reuptake inhibitors, mexiletine and dextromethorphan were inactive. There were no clear relations between mechanism of action of the drugs and the effect in distinct pain conditions or for single drug classes and different pain conditions. It is concluded that tricyclic antidepressants in optimal doses appear to be the most efficient treatment of neuropathic pain, but some of the other treatments may be important due to their better tolerability. Relations between drug and pain mechanisms may be elucidated by studies focusing on specific neuropathic pain phenomena such as pain paroxysms and touch-evoked pain.

Comparative reliability and validity of chronic pain intensity measures.

Abstract: Reliable and valid measures of pain are essential for conducting research on chronic pain. The purpose of this longitudinal study was to compare the reliability and validity of several measures of pain intensity. One hundred twenty-three patients with chronic pain were administered telephone interview versions of 0-10 scales of current, worst, least and average pain, immediately prior to beginning a multidisciplinary treatment program. The measures were administered again to these subjects 2 weeks (n=108), 1 month (n=106) and 2 months (n=105) after the end of treatment. The validity (defined as ability to detect changes in pain intensity over the course of treatment up to the 2-month follow-up assessment) and reliability (defined as stability over time in the 2 months after treatment) of these four measures and of composite combinations of these measures were examined. Contrary to prediction, the composite measures did not show a statistically significant superiority to the individual ratings in terms of their ability to detect change in pain intensity from pre-treatment to various points after treatment. The composite scores did, however, show greater stability than did the individual ratings after treatment. The practical conclusions of this study are; (1), individual 0-10 pain intensity ratings have sufficient psychometric strengths to be used in chronic pain research, especially research that involves group comparison designs with relatively large sample sizes, but, (2), composites of 0-10 ratings may be more useful when maximal reliability is necessary, (e.g. in studies with relatively small sample sizes, or in clinical settings where monitoring of changes in pain intensity in individuals is needed).

From the gate to the neuromatrix.

Abstract: The gate control theory's most important contribution to understanding pain was its emphasis on central neural mechanisms. The theory forced the medical and biological sciences to accept the brain as an active system that filters, selects and modulates inputs. The dorsal horns, too, were not merely passive transmission stations but sites at which dynamic activities (inhibition, excitation and modulation) occurred. The great challenge ahead of us is to understand brain function. I have therefore proposed that the brain possesses a neural network--the body-self neuromatrix--which integrates multiple inputs to produce the output pattern that evokes pain. The body-self neuromatrix comprises a widely distributed neural network that includes parallel somatosensory, limbic and thalamocortical components that subserve the sensory-discriminative. affective-motivational and evaluative-cognitive dimensions of pain experience. The synaptic architecture of the neuromatrix is determined by genetic and sensory influences. The 'neurosignature' output of the neuromatrix--patterns of nerve impulses of varying temporal and spatial dimensions--is produced by neural programs genetically build into the neuromatrix and determines the particular qualities and other properties of the pain experience and behavior. Multiple inputs that act on the neuromatrix programs and contribute to the output neurosignature include. (1) sensory inputs (cutaneous, visceral and other somatic receptors); (2) visual and other sensory inputs that influence the cognitive interpretation of the situation; (3) phasic and tonic cognitive and emotional inputs from other areas of the brain; (4) intrinsic neural inhibitory modulation inherent in all brain function; (5) the activity of the body's stress-regulation systems, including cytokines as well as the endocrine, autonomic, immune and opioid systems. We have traveled a long way from the psychophysical concept that seeks a simple one-to-one relationship between injury and pain. We now have a theoretical framework in which a genetically determined template for the body-self is modulated by the powerful stress system and the cognitive functions of the brain, in addition to the traditional sensory inputs.

The cortical representation of pain.

Abstract: Anatomical and physiological studies in animals, as well as functional imaging studies in humans have shown that multiple cortical areas are activated by painful stimuli. The view that pain is perceived only as a result of thalamic processing has, therefore, been abandoned, and has been replaced by the question of what functions can be assigned to individual cortical areas. The following cortical areas have been shown to be involved in the processing of painful stimuli: primary somatosensory cortex, secondary somatosensory cortex and its vicinity in the parietal operculum, insula, anterior cingulate cortex and prefrontal cortex. These areas probably process different aspects of pain in parallel. Previous psychophysical research has emphasized the importance of separating pain experience into sensory-discriminative and affective-motivational components. The sensory-discriminative component of pain can be considered a sensory modality similar to vision or olfaction; it becomes more and more evident that it is subserved by its own apparatus up to the cortical level. The affective-motivational component is close to what may be considered 'suffering from pain'; it is clearly related to aspects of emotion, arousal and the programming of behaviour. This dichotomy, however, has turned out to be too simple to explain the functional significance of nociceptive cortical networks. Recent progress in imaging technology has, therefore, provided a new impetus to study the multiple dimensions of pain.

Breakthrough pain: characteristics and impact in patients with cancer pain

Abstract: Few surveys have been performed to define the characteristics and impact of breakthrough pain in the cancer population. In this cross-sectional survey of inpatients with cancer, patients responded to a structured interview (the Breakthrough Pain Questionnaire) designed to characterize breakthrough pain, and also completed measures of pain and mood (Memorial Pain Assessment Card (MPAC)), pain-related interference in function (Brief Pain Inventory (BPI)), depressed mood (Beck Depression Inventory (BDI)), and anxiety (Beck Anxiety Inventory (BAI)). Of 178 eligible patients, 164 (92.2%) met the criteria for controlled background pain. The median age was 50.6 years (range 26 to 77 years), 52% were men, and 80.6% were Caucasian. Tumor diagnoses were mixed, 75% had metastatic disease, 65% had pain caused directly by the neoplasm, and a majority had mixed nociceptive-neuropathic pain. The median Karnofsky Performance Status score was 60 (range 40 to 90). Eighty-four (51.2%) patients had experienced breakthrough pain during the previous day. The median number of episodes was six (range 1 to 60) and the median interval from onset to peak was 3 min (range 1 s to 30 min). Although almost two-thirds (61.7%) could identify precipitants (movement 20.4%; end-of-dose failure 13.2%), pain was unpredictable in a large majority (78.2%). Patients with breakthrough pain had more intense (P < 0.001) and more frequent (P < 0.01) background pain than patients without breakthrough pain. Breakthrough pain was also associated with greater pain-related functional impairment (difference in mean BPI. P < 0.001), worse mood (mood VAS, P < 0.05; BDI, P < 0.001), and more anxiety (BAI, P < 0.001). Multivariate analysis confirmed that breakthrough pain independently contributed to impaired functioning and psychological distress. These data confirm that cancer-related breakthrough pain is a prevalent and heterogeneous phenomenon. The presence of breakthrough pain is a marker of a generally more severe pain syndrome, and is associated with both pain-related functional impairment and psychological distress. The findings suggest the need for further studies of breakthrough pain and more effective therapeutic strategies.

Heritability of nociception I: responses of 11 inbred mouse strains on 12 measures of nociception.

Abstract: It is generally acknowledged that humans display highly variable sensitivity to pain, including variable responses to identical injuries or pathologies. The possible contribution of genetic factors has, however, been largely overlooked. An emerging rodent literature documents the importance of genotype in mediating basal nociceptive sensitivity, in establishing a predisposition to neuropathic pain following neural injury, and in determining sensitivity to pharmacological agents and endogenous antinociception. One clear finding from these studies is that the effect of genotype is at least partially specific to the nociceptive assay being considered. In this report we begin to systematically describe and characterize genetic variability of nociception in a mammalian species, Mus musculus. We tested 11 readily-available inbred mouse strains (129/J, A/J, AKR/J, BALB/cJ, C3H/HeJ, C57BL/6J, C58/J, CBA/J, DBA/2J, RIIIS/J and SM/J) using 12 common measures of nociception. These included assays for thermal nociception (hot plate, Hargreaves' test, tail withdrawal), mechanical nociception (von Frey filaments), chemical nociception (abdominal constriction, carrageenan, formalin), and neuropathic pain (autotomy, Chung model peripheral nerve injury). We demonstrate the existence of clear strain differences in each assay, with 1.2 to 54-fold ranges of sensitivity. All nociceptive assays display moderate-to-high heritability (h2 = 0.30-0.76) and mediation by a limited number of apparent genetic loci. Data comparing inbred strains have considerable utility as a tool for understanding the genetics of nociception, and a particular relevance to transgenic studies.

External validation of IASP diagnostic criteria for Complex Regional Pain Syndrome and proposed research diagnostic criteria

Abstract: Recent work in our research consortium has raised internal validity concerns regarding the current IASP criteria for Complex Regional Pain Syndrome (CRPS), suggesting problems with inadequate sensitivity and specificity. The current study explored the external validity of these IASP criteria for CRPS. A standardized evaluation of signs and symptoms of CRPS was conducted by study physicians in 117 patients meeting IASP criteria for CRPS, and 43 patients experiencing neuropathic pain with established non-CRPS etiology (e.g. diabetic neuropathy, post-herpetic neuralgia). Multiple discriminant function analyses were used to test the ability of the IASP diagnostic criteria and decision rules, as well as proposed research modifications of these criteria, to discriminate between CRPS patients and those experiencing non-CRPS neuropathic pain. Current IASP criteria and decision rules (e.g. signs or symptoms of edema, or color changes or sweating changes satisfy criterion 3) discriminated significantly between groups (P < 0.001). However, although sensitivity was quite high (0.98), specificity was poor (0.36), and a positive diagnosis of CRPS was likely to be correct in as few as 40% of cases. Empirically-based research modifications to the criteria, which are more comprehensive and require presence of signs and symptoms, were also tested. These modified criteria were also able to discriminate significantly, between the CRPS and non-CRPS groups (P < 0.001). A decision rule, requiring at least two sign categories and four symptom categories to be positive optimized diagnostic efficiency, with a diagnosis of CRPS likely to be accurate in up to 84% of cases, and a diagnosis of non-CRPS neuropathic pain likely to be accurate in up to 88% of cases. These results indicate that the current IASP criteria for CRPS have inadequate specificity and are likely to lead to overdiagnosis. Proposed modifications to these criteria substantially improve their external validity and merit further evaluation.

An international survey of cancer pain characteristics and syndromes

Abstract: The optimal assessment of cancer pain includes a detailed description of pain characteristics and classification by both syndrome and likely mechanisms. In the clinical setting, the interpretation of this information is aided by knowledge of the available clinical experiences on these aspects of the pain. Unfortunately, existing data are limited. There have been few large surveys of cancer pain characteristics and syndromes, and comparative data from patients in different parts of the world are entirely lacking. To better define the characteristics of cancer pain syndromes the Task Force on Cancer Pain of the International Association for the Study of Pain (IASP) conducted a prospective, cross-sectional, international, multicenter survey of pain specialists and their patients. From a total of 100 clinicians who described themselves as cancer pain practitioners in the IASP membership directory, 51 agreed to participate in the survey and a total of 58 provided data. These clinicians resided in 24 countries and evaluated a total of 1095 patients with severe cancer pain mostly requiring opioid medication, using a combination of patient-rated and observer-rated measures. The patient-rated scales comprised a pain intensity measure chosen from the brief pain inventory. The observer-rated information included demographic and tumor-related data, and responses on checklists of pain syndromes and pathophysiologies. Patients were heterogeneous in terms of demographics and tumor-related information. More than 76% had a Kamofsky performance status score or = 7 on a 10-point numeric scale. The factors that were univariately associated with higher pain intensity included the presence of breakthrough pain, somatic pain or neuropathic pain, age younger than 60 years, and lower performance status score. A multivariate model suggested that the presence of breakthrough pain, somatic pain, and lower performance status were the most important predictors of intense pain. Pains that were inferred by the treating clinician to be nociceptive and due to somatic injury occurred in 71.6% of the patients. Pains labeled nociceptive visceral were noted in 34.7% and pains inferred to have neuropathic mechanisms occurred in 39.7%. In a broad classification, the major pain syndromes comprised bone or joint lesions (41.7% of patients), visceral lesions (28.1%), soft tissue infiltration (28.3%), and peripheral nerve injuries (27.8%). Twenty-two types of pain syndromes were most prevalent. Large differences in the diagnosis of breakthrough pain by clinicians of different countries suggest that this phenomenon is either defined or recognized differently across countries. These data confirm, in segment of the cancer population experiencing severe pain, in different parts of the world, that cancer pain characteristics, syndromes and pathophysiologies are very heterogeneous. Predictors of worsening pain can be identified. The data provide a useful context for the interpretation of pain-related information acquired in both clinical and research settings. They suggest the need for future studies and the potential usefulness of a written checklist for cancer pain syndromes and pathophysiologies.

An analysis of factors that contribute to the magnitude of placebo analgesia in an experimental paradigm

Abstract: Placebo analgesia was produced by conditioning trials wherein heat induced experimental pain was surreptitiously reduced in order to test psychological factors of expectancy and desire for pain reduction as possible mediators of placebo analgesia. The magnitudes of placebo effects were assessed after these conditioning trials and during trials wherein stimulus intensities were reestablished to original baseline levels. In addition, analyses were made of the influence of these psychological factors on concurrently assessed pain and remembered pain intensities. Statistically reliable placebo effects on sensory and affective measures of pain were graded according to the extent of surreptitious lowering of stimulus strength during the manipulation trials, consistent with conditioning. However, all of these effects were strongly associated with expectancy but not desire for relief. These results show that although conditioning may be sufficient for placebo analgesia, it is likely to be mediated by expectancy. The results further demonstrated that placebo effects based on remembered pain were 3 to 4 times greater than those based on concurrently assessed placebo effects, primarily because baseline pain was remembered as being much more intense than it actually was. However, similar to concurrent placebo effects, remembered placebo effects were strongly associated with expected pain levels that occurred just after conditioning. Taken together, these results suggest that magnitudes of placebo effect are dependent on multiple factors, including conditioning, expectancy, and whether analgesia is assessed concurrently or retrospectively.

Use and efficacy of low-dose ketamine in the management of acute postoperative pain: a review of current techniques and outcomes.

Abstract: Ketamine hydrochloride is a well known general anesthetic and short acting analgesic in use for almost 3 decades. The role of the NMDA receptor in the processing of nociceptive input has led naturally to renewed clinical interest in N-methyl-D-aspartate (NMDA) receptor antagonists such as ketamine. This paper reviews the use and efficacy of low-dose ketamine in the management of acute postoperative pain. The literature was obtained from a computer search of the MEDLINE database from 1966 through December 1998. Studies were included for review if they were randomized, prospective, controlled, double-blind and reported pain scores. We evaluate the clinical literature and discuss the efficacy of low-dose ketamine in the management of acute postoperative pain when administered alone or in conjunction with other agents via the oral, intramuscular, subcutaneous, intravenous and intraspinal routes. Low-dose ketamine is defined as a bolus dose of less than 2 mg/g when given intramuscularly or less than 1 mg/kg when administered via the intravenous or epidural route. For continuous i.v. administration low-dose ketamine is defined as a rate of < or =20 microg/kg per min. We conclude that ketamine may provide clinicians with a tool to improve postoperative pain management and to reduce opioid related adverse effects. The evidence suggests that low-dose ketamine may play an important role in postoperative pain management when used as an adjunct to local anesthetics, opioids, or other analgesic agents. Further research is required in the following areas: (a) dose-finding studies for ketamine as an adjunct to opioids and local anesthetics (b) efficacy and optimal route of administration (c) the role of S(+)-ketamine; (d) the influence of ketamine on long-term outcome such as chronic pain (e) long-term physical and chemical stability of mixtures containing ketamine (f) spinal toxicity of ketamine and (g) effects of low-dose ketamine on cognitive and memory functioning after surgery.

Electrical stimulation of motor cortex for pain control: a combined PET-scan and electrophysiological study☆

Abstract: Although electrical stimulation of the precentral gyrus (MCS) is emerging as a promising technique for pain control, its mechanisms of action remain obscure, and its application largely empirical. Using positron emission tomography (PET) we studied regional changes in cerebral flood flow (rCBF) in 10 patients undergoing motor cortex stimulation for pain control, seven of whom also underwent somatosensory evoked potentials and nociceptive spinal reflex recordings. The most significant MCS-related increase in rCBF concerned the ventral-lateral thalamus, probably reflecting cortico-thalamic connections from motor areas. CBF increases were also observed in medial thalamus, anterior cingulate/orbitofrontal cortex, anterior insula and upper brainstem; conversely, no significant CBF changes appeared in motor areas beneath the stimulating electrode. Somatosensory evoked potentials from SI remained stable during MCS, and no rCBF changes were observed in somatosensory cortex during the procedure. Our results suggest that descending axons, rather than apical dendrites, are primarily activated by MCS, and highlight the thalamus as the key structure mediating functional MCS effects. A model of MCS action is proposed, whereby activation of thalamic nuclei directly connected with motor and premotor cortices would entail a cascade of synaptic events in pain-related structures receiving afferents from these nuclei, including the medial thalamus, anterior cingulate and upper brainstem. MCS could influence the affective-emotional component of chronic pain by way of cingulate/orbitofrontal activation, and lead to descending inhibition of pain impulses by activation of the brainstem, also suggested by attenuation of spinal flexion reflexes. In contrast, the hypothesis of somatosensory cortex activation by MCS could not be confirmed by our results.

A meta-analytic review of pain perception across the menstrual cycle.

Abstract: The purpose of this article is to review the sixteen published studies that examine associations between the perception of experimentally induced pain across menstrual cycle phases of healthy females. We also performed a meta-analysis to quantitatively analyze the data and attempt to draw conclusions. The results suggest that there are relatively consistent patterns in the sensitivity to painful stimulation. These patterns are similar across stimulus modality with the exception of electrical stimulation. The magnitude of the effect was approximately 0.40 across all stimulation. For pressure stimulation, cold pressor pain, thermal heat stimulation, and ischemic muscle pain, a clear pattern emerges with the follicular phase demonstrating higher thresholds than later phases. When the effect size was pooled across studies (excluding electrical) comparisons involving the follicular phase were small to moderate (periovulatory phase, dthr=0.34; luteal phase, dthr=0.37; premenstrual phase, dthr=0.48). The pattern of effects was similar for tolerance measures. Electrical stimulation was different than the other stimulus modalities, showing the highest thresholds for the luteal phase. When the effect size was pooled across studies for electrical stimulation, effect sizes were small to moderate (menstrual (dthr=−0.37), follicular dthr=−0.30) periovulatory dthr=−0.61), and premenstrual dthr=0.35) phases. This paper raises several important questions, which are yet to be answered. How much and in wha way does this menstrual cycle effect bias studies of female subjects participating in clinical trials? Furthermore, how should studies of clinical pain samples control for menstrual related differences in pain ratings and do they exist in clinical pain syndromes? What this paper does suggest is that the menstrual cycle effect on human pain perception is too large to ignore.

Dissociation of sensory and affective dimensions of pain using hypnotic modulation.

Abstract: Understanding the complex nature of pain perception requires the ability to separately analyze its psychological dimensions and their interaction, and relate them to specific variables and responses. The present study, therefore, attempted to selectively modulate the sensory and affective dimensions of pain, using a cognitive intervention, and to assess the possible relationship between these psychological dimensions of pain and changes in physiological responses to the noxious stimuli. In three experiments, normal subjects trained in hypnosis rated pain intensity and pain unpleasantness produced by a tonic heat-pain stimulus (1-min immersion of the hand in 45.0-47.5 degrees C water). Two experiments were designed to test hypnotic suggestions to decrease (Experiment one (Section 2.5.1)), or increase and decrease (Experiment two (Section 2.5.2)) pain affect. Suggestions in Experiment three (Section 2.5.3) were directed towards an increase or decrease in pain sensation. In Experiments one and two (Sections 2.5.1 and 2.5.2), the significant modulation in pain unpleasantness ratings was largely independent of variations in perceived pain intensity. Moreover, in Experiment two (Section 2.5.2), there was a significant correlation between the stimulus-evoked heart-rate increase and ratings of pain unpleasantness, but not of pain intensity, suggesting a direct functional interaction between pain affect and autonomic activation. In Experiment three (Section 2.5.3), suggestions to modulate the sensory aspect of pain produced significant modulation of pain intensity ratings, with secondary changes in pain unpleasantness ratings. Hypnotic susceptibility (Stanford Hypnotic Susceptibility Scale form A) was specifically correlated to pain unpleasantness modulation in Experiment two (Section 2.5.2) and to pain intensity modulation in Experiment three (Section 2.5.3), suggesting that this factor relates to the primary process toward which hypnotic suggestions are directed. The specific pain dimension on which hypnotic suggestions act depends on the content of the instructions and is not a characteristic of hypnosis itself. Results are consistent with a successive-stage model of pain perception (e.g. Wade JB, Dougherty LM, Archer CR, Price DD. Assessing the stages of pain processing: a multivariate analytical approach. Pain 1996;68:157-167) which provides a conceptual framework necessary to study the cerebral representation of pain perception.

Cost-of-illness of neck pain in The Netherlands in 1996.

Abstract: The prevalence of neck pain in the general population ranges from 10 to 15%. The complaints can result in substantial medical consumption, absenteeism from work and disability. In this study we investigated the costs of neck pain in the Netherlands in 1996 to assess the financial burden to society. The study was based on prevalence data. Data sources included national registries, reports of research institutes and health care authorities. Direct health care costs were estimated for hospital care, general practice care and paramedical care. These costs were calculated using fees. Calculation of indirect costs (absenteeism and disability) was based on the Human Capital Method (HCM). As an alternative approach the Friction Cost Method (FCM) was used. The total cost of neck pain in The Netherlands in 1996 was estimated to be US $686 million. The share of these costs was about 1% of total health care expenditures and 0.1 % of the Gross Domestic Product (GDP) in 1996. Direct costs were $160 million (23%). Paramedical care accounted for largest proportion of direct costs (84%). When applying the HCM for calculating indirect costs, these costs amounted to $527 million (77%). The total number of sick days related to neck pain were estimated to be 1.4 million with a total cost of $185.4 million in 1996. Disability for neck pain accounted for the largest proportion (50%) of the total costs related to neck pain in 1996 ($341). When applying the FCM for calculating the indirect costs, these costs were reduced to $96 million. The costs related to neck pain in 1996 in The Netherlands were substantial. Some caution should be taken in interpretation, as a number of assumptions had to be made in order to estimate the total costs. The cost structure shown in this study, with high indirect costs, has also been found in other studies. From an economical point of view it seems to be important to prevent patients from having to take sick leave and disability. One way in achieving this goal is to develop and investigate more effective treatments for acute neck pain, in order to prevent patients developing chronic pain and disability. Another option is to protect chronic patients from sick leave and disability by careful management. Thus, also in the area of direct medical costs, there may be room for cost savings by stimulating and improving cost-efficiency and cost-effectiveness of the (para)medical care. In order to deal with the lack of specific disease information, more detailed information of medical consumption, sick leave and disability is required for future cost analysis.

Topical capsaicin in humans: parallel loss of epidermal nerve fibers and pain sensation.

Abstract: Capsaicin applied topically to human skin produces itching, pricking and burning sensations due to excitation of nociceptors. With repeated application, these positive sensory responses are followed by a prolonged period of hypalgesia that is usually referred to as desensitization, or nociceptor inactivation. Consequently, capsaicin has been recommended as a treatment for a variety of painful syndromes. The precise mechanisms that account for nociceptor desensitization and hypalgesia are unclear. The present study was performed to determine if morphological changes of intracutaneous nerve fibers contribute to desensitization and hypalgesia. Capsaicin (0.075%) was applied topically to the volar forearm four times daily for 3 weeks. At various time intervals tactile, cold, mechanical and heat pain sensations were assessed in the treated and in contralateral untreated areas. Skin blisters and skin biopsies were collected and immunostained for protein gene product (PGP) 9.5 to assess the morphology of cutaneous nerves and to quantify the number of epidermal nerve fibers (ENFs). Capsaicin resulted in reduced sensitivity to all cutaneous stimuli, particularly to noxious heat and mechanical stimuli. This hypalgesia was accompanied by degeneration of epidermal nerve fibers as evidenced by loss of PGP 9.5 immunoreactivity. As early as 3 days following capsaicin application, there was a 74% decrease in the number of nerve fibers in blister specimens. After 3 weeks of capsaicin treatment, the reduction was 79% in blisters and 82% in biopsies. Discontinuation of capsaicin was followed by reinnervation of the epidermis over a 6-week period with a return of all sensations, except cold, to normal levels. We conclude that degeneration of epidermal nerve fibers contributes to the analgesia accredited to capsaicin. Furthermore, our data demonstrate that ENFs contribute to the painful sensations evoked by noxious thermal and mechanical stimuli.

Self efficacy as a mediator of the relationship between pain intensity, disability and depression in chronic pain patients.

Abstract: To clarify the relationships between physical, and psychosocial components of chronic pain, a path analytic model was tested conceptualizing self efficacy as a mediator of disability. In turn, disability was hypothesized to mediate depression. This model could help explain the circumstances under which disability develops and why so many chronic pain patients become depressed. Questionnaires from 126 chronic pain patients (without prior depression) were reviewed from three pain clinics. Hypothesized and alternate models were tested using separate regression equations to identified models which best fit these data. Regression analysis supported that self efficacy partially mediates the relationship between pain intensity and disability. This model accounted for 47% of the explained variance in disability ( P R 2 =0.56), with gender and pain location paths remaining significant. In separate regression analyses, disability was found to partially mediate the relationship between pain intensity and depression (b=0.47–0.33). This model accounted for 26% of the explained variance in depression. The addition of self efficacy to this model supported it as a stronger mediator ( R 2 =0.32), and suggested that support for disability as a mediator of depression was a spurious finding. Both pain intensity and self efficacy contribute to the development of disability and depression in patients with chronic pain. Therefore, the lack of belief in ones own ability to manage pain, cope and function despite persistent pain, is a significant predictor of the extent to which individuals with chronic pain become disabled and/or depressed. Nevertheless, these mediators did not eliminate the strong impact that high pain intensity has on disability and depression. Therefore, therapy should target multiple goals, including: pain reduction, functional improvement and the enhancement of self efficacy beliefs.

Topical lidocaine patch relieves postherpetic neuralgia more effectively than a vehicle topical patch: results of an enriched enrollment study

Abstract: This study compared the efficacy of topical lidocaine patches versus vehicle (placebo) patches applied directly to the painful skin of subjects with postherpetic neuralgia (PHN) utilizing an 'enriched enrollment' study design. All subjects had been successfully treated with topical lidocaine patches on a regular basis for at least 1 month prior to study enrollment. Subjects were enrolled in a randomized, two-treatment period, vehicle-controlled, cross-over study. The primary efficacy variable was 'time to exit'; subjects were allowed to exit either treatment period if their pain relief score decreased by 2 or more categories on a 6-item Pain Relief Scale for any 2 consecutive days. The median time to exit with the lidocaine patch phase was greater than 14 days, whereas the vehicle patch exit time was 3.8 days (P < 0.001). At study completion, 25/32 (78.1%) of subjects preferred the lidocaine patch treatment phase as compared with 3/32 (9.4%) the placebo patch phase (P < 0.001). No statistical difference was noted between the active and placebo treatments with regards to side effects. Thus, topical lidocaine patch provides significantly more pain relief for PHN than does a vehicle patch. Topical lidocaine patch is a novel therapy for PHN that is effective, does not cause systemic side effects, and is simple to use.

Chronic motor cortex stimulation in the treatment of central and neuropathic pain. Correlations between clinical, electrophysiological and anatomical data.

Abstract: Thirty-two patients with refractory central and neuropathic pain of peripheral origin were treated by chronic stimulation of the motor cortex between May 1993 and January 1997. The mean follow-up was 27.3 months. The first 24 patients were operated according to the technique described by Tsubokawa. The last 13 cases (eight new patients and five reinterventions) were operated by a technique including localisation by superficial CT reconstruction of the central region and neuronavigator guidance. The position of the central sulcus was confirmed by the use of intraoperative somatosensory evoked potentials. The somatotopic organisation of the motor cortex was established peroperatively by studying the motor responses at stimulation of the motor cortex through the dura. Ten of the 13 patients with central pain (77%) and ten of the 12 patients with neuropathic facial pain had experienced substantial pain relief (75%). One of the three patients with post-paraplegia pain was clearly improved. A satisfactory result was obtained in one patient with pain related to plexus avulsion and in one patient with pain related to intercostal herpes zooster. None of the patients developed epileptic seizures. The position of the stimulating poles effective on pain corresponded to the somatotopic representation of the motor cortex. The neuronavigator localisation and guidance technique proved to be most useful identifying the appropriate portion of the motor gyrus. It also allowed the establishment of reliable correlations between electrophysiological-clinical and anatomical data which may be used to improve the clinical results and possibly to extend the indications of this technique.

Complex regional pain syndrome: are the IASP diagnostic criteria valid and sufficiently comprehensive?

Abstract: This is a multisite study examining the internal validity and comprehensiveness of the International Association for the Study of Pain (IASP) diagnostic criteria for Complex Regional Pain Syndrome (CRPS). A standardized sign/symptom checklist was used in patient evaluations to obtain data on CRPS-related signs and symptoms in a series of 123 patients meeting IASP criteria for CRPS. Principal components factor analysis (PCA) was used to detect statistical groupings of signs/symptoms (factors). CRPS signs and symptoms grouped together statistically in a manner somewhat different than in current IASP/CRPS criteria. As in current criteria, a separate pain/sensation criterion was supported. However, unlike in current criteria, PCA indicated that vasomotor symptoms form a factor distinct from a sudomotor/edema factor. Changes in range of motion, motor dysfunction, and trophic changes, which are not included in the IASP criteria, formed a distinct fourth factor. Scores on the pain/sensation factor correlated positively with pain duration (P<0. 001), but there was a negative correlation between the sudomotor/edema factor scores and pain duration (P<0.05). The motor/trophic factor predicted positive responses to sympathetic block (P<0.05). These results suggest that the internal validity of the IASP/CRPS criteria could be improved by separating vasomotor signs/symptoms (e.g. temperature and skin color asymmetry) from those reflecting sudomotor dysfunction (e.g. sweating changes) and edema. Results also indicate motor and trophic changes may be an important and distinct component of CRPS which is not currently incorporated in the IASP criteria. An experimental revision of CRPS diagnostic criteria for research purposes is proposed. Implications for diagnostic sensitivity and specificity are discussed.

Ultrasound therapy for musculoskeletal disorders: a systematic review.

Abstract: Background: Ultrasound therapy is used frequently to reduce pain and related disability, mainly by physiotherapists. The objective of this review was to evaluate the effectiveness of ultrasound therapy in the treatment of musculoskeletal disorders. Methods: Published reports of randomized clinical trials investigating the effects of ultrasound therapy on pain, disability or range of motion were identified by a systematic search of MEDLINE, EMBASE and the Cochrane databases, supplemented with citation tracking. The quality of methods of all selected publications was assessed systematically by two independent and `blinded' reviewers, using ten validity criteria. Data from the original publications were used to calculate the differences between groups for success rate, pain, disability and range of motion. Statistical pooling was performed if studies were homogeneous with respect to study populations, interventions, outcome measures and timing of follow-up. Results: 38 Studies were included in the review, evaluating the effects of ultrasound therapy for lateral epicondylitis (n=6), shoulder pain (n=7), degenerative rheumatic disorders (n=10), ankle distorsions (n=4), temporomandibular pain or myofacial pain (n=4) and a variety of other disorders (n=7). In 11 out of 13 placebo-controlled trials with validity scores of at least five out of ten points, no evidence of clinically important or statistically significant results was found. Statistical pooling was only feasible for placebo-controlled trials on lateral epicondylitis, and produced a pooled estimate for the difference in success rate of 15% (95% confidence interval −8%–38%). Conclusions: As yet, there seems to be little evidence to support the use of ultrasound therapy in the treatment of musculoskeletal disorders. The large majority of 13 randomized placebo-controlled trials with adequate methods did not support the existence of clinically important or statistically significant differences in favour of ultrasound therapy. Nevertheless, our findings for lateral epicondylitis may warrant further investigation.

Epidemiology of complex regional pain syndrome: a retrospective chart review of 134 patients.

Abstract: Complex regional pain syndrome (CRPS) remains a poorly understood chronic pain disorder. Little data has been published assessing the epidemiology of CRPS (and reflex sympathetic dystrophy, RSD). This study assessed epidemiological variables in 134 CRPS patients evaluated at a tertiary chronic pain clinic in the US, including demographic, health care utilization and legal/workman's compensation measures. In addition, the frequency of physician-imposed immobilization of the CRPS limb was assessed, as was physical examination evidence of myofascial dysfunction. This study found that these patients had seen on average 4.8 different physicians before referral to the pain center and had received an average of five different kinds of treatments both prior to and during pain clinic treatment. The mean duration of CRPS symptoms prior to pain center evaluation was 30 months. Seventeen percent had a lawsuit and 54% had a worker compensation claim related to the CRPS. Fifty-one patients received a bone scan, but only 53% of which were interpreted as consistent with the diagnosis of RSD/CRPS. Forty-seven percent had a history of physician-imposed immobilization, and 56% had a myofascial component present at evaluation. The duration of CRPS symptoms and the involvement of the upper extremity was significantly associated with the presence of myofascial dysfunction. Thus, this study found that most CRPS patients are referred to a pain specialty clinic after several years of symptoms and many failed therapies. The data also suggest the lack of utility of a diagnostic bone scan and highlight the prominence of myofascial dysfunction in a majority of CRPS patients.

Windup leads to characteristics of central sensitization

Abstract: Central sensitization refers to enhanced excitability of dorsal horn neurons and is characterized by increased spontaneous activity, enlarged receptive field (RF) areas, and an increase in responses evoked by large and small caliber primary afferent fibers. Sensitization of dorsal horn neurons often occurs following tissue injury and inflammation and is believed to contribute to hyperalgesia. Windup refers to the progressive increase in the magnitude of C-fiber evoked responses of dorsal horn neurons produced by repetitive activation of C-fibers. In the present study, we tested the hypothesis that windup leads to central sensitization. Recordings were made from rat nociceptive dorsal horn neurons classed as wide dynamic range. Windup was produced by conditioning stimuli in a train of 12 electrical pulses (0.5 ms duration) applied to the RF at intensities three times the threshold for excitation of C-fibers and at a frequency of 0.5 Hz. Single electrical stimuli applied outside the RF never evoked responses except when delivered following conditioning stimulation inside the RF, indicating an expansion of the RF following windup. C-Fiber conditioning stimuli applied outside the RF also increased the response evoked by a single stimulus and increased the total number of spikes evoked by a train of electrical stimuli delivered inside the RF. Although both A- and C-fibers were activated, conditioning stimuli did not alter subsequent responses evoked by stimulation of A-fibers. Enhanced responsivity to C-fiber input following windup produced by stimulation inside the RF at a frequency of 0.5 Hz could be maintained for approximately 100 s by stimuli delivered at 0.1 Hz, a frequency that itself cannot produce windup. It is concluded that neuronal events leading to windup also produce some of the classical characteristics of central sensitization including expansion of RFs and enhanced responses to C- but not A-fiber stimulation. Thus, windup may be a useful tool to study mechanisms underlying certain characteristics of central sensitization related to C-fiber activity.

A comparison of faces scales for the measurement of pediatric pain: children's and parents' ratings.

Abstract: Faces scales have become the most popular approach to eliciting children's self-reports of pain, although different formats are available. The present study examined: (a) the potential for bias in children's self-reported ratings of clinical pain when using scales with smiling rather than neutral 'no pain' faces; (b) levels of agreement between child and parent reports of pain using different faces scales; and (c) preferences for scales by children and parents. Participants were 75 children between the ages of 5 and 12 years undergoing venepuncture, and their parents. Following venepuncture, children and parents independently rated the child's pain using five different randomly presented faces scales and indicated which of the scales they preferred and why. Children's ratings across scales were very highly correlated; however, they rated significantly more pain when using scales with a smiling rather than a neutral 'no pain' face. Girls reported significantly greater levels of pain than boys, regardless of scale type. There were no age differences in children's pain reports. Parents' ratings across scales were also highly correlated; however, parents also had higher pain ratings using scales with smiling 'no pain' faces. The level of agreement between child and parent reports of pain was low and did not vary as a function of the scale type used; parents overestimated their children's pain using all five scales. Children and parents preferred scales that they perceived to be happy and cartoon-like. The results of this study indicate that subtle variations in the format of faces scales do influence children's and parents' ratings of pain in clinical settings.

Tramadol relieves pain and allodynia in polyneuropathy: A randomised, double-blind, controlled trial

Abstract: It is generally believed that opioids relieve neuropathic pain less effectively than nociceptive pain and that they have no effect on some of the key characteristics of neuropathic pain such as touch-evoked pain (allodynia). Tramadol is an analgesic drug acting directly on opioid receptors and indirectly on monoaminergic receptor systems. The aim of this trial was to determine whether tramadol relieved painful polyneuropathy and reduced allodynia. The study design was randomised, double-blind, placebo-controlled and cross-over. After baseline observations, 45 patients were assigned to one of the two treatment sequences. The dose of tramadol slow-release tablets was titrated to at least 200 mg/day and at highest 400 mg/day. During the two treatment periods of 4 weeks duration, patients rated pain, paraesthesia and touch-evoked pain by use of 0-10 point numeric rating scales. Mechanical allodynia induced by stimulation with an electronic toothbrush was rated at the end of each treatment period with a similar scale. Thirty-four patients completed the study. Their ratings for pain (median 4 vs. 6, P=0.001), paraesthesia (4 vs. 6, P=0.001) and touch-evoked pain (3 vs. 5, P /=50% pain relief was 4.3 (95% confidence interval 2.4-20). It is concluded that tramadol appears to relieve both ongoing pain symptoms and the key neuropathic pain feature allodynia in polyneuropathy.

Generalised muscular hyperalgesia in chronic whiplash syndrome.

Abstract: The whiplash syndrome has immense socio-economic impact. Despite extensive studies over the past years, the mechanisms involved in maintaining the pain in chronic whiplash patients are poorly understood. The aim of the present experimental study was to examine the muscular sensibility in areas within and outside the region involved in the whiplash trauma. Eleven chronic whiplash patients and 11 sex and age matched control subjects were included in the study. Before the experiment, the whiplash patients had pain in the neck and shoulder region with radiating pain to the arm. Five patients reported pain that was more widespread. The somatosensory sensibility in the areas over the infraspinatus, brachioradial, and anterior tibial muscles was assessed by pressure stimulation, pin-prick stimulation, and cotton swap stimulation. Infusion of hypertonic saline (5.85%, 0.5 ml) into the infraspinatus and anterior tibial muscles was performed to assess the muscular sensibility and referred pain pattern. The saline-induced muscle pain intensity was assessed on a continuous visual analogue scale (VAS). The distribution of pain was drawn on an anatomical map. The pressure pain thresholds were significantly lower in patients (P<0. 01) compared with controls: infraspinatus (mean 152.2 vs. 172.7 kPa), brachioradial (mean 70.0 vs. 363.8 kPa), and anterior tibial muscle (mean 172.7 vs. 497.8 kPa). The skin sensibility to pin-prick stimulation and cotton swap stimulation was not different between patients and controls. Infusion of hypertonic saline caused significantly higher VAS scores with longer duration in patients compared to control subjects (P<0.01). The area under the VAS-time curve was significantly (P<0.01) increased in patients compared to control subjects after injection into the infraspinatus muscle (mean 4138.1 vs. 780.0 cm s) and anterior tibial muscle (mean 4370.8 vs. 978.7 cm s). The saline infusion caused local pain defined as pain located around the injection site and referred pain areas not included in the local pain area. The area of local and referred pain were significantly larger in patients compared to control subjects (P<0.01). In the control group, the referred pain areas to infusion of hypertonic saline into the anterior tibial muscle were found at the dorsal aspect of the ankle. In contrast, the areas of referred pain were quite widespread in the patient group with both distal and proximal referred pain areas. In the present study, muscular hyperalgesia and large referred pain areas were found in patients with chronic whiplash syndrome compared to control subjects both within and outside the traumatised area. The findings suggest a generalised central hyperexcitability in patients suffering from chronic whiplash syndrome. This indicates that the pain might be considered as a neurogenic type of pain, and new pharmacological treatments should be investigated accordingly.

Gabapentin and pregabalin, but not morphine and amitriptyline, block both static and dynamic components of mechanical allodynia induced by streptozocin in the rat.

Abstract: A single injection of streptozocin (50 mg/kg, i.p.) led to the development of static and dynamic allodynia in the rat. The two responses were detected, respectively, by application of pressure using von Frey hairs or lightly stroking the hind paw with a cotton bud. Static allodynia was present in the majority of the animals within 10 days following streptozocin. In contrast, dynamic allodynia took almost twice as long to develop and was only present in approximately 60% of rats. Morphine (1-3 mg/kg, s.c.) and amitriptyline (0.25-2.0 mg/kg, p.o.) dose-dependently blocked static allodynia. However, neither of the compounds was effective against dynamic allodynia. In contrast, gabapentin (10-100 mg/kg, p.o.) and the related compound pregabalin (3-30 mg/kg, p.o.) dose-dependently blocked both types of allodynia. However, the corresponding R-enantiomer (10-100 mg/kg, p.o.) of pregabalin, was found to be inactive. The intrathecal administration of gabapentin dose-dependently (1-100 microg/animal) blocked both static and dynamic allodynia. In contrast, administration of similar doses of gabapentin into the hind paw failed to block these responses. It is suggested that in this model of neuropathic pain dynamic allodynia is mediated by A beta-fibres and the static type involves small diameter nociceptive fibres. These data suggest that gabapentin and pregabalin possess a superior antiallodynic profile than morphine and amitriptyline, and may represent a novel class of therapeutic agents for the treatment of neuropathic pain.

Pain report and the relationship of pain to physical factors in the first 6 months following spinal cord injury.

Abstract: A prospective, longitudinal study of 100 people with traumatic spinal cord injury (SCI) was performed to determine the time of onset, prevalence and severity of different types of pain (musculoskeletal, visceral, neuropathic at level, neuropathic below level) at 2, 4, 8, 13 and 26 weeks following SCI. In addition, we sought to determine the relationship between physical factors such as level of lesion, completeness and clinical SCI syndrome and the presence of pain. At 6 months following SCI, 40% of people had musculoskeletal pain, none had visceral pain, 36% had neuropathic at level pain and 19% had neuropathic below level pain. When all types of pain were included, at 6 months following injury, 64% of people in the study had pain, and 21% of people had pain that was rated as severe. Those with neuropathic below level pain were most likely to report their pain as severe or excruciating. There was no relationship between the presence of pain overall and level or completeness of lesion, or type of injury. Significant differences were found, however, when specific types of pain were examined. Musculoskeletal pain was more common in people with thoracic level injuries. Neuropathic pain associated with allodynia was more common in people who had incomplete spinal cord lesions, cervical rather than thoracic spinal cord lesions, and central cord syndrome. Therefore, this study suggests that most people continue to experience pain 6 months following spinal cord injury and 21% of people continue to experience severe pain. While the presence or absence of pain overall does not appear to be related to physical factors following SCI, there does appear to be a relationship between physical factors and pain when the pain is classified into specific types.

Randomised clinical trial comparing the effects of acupuncture and a newly designed placebo needle in rotator cuff tendinitis.

Abstract: Acupuncture has gained increasing attention in the treatment of chronic pain. The lack of a satisfying placebo method has made it impossible to show whether needling is an important part of the method or whether the improvement felt by the patient is due to the therapeutic setting and psychological phenomena. Also, the effectiveness of acupuncture has not been demonstrated sufficiently. We treated 52 sportsmen with rotator cuff tendinitis in a randomised single-blind clinical trial using a new placebo-needle as control. Patients were treated for 4 weeks. The primary endpoint of the trial was the change in the modified Constant-Murley-score from the baseline. Assessment of the treatment outcome was made by experienced orthopaedists not informed of the treatment allocation. Acupuncture with penetration of the skin was shown to be more effective than a similar therapeutic setting with placebo needling in the treatment of pain. The acupuncture-group improved 19.2 Constant-Murley-score points (SD 16.1, range from −13 to 50), the control-group improved 8.37 points (SD 14.56, range from −20 to 41), (P=0.014; C.I. 2.3;19.4). This study showed that needling is an important part of the acupuncture effect in the treatment of chronic shoulder pain in athletes. No conclusions can be derived from this study concerning the importance of choosing points and the rules of Traditional Chinese Medicine. Using the new placebo method as control for other ailments could improve the evidence of specific acupuncture effects beyond pain treatment.