Consensus and Controversies Between Pain and Addiction Experts on the Prevention, Diagnosis, and Management of Prescription Opioid Use Disorder.

OBJECTIVES: Prescription opioid use disorder (POUD) is an established public health crisis in many countries, and current evidence indicates it is a growing problem in Europe. Many specialists play a role, including pain and addiction medicine specialists, in the diagnosis and management of POUD, but neither group can fully address these patients' needs alone. The purpose of this consensus process was to bring together experts from pain and addiction medicine to examine the positions of both specialties. METHODS: In all, 13 international pain medicine, addiction medicine, and addiction psychiatry experts convened a meeting to formulate a set of consensus statements on the diagnosis and management of POUD. The statements were further refined by a wider group of 22 European expert clinicians. At a second meeting of all 35 participants, a set of controversy statements was also developed to recognize some of the key areas of divergent opinion. RESULTS/CONCLUSIONS: There was a high level of agreement between pain and addiction specialists. Key themes that emerged were the need to strengthen interdisciplinary communication, a desire for greater education and training for clinicians in both specialties, and mutual acknowledgment of the importance of multidisciplinary management of POUD. The blurred line between poorly managed pain and POUD was also a subject of much discussion, reflecting the difficulties in defining and diagnosing this complex condition.

Prevalence and Determinants of Painful and Painless Neuropathy in Type 1 Diabetes Mellitus.

Aims: To evaluate (1) the prevalence of diabetic distal symmetrical sensory-motor polyneuropathy (DSPN) and painful DSPN among patients with type 1 diabetes mellitus (DM1) aged over 18 years and (2) the determinant factors of neuropathy and pain in those patients. Materials and Methods: An epidemiological, cross-sectional, observational study was performed; 330,386 people were included, and a total of 444 people were diagnosed with DM1. After exclusion of possible confounders, 360 patients were assessed for painless and painful DSPNs using neurological examination and questionnaires for neuropathy and pain. Odds ratio (OR) and confidence intervals (95% CI) were estimated using multinomial logistic regression models. The analysis was based on a framework with four conceptual levels that consider feasible pathways between several risk factors: (1) socio-demographic factors and diabetes duration, (2) patient habits, (3) co-morbidities, and (4) metabolic factors and disease complications. Results: The prevalence of DSPN and painful DSPN were 42.8 and 18.9%, respectively. Diabetes duration was positively associated with painful (OR = 1.107, 95% CI: 1.107-1.139) and painless DSPN (OR = 1.069, 95% CI: 1.043-1.096). Education level was negatively associated with painful DSPN (OR = 0.889, 95% CI: 0.826-0.957). Sex (female) was positively associated only with painless DSPN (OR = 1.769, 95% CI: 1.007-3.107). Being a current or former smoker was positively associated only with painless DSPN (OR = 1.940, 95% CI: 1.069-3.518). Hypertension was positively associated with painful DSPN (OR = 2.474, 95% CI: 1.110-5.512) and painless DSPN (OR = 2.565, 95% CI: 1.252-5.256). Glycated hemoglobin (HbA1c) was positively associated only with painless DSPN (OR = 1.193, 95% CI: 1.018-1.399). Conclusions: Diabetes duration and hypertension have a direct impact on the development of painful and painless DSPN. However, female sex and HbA1c have a direct effect only on the development of painless DSPN, and education level has an indirect effect on the development of painful DSPN. Therefore, it can be concluded that different etiological factors have different contributions to the development of neuropathy and pain.

Psychological Predictors of Acute Postoperative Pain After Hysterectomy for Benign Causes.

OBJECTIVES: Psychological parameters have been shown to contribute significantly to the development of acute postoperative pain (APOP). For the prediction of APOP in chest malformation patients and cancer patients, we found pain-specific psychological predictors to be of higher relevance than general psychological predictors. The current study aims to further substantiate these findings. MATERIALS AND METHODS: In a sample of 73 middle-aged hysterectomy patients, 3 predictor sets were assessed 1 day before surgery: attentional biases (toward pain-related, social threat, and positive words in a dot-probe task), pain-related emotions and cognitions (pain anxiety, pain catastrophizing, and pain hypervigilance), and affective state variables (depression and somatization). APOP intensity rated 2 to 3 days after surgery and analgesic consumption during the first 48 postoperative hours were used as outcome measures. RESULTS: APOP intensity ratings were significantly explained by their best single predictors in a multiple regression analysis: social threat words of the dot-probe task, pain anxiety, and somatization (14.7% of explained variance). When comparing standardized ß coefficients, pain-specific psychological predictors appeared to be of higher explanatory relevance than general psychological predictors. In contrast, analgesic consumption could not be significantly predicted by the psychological variables. DISCUSSION: Hysterectomy patients at risk for high APOP intensity could be characterized by the psychological variables used, whereas their predictive value for analgesic consumption was limited. The high predictive potency of pain-specific psychological variables should be considered for further improvement of pain management and prevention, because pain-specific variables such as pain anxiety can be the target of focal psychological interventions when preparing for surgery.

Association of genetic and psychological factors with persistent pain after cosmetic thoracic surgery.

The genetic control of pain has been repeatedly demonstrated in human association studies. In the present study, we assessed the relative contribution of 16 single nucleotide polymorphisms in pain-related genes, such as cathechol-O-methyl transferase gene (COMT), fatty acid amino hydrolase gene (FAAH), transient receptor potential cation channel, subfamily V, member 1 gene (TRPV1), and δ-opioid receptor gene (OPRD1), for postsurgical pain chronification. Ninety preoperatively pain-free male patients were assigned to good or poor outcome groups according to their intensity or disability score assessed at 1 week, 3 months, 6 months, and 1 year after funnel chest correction. The genetic effects were compared with those of two psychological predictors, the attentional bias toward positive words (dot-probe task) and the self-reported pain vigilance (Pain Vigilance and Awareness Questionnaire [PVAQ]), which were already shown to be the best predictors for pain intensity and disability at 6 months after surgery in the same sample, respectively. Cox regression analyses revealed no significant effects of any of the genetic predictors up to the end point of survival time at 1 year after surgery. Adding the genetics to the prediction by the attentional bias to positive words for pain intensity and the PVAQ for pain disability, again no significant additional explanation could be gained by the genetic predictors. In contrast, the preoperative PVAQ score was also, in the present enlarged sample, a meaningful predictor for lasting pain disability after surgery. Effect size measures suggested some genetic variables, for example, the polymorphism rs1800587G>A in the interleukin 1 alpha gene (IL1A) and the COMT haplotype rs4646312T>C/rs165722T>C/rs6269A>G/rs4633T>C/rs4818C>G/rs4680A>G, as possible relevant modulators of long-term postsurgical pain outcome. A comparison between pathophysiologically different predictor groups appears to be helpful in identifying clinically relevant predictors of chronic pain.

Searching for success: Development of a combined patient-reported-outcome ("PRO") criterion for operationalizing success in multi-modal pain therapy.

BACKGROUND: There is a need for a way to measure success in multi-modal pain therapy that researchers and clinicians can agree upon. According to developments in health services research, operationalizing success should take patient-reported outcomes into account. We will present a success criterion for pain therapy that combines different patient-reported variables and includes validity measures. The usable criterion should be part of a statistically significant and satisfactory model identifying predictors of successful pain therapy. METHODS: Routine data from 375 patients treated with multi-modal pain therapy from 2008 to 2013 were used. The change scores of five constructs were used for the combined success criterion: pain severity, disability due to pain, depressiveness, and physical- and mental-health-related quality of life. According to the literature, an improvement of at least ½ standard deviation was required on at least four of the five constructs to count as successful. A three-step analytical approach including multiple binary logistic regression analysis was chosen to identify the predictors of therapy success with the success criterion as the dependent variable. RESULTS: A total of 58.1% of the patients were classified as successful. Convergent and predictive validity data show significant correlations between the criterion and established instruments, while discriminative validity could also be shown. A multiple binary logistic regression analysis confirmed the feasibility; a significant model (Chi(2) (8) = 52.585; p < .001) that explained 17.6% of the variance identified the following predictors of therapy success: highest pain severity in the last 4 weeks, disability due to pain, and number of physician visits in the last 6 months. CONCLUSIONS: It is possible to develop a feasible success criterion that combines several variables and includes patient-reported outcomes ("PROs") with routine data that can be used in a predictor analysis in multi-modal pain therapy. The criterion was based on basic constructs used in pain therapy and used widespread validated self-rating instruments. Thus, it should be easy to transfer this criterion to other institutions.

Treatment of localized neuropathic pain of different etiologies with the 5% lidocaine medicated plaster - a case series.

OBJECTIVE: To assess the efficacy and safety of the topical 5% lidocaine medicated plaster in the treatment of localized neuropathic pain. STUDY DESIGN: This was a case series at an Austrian pain clinic, using retrospective analysis. PATIENTS AND METHODS: Data of 27 patients treated for localized neuropathic pain with the 5% lidocaine medicated plaster were retrospectively analyzed. Assessment included changes in overall pain intensity, in intensity of different pain qualities, and of hyperalgesia and allodynia, and changes in sleep quality. RESULTS: Patients (17 female, ten male; mean age 53.4±11.4 years) presented mainly with dorsalgia (16 patients) or postoperative/posttraumatic pain (seven patients); one patient suffered from both. The mean overall pain intensity prior to treatment with lidocaine medicated plaster was 8.4±1.2 on the 11-point Likert scale. In the majority of cases, the lidocaine plaster was applied concomitantly with preexisting pain medication (81.5% of the patients). During the 6-month observation period, overall mean pain intensity was reduced by almost 5 points (4.98) to 3.5±2.6. Substantial reductions were also observed for neuralgiform pain (5 points from 7.9±2.6 at baseline) and burning pain (3 points from 5.2±4.1). Sleep quality improved from 4.6±2.6 at baseline to 5.5±1.8. Stratification by pain diagnosis showed marked improvements in overall pain intensity for patients with dorsalgia or postoperative/posttraumatic pain. The lidocaine plaster was well tolerated. CONCLUSION: Overall, topical treatment with the 5% lidocaine medicated plaster was associated with effective pain relief and was well tolerated.

Does severe acute pain provoke lasting changes in attentional and emotional mechanisms of pain-related processing? A longitudinal study.

Pain experiences, learning, and genetic factors have been proposed to shape attentional and emotional processes related to pain. We aimed at investigating whether a singular major pain experience also changes cognitive-emotional processing. The influence of acute postoperative pain after cosmetic surgery of the thorax was tested in 80 preoperatively pain-free male individuals. Acute pain was measured as independent variable during the first week postsurgery by pain intensity ratings and the requested analgesic boluses (Patient-Controlled Epidural Analgesia (PCEA)). Pain catastrophizing (Pain Catastrophizing Scale (PCS)), pain anxiety (Pain Anxiety and Symptom Scale (PASS)), pain hypervigilance (Pain Vigilance and Awareness Questionnaire (PVAQ)), and attentional biases to emotionally loaded stimuli (including pain) in a dot-probe task were assessed 1 week, 3 months, and 6 months postsurgery as dependent variables. Hierarchical regression analyses were performed to test whether the 2 acute pain parameters can predict these cognitive-emotional variables. As a rigorous test, significant prediction was required in addition to the prediction of the dependent variables by themselves with lag-1. Acute pain (mainly the pain ratings) appeared to be a significant predictor for PCS, PASS, and PVAQ 1 week after surgery (deltaR(2) = [8.7% to 11.3%]). In contrast, the attentional biases in the dot-probe task could not be predicted by the pain ratings. The levels of pain catastrophizing and pain hypervigilance increased in the acute phase after surgery when influenced by acute pain and declined, along with pain anxiety, during the next 3 months. In conclusion, a one-time intense pain experience, such as acute postoperative pain, appeared to produce at least short-lived changes in the attentional and emotional processing of pain.

Chronic opioid use is associated with increased DNA methylation correlating with increased clinical pain.

Environmentally caused changes in chromosomes that do not alter the DNA sequence but cause phenotypic changes by altering gene transcription are summarized as epigenetics. A major epigenetic mechanism is methylation or demethylation at CpG-rich DNA islands. DNA methylation triggered by drugs has largely unexplored therapeutic consequences. Here we report increased methylation at a CpG rich island in the OPRM1 gene coding for µ-opioid receptors and at a global methylation site (LINE-1) in leukocytes of methadone-substituted former opiate addicts compared with matched healthy controls. Higher DNA methylation associated with chronic opioid exposure was reproduced in an independent cohort of opioid-treated as compared to non-opioid-treated pain patients. This suggests that opioids may stimulate DNA methylation. The OPRM1 methylation had no immediate effect on µ-opioid receptor transcription and was not associated with opioid dosing requirements. However, the global DNA methylation at LINE-1 was significantly correlated with increased chronic pain. This suggests inhibitory effects on the transcription of still unspecified nocifensive gene products. It further implies that opioids may be causally associated with increased genome-wide DNA methylation, although currently there is no direct evidence of this. This has phenotypic consequences for pain and may provide a new, epigenetics-associated mechanism of opioid-induced hyperalgesia. The results indicate a potential influence of opioid analgesics on the patients' epigenome. They emphasize the need for reliable and cost-effective screening tools and may imply that high-throughput screening for lead compounds in artificial expression systems may not provide the best tools for identifying new pain medications.

Treatment of localized neuropathic pain after disk herniation with 5% lidocaine medicated plaster.

OBJECTIVE: To assess treatment with the 5% lidocaine medicated plaster for peripheral neuropathic pain after disk herniation. STUDY DESIGN: Case series, single center, retrospective data. PATIENTS AND METHODS: Data of 23 patients treated for neuropathic pain with the lidocaine plaster for up to 24 months after a protrusion or prolapse of the cervical, thoracic, or lumbar vertebral disks were retrospectively analyzed. Changes in overall pain intensity, in intensity of different pain qualities and of allodynia and hyperalgesia were evaluated. RESULTS: Patients (14 female/nine male, mean age 53.5 ± 10.4 years) presented with radiating pain into the abdomen, back, neck, shoulder, or legs and feet with a mean pain intensity of 8.3 ± 1.5 on the 11-point Likert scale. Mean treatment duration was 7.6 months; 52% of the patients received lidocaine plaster as monotherapy. At the end of the observation, mean overall pain intensity had been reduced to 3.1 ± 1.8. All other parameters also improved. The treatment was well tolerated. CONCLUSION: These results point to a safe and effective treatment approach with 5% lidocaine medicated plaster for localized neuropathic pain related to disk herniation. However, owing to the small sample size, further investigation in a larger-scale controlled trial is warranted.

Pain Management and Symptom-Oriented Drug Therapy in Palliative Care.

SUMMARY: Patients with advanced life-limiting disease often suffer from symptoms that considerably impair their quality of life and that of their families. Palliative care aims to alleviate these symptoms by a multidimensional approach. Pharmacotherapy is an essential component. The objective of this review is to give an overview of symptom-oriented drug therapy for the most important symptoms in palliative care. Leading symptoms that affect quality of life include pain, dyspnea, nausea and emesis, weakness and disorientation. Careful examination and history taking help to understand the individual mechanisms underlying these symptoms. Specific pharmacotherapy provides an efficient way to achieve symptom control in the context of palliative care.

Attentional and emotional mechanisms related to pain as predictors of chronic postoperative pain: a comparison with other psychological and physiological predictors.

The present prospective longitudinal study on chronic postoperative pain was conducted to assess the predictive power of attentional and emotional variables specifically assumed to augment pain, such as pain hypervigilance, pain-related anxiety, pain catastrophizing and attentional biases to pain. Their relevance was determined in comparison with other psychological and physiological predictors (depression, anxiety, somatization, cortisol reactivity, pain sensitivity). In 84 young male patients the predictor variables were assessed one day before surgery (correction of chest malformation). Postoperative outcome (subjective pain intensity and pain-related disability) was assessed three (N=84) and six months (N=78) after surgery. Patients were classified into good and poor outcome groups. Patients with high pain intensity three (25%) or six months (14%) after surgery, differed significantly from those low in pain with regard to their preoperative performance in the dot-probe task (high attentional bias towards positive words). A sizeable portion (54%) of patients still felt disabled due to pain after three months and a few patients after six months (13%). These patients were those with high preoperative ratings in the Pain Vigilance and Awareness Questionnaire. The few subjectively disabled patients after six months could be identified in addition by low pressure pain and high cold pain thresholds before surgery. An attentional bias towards positive stimuli prior to surgery may indicate a maladaptive coping style, which avoids necessary confrontation with pain and predisposes patients to chronic postoperative pain. Lasting subjectively felt pain-related disability occurs predominantly in patients with high levels of pain hypervigilance before surgery.

Higher pain scores, similar opioid doses and side effects associated with antipyretic analgesics in specialised tertiary pain care.

PURPOSE: To evaluate whether non-opioid antipyretic analgesics are associated with lower pain scores, opioid doses and side effects in pain patients in tertiary care. METHODS: In a cross-sectional observational study, data from 519 Caucasians (197 men, 322 women; mean age 55.6 ± 15 years) who had undertaken pain therapy for various causes for 77.5 ± 90.8 months, obtained in three separate study centres, was analysed for actual 24-h pain scores, daily opioid doses and the occurrence of side effects. RESULTS: Of the 519 patients, 352 received opioids and 260 antipyretic analgesics, from whom 154 received both classes and 304 only either class. The administration of non-opioid antipyretic analgesics was associated with higher average pain scores (4.6 ± 2.5 vs 3.9 ± 2.6; P = 0.01), tendentially higher average oral morphine equivalent doses (121.8 ± 162.2 vs 146.7 ± 242.4 mg/d; P = 0.25) and a similar incidence of side effects (P = 0.21). These results were correspondingly seen when analysing the three study centres separately as independent cohorts. CONCLUSIONS: With the caution advised for cross-sectional data, the results dispute a clinical benefit of non-opioid antipyretic analgesics for most chronic pain patients in tertiary care and draw attention towards prospectively re-evaluating the utility of non-opioid antipyretic analgesics in tertiary pain care in a randomised placebo controlled trial.

Long-term treatment of neuropathic pain with a 5% lidocaine medicated plaster.

BACKGROUND AND OBJECTIVE: The 5% lidocaine medicated plaster is a topical treatment for peripheral neuropathic pain symptoms (e.g. burning, shooting and stabbing pain) and is registered for the treatment of postherpetic neuralgia. This study examined the efficacy and tolerability of long-term treatment with the 5% lidocaine medicated plaster in patients with localized neuropathic pain conditions. METHODS: Twenty patients with localized neuropathic pain [postoperative neuropathic pain (n = 14); complex regional pain syndrome (n = 2); and postherpetic neuralgia (n = 4)], who had been successfully treated with 5% lidocaine medicated plaster, were followed up by telephone interview after 3 and 5 years. Questions were related to the efficacy, development of tolerance, tolerability, wear time and comfort of the plaster. RESULTS: At 3 years, 10 out of 20 (50%) initial responders were still using the plasters with no decline in analgesic efficacy. After 5 years, eight of the original 20 responders (40%) maintained treatment and continued to experience effective pain relief. The 12 responders who discontinued treatment did so because they no longer required analgesic therapy (n = 4); their health insurer refused to fund treatment (n = 2); they were lost to follow-up (n = 1); or had died from an illness unrelated to plaster treatment (n = 5). No patient discontinued because of inadequate analgesia or intolerable side effects. Reversible erythema occurred in two patients wearing the plaster for more than 16 h. There were no systemic side effects. CONCLUSION: The 5% lidocaine medicated plaster provides sustained pain relief over long-term treatment in patients with neuropathic pain of various causes and is well tolerated.

Cross-sectional assessment of the consequences of a GTP cyclohydrolase 1 haplotype for specialized tertiary outpatient pain care.

OBJECTIVES: Reduced-function variants of the guanosine triphosphate cyclohydrolase gene (GCH1) have been associated with reduced pain in well-defined cohorts of patients and healthy volunteers. We addressed the question whether this genetic association plays a role in outpatient pain therapy. METHODS: In a cross-sectional observational study, 523 patients were enrolled in 3 different tertiary care outpatient pain centers at German University hospitals. Of the 519 Caucasian patients, data from 424 could be analyzed for functional associations of the formerly named "pain-protective" GCH1 haplotype with the key characteristics of pain therapy being (1) actual pain, (2) opioid dosing, and (3) pain therapy duration. RESULTS: With an allelic frequency of 14.2% the pain-protective haplotype was not rarer among pain patients than in the general population (P=0.344). However, a tendency toward gene dose-dependent effects of the GCH1 haplotype was observed in all the 3 therapy parameters. Carriers of the haplotype tended to have lower actual 24-hour pain scores (n=424; P=0.18), require lower opioid doses (P=0.096), and were significantly shorter on specialized pain therapy (P=0.004). The latter applied predominantly to differences between homozygous carriers and heterozygous (alpha-corrected t test: P=0.06) or non-carriers (P=0.011) of the haplotype. CONCLUSIONS: The results strength the support for a modest yet reproducible and consistent pain-protective effect associated with a GCH1 haplotype known to reduce GCH1 and thus BH4 up-regulation. Pending independent verification, the results might point to a prophylactic role of decreased GCH1 up-regulation delaying the need for pain therapy.

Cross-sectional analysis of the influence of currently known pharmacogenetic modulators on opioid therapy in outpatient pain centers.

AIM: A finite number of variants in the OPRM1, COMT, MC1R, ABCB1 and CYP2D6 genes has been identified to significantly modulate the effects of opioids in controlled homogenous settings. We analyzed the imprint of these variants in opioid therapy in a highly variable cohort of pain patients treated in outpatient units to test whether genotyping may play a role in this clinical setting. METHODS: In a multicenter study conducted in tertiary care outpatient pain centers, 352 patients (156 men and 196 women, aged 58.5+/- 14.6 years) treated for 1-600 months (63.4 +/- 92.4 months) with various opioids for pain of various origins were included. Genotyping was performed for all the variants reportedly modulating pain in well-defined cohorts. Association analyses focused on opioid dosing, the actual 24-h pain score on a 0-10 rating scale and the occurrence of side effects. RESULTS: The frequency of the genetic variants in the patients did not significantly differ from that in the average Caucasian population. Daily opioid doses ranged from 4 to 1750 mg oral morphine equivalents (133.4 +/- 203.2 mg) and significantly decreased in a gene dose-dependent manner with the P-glycoprotein variant ABCB1 3435C>T. Pain was rated on average at 3.7 +/- 2.6. There was a tendency towards increased pain in a gene dose-dependent manner with the mu-opioid receptor variant OPRM1 118A>G. CONCLUSION: Genetics were reflected in the outpatient pain therapy only to a modest degree. The need of outpatient therapy of pain of various causes guided by the presently known functional genetic variants cannot be convincingly concluded from the present data. Using the ABCB1 3435 genotype to predefine lower individual opioid doses barely merits the laboratory effort. If any, the results suggest that a genetics guided outpatient pain therapy may be based on ABCB1 and OPRM1 variants.

Effectiveness of an intensive multidisciplinary headache treatment program.

OBJECTIVE: To investigate if the effectiveness of a 96-hour multidisciplinary headache treatment program exceeds the effectiveness of a 20-hour program and primary care. BACKGROUND: When dealing with chronic back pain, low-intensity multidisciplinary treatment yields no significantly better results than standard care and monodisciplinary therapy; however, high-intensity treatment does. For multidisciplinary headache treatment, such comparisons are not yet available. In a previous study undertaken by our Pain Center, the outcome of a minimal multidisciplinary intervention model (20-hour) did not exceed primary care. METHODS: Forty-two patients suffering from frequent headaches (20 +/- 9 headache days/month; range: 8-30) were treated and evaluated in a 96-hour group program. The results were compared with the outcomes of the previous study. Subjects who had undergone either the 20-hour multidisciplinary program or the primary care were used as historical control groups. FINDINGS: A significant reduction in migraine days (P < .001), tension-type headache days (P < .001), frequency of migraine attacks (P = .004), and depression score (P < .001) was seen at the follow-up after 22 (+/-2) weeks. Comparing the intensive multidisciplinary program with primary care, repeated measures ANOVAs revealed significant time x group interactions for migraine days (P = .020), tension-type headache days (P = .016), and frequency of migraine attacks (P = .016). In comparison with the 20-hour multidisciplinary program, the 96-hour program showed significantly better effects only in the reduction of migraine days (P = .037) and depression score (P = .003). The responder-rates (> or =50% improvement) in the 96-hour program were significantly higher than in the 20-hour program (migraine days, P = .008; tension-type headache days, P = .044) and primary care (migraine days, P = .007; tension-type headache days, P = .003; tension-type headache intensity, P = .037). The effect sizes were small to medium in the 96-hour program. Particularly with the reduction of migraine symptomatology, the 96-hour program performed better than the 20-hour program, which produced only negligible or small effects. CONCLUSIONS: Intensive multidisciplinary headache treatment is highly effective for patients with chronic headaches. Furthermore, migraine symptomatology responds especially well to this intensive treatment program, whereas effects on tension-type headaches were realized by both multidisciplinary programs. Randomized controlled trials and subgroup analysis are needed to find out if these results can be replicated and which patient characteristics allow for sufficient improvements for headache sufferers even with less complex treatment.

Hypervigilance as predictor of postoperative acute pain: its predictive potency compared with experimental pain sensitivity, cortisol reactivity, and affective state.

OBJECTIVES: Pain hypervigilance--a strong attentional bias toward pain--is thought to accompany chronic pain and modulate pain management. Its usefulness as predisposing factor for the development and maintenance of pain has been discussed. The aim of our study was to demonstrate the predictive power of hypervigilance for the development of acute postoperative pain. METHODS: Fifty-four young male patients were assessed 1 day before surgery (correction of chest malformation) on a range of psychologic predictors. These predictors included the assessment of hypervigilance (questionnaires as the Pain Catastrophizing Scale, Pain Anxiety Symptom Scale, the Pain Vigilance and Awareness Questionnaire, and the dot-probe task) and affective state, experimental pain sensitivity, and cortisol reactivity. Acute postoperative pain was assessed by ratings of pain intensity 1 week postsurgery and through the amount of analgesics [patient-controlled epidural analgesia (PCEA)] requested during the first days after surgery. RESULTS: Pain intensity was significantly explained (17% explained variance) by hypervigilance, whereas PCEA performance was not (10%). Adding all other predictors led to a significant increase of explained variance (35%) for pain ratings and a nonsignificant increase (19%) for PCEA. A more parsimonious solution with only heat pain threshold added led to a significant increase in explained variance (30%) for pain intensity. Hypervigilance was only moderately correlated with the other predictors. DISCUSSION: Hypervigilance proved to be a powerful predictor of subjective acute postoperative pain, but was less useful with regard to the amount of requested analgesics. The overlap with other psychologic predictors (affective state, experimental pain sensitivity, and cortisol reactivity) is sufficiently small to consider hypervigilance a promising supplement in psychologic predictor research.

Use of patient-controlled analgesia for pain control in dying children.

BACKGROUND: In the last week of life, the daily opioid dose in children is highly variable, making the use of patient-controlled analgesia (PCA) a useful therapy option. Scientific data on the use of PCA in paediatric palliative care are rare. MATERIALS AND METHODS: Retrospective chart review over a 7-year period (Jan 1998-Jan 2005) of PCA treated children dying of cancer was used. RESULTS: Eight children were on PCA for a median duration of 9 days (range, 1 to 50). The daily median intravenous morphine equivalent dose referenced to body weight increased significantly when PCA was initiated and during the last week of life. In the last week of life, the median daily number of delivered and undelivered bolus requests ranged from 7.5-21 and 0-4.5, respectively. To meet children's individual needs, 39 PCA parametre changes on 22 opportunities were performed. Median daily mean pain scores remained low (range, 0-3; numerical rating scale 0-10) throughout the period. CONCLUSION: PCA proved an ideal, dependable and feasible mode of analgesic administration for the individual titration of dose to effect.

[Efficacy of glycopyrronium bromide and scopolamine hydrobromide in patients with death rattle: a randomized controlled study]. / Die Wirkung von Glycopyrroniumbromid im Vergleich mit Scopolamin-Hydrobromicum beim terminalen Rasseln: Eine randomisierte, doppelblinde Pilotstudie.

BACKGROUND: Death rattle is an extremely distressing symptom for the dying patient and for his environment. The aim of this study was to assess the efficacy of glycopyrronium bromide as compared with scopolamine hydrobromide in alleviating death rattle in terminal cancer patients with cognitive impairment. METHODS: In a randomized, controlled study design patients were allocated in two groups. Group A received scopolamine hydrobromide in a dose of 0.5 mg intravenously every 6 hours for a period of 12 hours, group B received glycopyrronium bromide 0.4 mg every 6 hours for a period of 12 hours. In addition, standardized sedatives were administered as required and the analgesic therapy continued either orally or, if necessary, subcutaneously or intravenously in equipotent doses. Every 2 hours death rattle was assessed and rated on a scale of 1 to 5 (1 = audible breathing noises, 5 = very severe rattling noises). In addition, restlessness and expressions of pain were assessed and rated on a scale of 1 to 3 (1 = mild, 2 = moderate, 3 = severe). RESULTS: 13 patients were included in the study, 7 patients were allocated to group A and 6 patients to group B. There were no significant differences in demographic data, age, weight and diagnosis distribution between the two groups. Group B demonstrated a significant reduction of death rattle in the first 12 hours (p = 0.029) in comparison to group A. There were no significant differences concerning the side effects (restlessness, expressions of pain) in both groups. CONCLUSION: Glycopyrronium bromide given in a dose of 0,4 mg every six hours demonstrated a significant reduction of death rattle compared to scopolamine hydrobromide. Concerning side effects (restlessness, expressions of pain) there was no difference between both substances.

Transdermal buprenorphine in chronic pain: indications and clinical experience.

Transdermal buprenorphine has been shown to be effective in managing moderate-to-severe cancer pain and severe pain that is unresponsive to nonopioid analgesics. In clinical trials, it provided better pain relief than placebo, despite a higher consumption of rescue analgesia by placebo patients. Analgesia was rated as satisfactory or better by 90% of patients in a long-term follow-up study and 94.6% considered the buprenorphine matrix patch to be user friendly. Transdermal buprenorphine is well tolerated; most adverse events are transient local reactions to the patch or systemic effects typical of treatment with opioids. Even in opioid-experienced volunteers, buprenorphine does not cause respiratory depression at doses up to 70-times higher than those used for analgesia. No problems have been encountered when switching from another opioid to transdermal buprenorphine, or in combining the buprenorphine patch with intravenous morphine or tramadol for breakthrough pain. There is a growing body of evidence that transdermal buprenorphine may be particularly useful for managing neuropathic pain. Most notably, it appears to be effective in treating hyperalgesic states and syndromes characterized by pronounced central sensitization.