Is Preoperative Quantitative Sensory Testing Related to Persistent Postsurgical Pain? A Systematic Literature Review.

Persistent postsurgical pain (PPSP) is a common complication of surgery that significantly affects quality of life. A better understanding of which patients are likely to develop PPSP would help to identify when perioperative and postoperative pain management may require specific attention. Quantitative sensory testing (QST) of a patient's preoperative pain perception is associated with acute postoperative pain, and acute postoperative pain is a risk factor for PPSP. The direct association between preoperative QST and PPSP has not been reviewed to date. In this systematic review, we assessed the relationship of preoperative QST to PPSP. We searched databases with components related to (1) preoperative QST; (2) association testing; and (3) PPSP. Two authors reviewed all titles and abstracts for inclusion. Inclusion criteria were as follows: (1) QST performed before surgery; (2) PPSP assessed ≥3 months postoperatively; and (3) the association between QST measures and PPSP is investigated. The search retrieved 905 articles; 24 studies with 2732 subjects met inclusion criteria. Most studies (22/24) had moderate to high risk of bias in multiple quality domains. Fourteen (58%) studies reported a significant association between preoperative QST and PPSP. Preoperative temporal summation of pain (4 studies), conditioned pain modulation (3 studies), and pressure pain threshold (3 studies) showed the most frequent association with PPSP. The strength of the association between preoperative QST and PPSP varied from weak to strong. Preoperative QST is variably associated with PPSP. Measurements related to central processing of pain may be most consistently associated with PPSP.

Measuring sensory and pain thresholds by Semmes-Weinstein monofilaments in patients with leg ulcers: a pilot study.

OBJECTIVE: Pain is a common and disabling symptom in patients with leg ulcers. Clinical quantification of pain mostly depends on subjective pain reports, which do not reveal underlying mechanisms. The aim of this pilot study is to identify mechanisms underlying the pain in patients with leg ulcers by documenting alterations in pain processing using quantitative sensory testing. METHODS: In nine ulcer patients the mechanical sensory thresholds and the mechanical pain thresholds were determined by Semmes-Weinstein monofilaments (SWM) at three different sites: on the contralateral (unaffected) leg, on the skin of the affected leg 10cm from the ulcer margin, and on the affected leg, close (1-2cm) to the ulcer margin. Besides the mechanical sensory thresholds and mechanical pain thresholds, pain at the site of the ulcer, using an 11-point numeric rating scale (NRS), was documented. RESULTS: Mechanical sensory thresholds were increased in all subjects. Almost half (44%) of patients consistently showed allodynia at the unaffected site. The lowering of mechanical pain thresholds correlated with higher scores on the NRS. CONCLUSION: All patients showed diminished touch and/or protective sensation, which might have contributed to ulcer development via (partial) loss of protective function. The allodynia at the unaffected site suggests the presence of central sensitisation of pain processing.

Avoiding Catch-22: validating the PainDETECT in a in a population of patients with chronic pain.

BACKGROUND: Neuropathic pain is defined as pain caused by a lesion or disease of the somatosensory nervous system and is a major therapeutic challenge. Several screening tools have been developed to help physicians detect patients with neuropathic pain. These have typically been validated in populations pre-stratified for neuropathic pain, leading to a so called "Catch-22 situation:" "a problematic situation for which the only solution is denied by a circumstance inherent in the problem or by a rule". The validity of screening tools needs to be proven in patients with pain who were not pre-stratified on basis of the target outcome: neuropathic pain or non-neuropathic pain. This study aims to assess the validity of the Dutch PainDETECT (PainDETECT-Dlv) in a large population of patients with chronic pain. METHODS: A cross-sectional multicentre design was used to assess PainDETECT-Dlv validity. Included where patients with low back pain radiating into the leg(s), patients with neck-shoulder-arm pain and patients with pain due to a suspected peripheral nerve damage. Patients' pain was classified as having a neuropathic pain component (yes/no) by two experienced physicians ("gold standard"). Physician opinion based on the Grading System was a secondary comparison. RESULTS: In total, 291 patients were included. Primary analysis was done on patients where both physicians agreed upon the pain classification (n = 228). Compared to the physician's classification, PainDETECT-Dlv had a sensitivity of 80% and specificity of 55%, versus the Grading System it achieved 74 and 46%. CONCLUSION: Despite its internal consistency and test-retest reliability the PainDETECT-Dlv is not an effective screening tool for a neuropathic pain component in a population of patients with chronic pain because of its moderate sensitivity and low specificity. Moreover, the indiscriminate use of the PainDETECT-Dlv as a surrogate for clinical assessment should be avoided in daily clinical practice as well as in (clinical-) research. Catch-22 situations in the validation of screening tools can be prevented by not pre-stratifying the patients on basis of the target outcome before inclusion in a validation study for screening instruments. TRIAL REGISTRATION: The protocol was registered prospectively in the Dutch National Trial Register: NTR 3030 .

Tetrahydrocannabinol Does Not Reduce Pain in Patients With Chronic Abdominal Pain in a Phase 2 Placebo-controlled Study.

BACKGROUND & AIMS: Delta-9-tetrahydrocannabinol (THC) is the most abundant cannabinoid from the plant Cannabis sativa. There is only equivocal evidence that THC has analgesic effects. We performed a phase 2 controlled trial to evaluate the analgesic efficacy, pharmacokinetics, safety, and tolerability of an oral tablet containing purified THC in patients with chronic abdominal pain. METHODS: Sixty-five patients with chronic abdominal pain for 3 months or more (numeric rating scale scores of 3 or more) after surgery or because of chronic pancreatitis were randomly assigned to groups given the THC tablet or identical matching placebos for 50-52 days. Subjects in the THC group were given the tablet first in a step-up phase (3 mg 3 times daily for 5 days and then 5 mg 3 times daily for 5 days), followed by a stable dose phase (8 mg 3 times daily until days 50-52). Preceding and during the entire study period, patients were asked to continue taking their medications (including analgesics) according to prescription. Patients reported any additional pain medications in a diary. Efficacy and safety assessments were conducted preceding medication intake (day 1), after 15 days, and at 50-52 days. Plasma samples were collected on study days 1, 15, and 50-52; mean plasma concentration curves of THC and 11-OH-THC were plotted. The primary end point was pain relief, which was measured by a visual analogue scale (VAS) of the mean pain (VAS mean scores) on the basis of information from patient diaries. Secondary end points included pain and quality of life (determined from patient questionnaires), pharmacokinetics, and safety. RESULTS: At days 50-52, VAS mean scores did not differ significantly between the THC and placebo groups (F1,46 = 0.016; P = .901). Between the start and end of the study, VAS mean scores decreased by 1.6 points (40%) in the THC group compared with 1.9 points (37%) in the placebo group. No differences were observed in secondary outcomes. Oral THC was generally well-absorbed. Seven patients in the THC group stopped taking the tablets because of adverse events, compared with 2 patients in the placebo group. All (possibly) related adverse events were mild or moderate. CONCLUSIONS: In a phase 2 study, we found no difference between a THC tablet and a placebo tablet in reducing pain measures in patients with chronic abdominal pain. THC, administered 3 times daily, was safe and well-tolerated during a 50-day to 52-day treatment period. ClinicalTrials.gov number: NCT01562483 and NCT01551511.

Interpersonal Autonomic Physiology: A Systematic Review of the Literature.

Interpersonal autonomic physiology is defined as the relationship between people's physiological dynamics, as indexed by continuous measures of the autonomic nervous system. Findings from this field of study indicate that physiological activity between two or more people can become associated or interdependent, often referred to as physiological synchrony. Physiological synchrony has been found in both new and established relationships across a range of contexts, and it correlates with a number of psychosocial constructs. Given these findings, interpersonal physiological interactions are theorized to be ubiquitous social processes that co-occur with observable behavior. However, this scientific literature is fragmented, making it difficult to evaluate consistency across reports. In an effort to facilitate more standardized scholarly approaches, this systematic review provides a description of existing work in the area and highlights theoretical, methodological, and statistical issues to be addressed in future interpersonal autonomic physiology research.

Single dose delta-9-tetrahydrocannabinol in chronic pancreatitis patients: analgesic efficacy, pharmacokinetics and tolerability.

AIM: We aimed to assess the analgesic efficacy, pharmacokinetics, tolerability and safety of a single dose of Δ9-THC in patients with chronic abdominal pain resulting from chronic pancreatitis (CP). METHODS: This was a randomized, single dose, double-blinded, placebo-controlled, two way crossover study in patients suffering from abdominal pain as result of CP (n = 24), post hoc subdivided into opioid and non-opioid users. Δ9-THC (8 mg) or active placebo (5 mg/10 mg diazepam) was administered orally in a double dummy design. RESULTS: No treatment effect was shown for delta VAS pain scores after Δ9-THC compared with diazepam. Δ9-THC was well absorbed with a mean tmax of 123 min. No significant differences were found between Δ9-THC vs. diazepam for alertness, mood, calmness or balance. Feeling anxious and heart rate were significantly increased after Δ9-THC compared with diazepam. The most frequently reported adverse events (AEs) after Δ9-THC administration were somnolence, dry mouth, dizziness and euphoric mood. CONCLUSIONS: A single dose of Δ9-THC was not efficacious in reducing chronic pain resulting from CP, but was well tolerated with only mild or moderate AEs. The PK results in CP patients showed delayed absorption and an increased variability compared with healthy volunteers.

Psychophysiological Processing of Itch in Patients with Chronic Post-burn Itch: An Exploratory Study.

A substantial proportion of patients with burn injury develop chronic itch, which can severely affect their quality of life. As found in research on chronic pain, different psychophysiological processes may also play a role in chronic itch, of which central sensitization, conditioned modulation, and attentional processes have been studied most frequently. This study aimed to explore psychophysiological processes of chronic post-burn itch by comparing 15 patients with long-term itch due to burn injury with 15 matched healthy controls. Exploratory results indicated tendencies for higher itch sensitivity in patients than in controls, for mechanical stimuli and histamine, but not for electrical stimulation. Results further suggest that the efficacy of itch modulation by an itch- or pain-conditioning stimulus or directing attention towards itch stimuli do not differ between these patients and controls. Further elucidation of the processes underlying post-burn itch may improve the early identification and treatment of burn patients developing chronic itch.

The effect of pregabalin and s-ketamine in total knee arthroplasty patients: A randomized trial.

BACKGROUND AND AIMS: Pain reduction is important for rehabilitation after total knee arthroplasty. Intra- and peri-articular infiltration with local anesthetics may be an alternative to commonly used locoregional techniques. Adding pregabalin orally and s-ketamine intravenously may further reduce postoperative pain. MATERIAL AND METHODS: This prospective, randomized, double-blind, placebo-controlled study compared two methods of perioperative analgesia. Control patients received a standardized multimodal postoperative analgesic regime of paracetamol, diclofenac, and piritramide-patient-controlled analgesia, including ropivacaine knee infiltration during surgery. The study group received pregabalin orally and s-ketamine intravenously as an additional medication to the standard multimodal regimen. The control group received placebo. RESULTS: The study group showed lower piritramide consumption during the first 24 h (P: 0.043), but with more side effects such as diplopia and dizziness. CONCLUSION: Addition of pregabalin and s-ketamine resulted in lower piritramide consumption during the first 24 h postoperatively. However, more investigation on benefits versus side effects of this medication is required.

Pain severity reduces life quality in chronic pancreatitis: Implications for design of future outcome trials.

BACKGROUND/OBJECTIVES: Chronic pancreatitis (CP) is a disabling disease characterised by abdominal pain, and various pancreatic and extra-pancreatic complications. We investigated the interactions between pain characteristics (i.e. pain severity and its pattern in time), complications, and quality of life (QOL) in patients with CP. METHODS: This was a cross-sectional study of 106 patients with CP conducted at two North European tertiary medical centres. Detailed information on clinical patient characteristics was obtained from interviews and through review of the individual patient records. Pain severity scores and pain pattern time profiles were extracted from the modified brief pain inventory short form and correlated to QOL as assessed by the EORTC QLQ-C30 questionnaire. Interactions with exocrine and endocrine pancreatic insufficiency, as well as pancreatic and extra-pancreatic complications were analysed using regression models. RESULTS: Pain was the most prominent symptom in our cohort and its severity was significantly correlated with EORTC global health status (r = -0.46; P < 0.001) and most functional and symptom subscales. In contrast the patterns of pain in time were not associated with any of the life quality subscales. When controlling for interactions from exocrine and endocrine pancreatic insufficiency no effect modifications were evident (P = 0.72 and P = 0.85 respectively), while the presence of pancreatic and extra-pancreatic complications was associated with an almost 15% decrease in life quality (P = 0.004). CONCLUSIONS: Pain severity and disease related complications significantly reduce life quality in patients with CP. This information is important in order to design more accurate and clinical meaningful endpoints in future outcome trials.

Detecting the neuropathic pain component in the clinical setting: a study protocol for validation of screening instruments for the presence of a neuropathic pain component.

BACKGROUND: The presence of nerve damage plays a key role in the development and prognosis of chronic pain states. Assessment of the presence and severity of a neuropathic pain component (NePC) is key in diagnosing chronic pain patients. Low back pain (LBP) and neck and shoulder pain (NSP) are highly prevalent and clinically important medical and societal problems in which a NePC is frequently present. The more severe the NePC, the worse the course of the pain, its prognosis and the results of treatment. Reliable and standardised diagnosis of the NePC remains difficult to achieve. Standardized and validated screening tools may help to reliably identify the NePC in individual chronic pain patients. The aim of this study is to validate the Dutch language versions of the PainDETECT Questionnaire (PDQ-Dlv) and the 'Douleur Neuropathique 4 Questions' (DN4-Dlv) for use in primary and specialist medical care settings to screen for a NePC in patients with chronic pain due to (1) LBP, (2) NSP or (3) known peripheral nerve damage (PND). METHODS/DESIGN: The study design is cross-sectional to assess the validity of the PDQ-Dlv and the DN4-Dlv with 2 weeks follow-up for test-retest reliability and 3 months follow-up for monitoring and prognosis. 438 patients with chronic pain due to (1) LBP, (2) NSP or (3) PND. will be included in this study. Based on the IASP definition of neuropathic pain, two physicians will independently assess whether the patient has a NEPC or not. This result will be compared with the outcome of the PDQ-Dlv & DN4-Dlv, the grading system for neuropathic pain, bed side examination and quantitative sensory testing. This study will further collect data regarding prevalence of NePC, general health status, mental health status, functioning, pain attribution and quality of life. DISCUSSION: The rationale for this study is to provide detailed information on the clinimetric quality of the PDQ-Dlv and DN4-Dlv in Dutch speaking countries. Our innovative multi-factorial approach should help achieve more reliable diagnosis and quantification of a NePC in patients with chronic pain. TRIAL REGISTRATION: The Netherlands National Trial Register (NTR3030).

Sensitivity to itch and pain in patients with psoriasis and rheumatoid arthritis.

Symptoms of itch and pain in chronic inflammatory conditions of psoriasis (PS) and rheumatoid arthritis (RA) can highly affect patients' quality of life. Studies in other patient groups indicate that sensitivity to itch and pain is altered in line with the patient's main symptom of either chronic itch or pain, as a result of sensitization processes. This study directly compared whether patients with chronic inflammatory conditions associated with chronic itch or pain display a heightened sensitivity to itch and pain, respectively. Sensitivity to itch and pain was measured by applying stimuli of quantitative sensory testing (QST) in female patients with chronic itch due to PS or chronic pain due to RA. Levels of itch and pain evoked by the QST stimuli as well as the tolerance to the stimuli were determined. Patients with PS reacted to the stimuli with a higher itch response (histamine), while the patients with RA displayed a lowered tolerance to the stimuli (cold pressor test and mechanical stimulation) in comparison with the other patient group. In line with previous studies in other patient groups with chronic itch or pain, further support was found that somatosensory stimuli are processed in line with the patients' main symptom through generic sensitization processes, also in chronic inflammatory conditions such as PS and RA.

Early surgery versus optimal current step-up practice for chronic pancreatitis (ESCAPE): design and rationale of a randomized trial.

BACKGROUND: In current practice, patients with chronic pancreatitis undergo surgical intervention in a late stage of the disease, when conservative treatment and endoscopic interventions have failed. Recent evidence suggests that surgical intervention early on in the disease benefits patients in terms of better pain control and preservation of pancreatic function. Therefore, we designed a randomized controlled trial to evaluate the benefits, risks and costs of early surgical intervention compared to the current stepwise practice for chronic pancreatitis. METHODS/DESIGN: The ESCAPE trial is a randomized controlled, parallel, superiority multicenter trial. Patients with chronic pancreatitis, a dilated pancreatic duct (≥5 mm) and moderate pain and/or frequent flare-ups will be registered and followed monthly as potential candidates for the trial. When a registered patient meets the randomization criteria (i.e. need for opioid analgesics) the patient will be randomized to either early surgical intervention (group A) or optimal current step-up practice (group B). An expert panel of chronic pancreatitis specialists will oversee the assessment of eligibility and ensure that allocation to either treatment arm is possible. Patients in group A will undergo pancreaticojejunostomy or a Frey-procedure in case of an enlarged pancreatic head (≥4 cm). Patients in group B will undergo a step-up practice of optimal medical treatment, if needed followed by endoscopic interventions, and if needed followed by surgery, according to predefined criteria. Primary outcome is pain assessed with the Izbicki pain score during a follow-up of 18 months. Secondary outcomes include complications, mortality, total direct and indirect costs, quality of life, pancreatic insufficiency, alternative pain scales, length of hospital admission, number of interventions and pancreatitis flare-ups. For the sample size calculation we defined a minimal clinically relevant difference in the primary endpoint as a difference of at least 15 points on the Izbicki pain score during follow-up. To detect this difference a total of 88 patients will be randomized (alpha 0.05, power 90%, drop-out 10%). DISCUSSION: The ESCAPE trial will investigate whether early surgery in chronic pancreatitis is beneficial in terms of pain relief, pancreatic function and quality of life, compared with current step-up practice. TRIAL REGISTRATION: ISRCTN: ISRCTN45877994.

Patients with persistent pain after breast cancer treatment show enhanced alpha activity in spontaneous EEG.

OBJECTIVE: The aim of the present study was to investigate whether patients with persistent pain after breast cancer treatment show an enhanced and slowed dominant alpha activity in their electroencephalogram (EEG) recorded during rest in comparison with patients that also had undergone breast cancer treatment but do not have pain. METHODS: The spontaneous EEG was recorded during rest and before painful stimulation of the calf and analyzed with spectral analysis (Fast Fourier Transformation). Outcome measures, i.e., alpha indices (center of gravity and overall amplitude), were statistically tested between patients with and without persistent pain. RESULTS: In comparison with patients without pain, patients with persistent pain after breast cancer treatment show more alpha activity in their spontaneous EEG observed from parietal-occipital brain regions. CONCLUSION: Persistent pain after breast cancer treatment affects spontaneous brain activity, which might influence cognitive functioning.

Cross-cultural adaptation to the Dutch language of the PainDETECT-Questionnaire.

BACKGROUND: The PainDETECT-Questionnaire (PDQ) helps to identify neuropathic components in patients suffering from pain. It can be used by clinicians in daily practice and in clinical trials. AIM: The aim of this study is to perform a translation and cross-cultural adaptation of the PDQ for use in the Netherlands and Belgium. METHODS: The first phase was to translate and cross-culturally adapt the PDQ to Dutch. The second phase was to assess the face validity in the Netherlands and Belgium using qualitative and quantitative data collection. RESULTS: The length, the readability, and the clarity of the questionnaire were good for all patients. The questionnaire was judged to have a good layout and to be clearly organized. CONCLUSION: The PDQ Dutch language Version is a well translated and cross-culturally adapted questionnaire, which might be useful for screening for neuropathic components of pain in the Netherlands and Belgium.

The effect of high-frequency conditioning stimulation of human skin on reported pain intensity and event-related potentials.

High-frequency conditioning electrical stimulation (HFS) of human skin induces an increased pain sensitivity to mechanical stimuli in the surrounding nonconditioned skin. The aim of this study was to investigate the effect of HFS on reported pain sensitivity to single electrical stimuli applied within the area of conditioning stimulation. We also investigated the central nervous system responsiveness to these electrical stimuli by measuring event-related potentials (ERPs). Single electrical test stimuli were applied in the conditioned area before and 30 min after HFS. During electrical test stimulation, the reported pain intensity (numerical rating scale) and EEG (ERPs) were measured. Thirty minutes after conditioning stimulation, we observed a decrease of reported pain intensity at both the conditioned and control (opposite arm) skin site in response to the single electrical test stimuli. In contrast, we observed enhanced ERP amplitudes after HFS at the conditioned skin site, compared with control site, in response to the single electrical test stimuli. Recently, it has been proposed that ERPs, at least partly, reflect a saliency detection system. Therefore, the enhanced ERPs might reflect enhanced saliency to potentially threatening stimuli.

Pregabalin reduces pain in patients with chronic pancreatitis in a randomized, controlled trial.

BACKGROUND & AIMS: Pain is a disabling symptom for patients with chronic pancreatitis (CP) and difficult to treat. Evidence from basic science and human studies indicates that pain processing by the central nervous system is abnormal and resembles that observed in patients with neuropathic pain disorders. We investigated whether agents used to treat patients with neuropathic pain are effective in CP. METHODS: We conducted a randomized, double-blind, placebo-controlled trial to evaluate the effects of the gabapentoid pregabalin as an adjuvant analgesic. We measured pain relief, health status, quality of life, and tolerability in 64 patients with pain from CP; they were randomly assigned to groups given increasing doses of pregabalin or placebo (control) for 3 consecutive weeks. The primary end point was pain relief, based on a visual analogue scale documented by a pain diary. Secondary end points included Patients' Global Impression of Change (PGIC) score, changes in physical and functional scales, pain character, quality of life, and tolerability. RESULTS: Pregabalin, compared with placebo, caused more effective pain relief after 3 weeks of treatment (36% vs 24%; mean difference, 12%; 95% confidence interval, 22%-2%; P = .02). The percentage of patients with much or very much improved health status (PGIC score) at the end of the study was higher in the pregabalin than the control group (44% vs 21%; P = .048). Changes in physical and functional scales, pain character, quality of life, and number of serious adverse events were comparable between groups. CONCLUSIONS: In a placebo-controlled trial, pregabalin is an effective adjuvant therapy for pain in patients with CP.

Reduced cortical thickness of brain areas involved in pain processing in patients with chronic pancreatitis.

BACKGROUND & AIMS: Patients with painful chronic pancreatitis (CP) might have abnormal brain function. We assessed cortical thickness in brain areas involved in visceral pain processing. METHODS: We analyzed brain morphologies of 19 patients with painful CP and compared them with 15 healthy individuals (controls) by using a 3T magnetic resonance scanner. By using an automated method with surface-based cortical segmentation, we assessed cortical thickness of the primary (SI) and secondary (SII) somatosensory cortex; prefrontal cortex (PFC); frontal cortex (FC); anterior (ACC), mid (MCC), and posterior (PCC) cingulate cortex; and insula. The occipital middle sulcus was used as a control area. The pain score was determined on the basis of the average daily amount of pain during 1 week. RESULTS: Compared with controls, patients with CP had reduced overall cortical thickness (P = .0012), without effects of modification for diabetes, alcoholic etiologies, or opioid treatment (all P values >.05). In patients with CP, the cortical thickness was decreased in SII (P = .002, compared with controls), PFC (P = .046), FC (P = .0003), MCC (P = .001), and insula (P = .002). There were no differences in cortical thickness between CP patients and controls in the control area (P = .20), SI (P = .06), ACC (P = .95), or PCC (P = .42). Cortical thickness in the affected areas correlated with pain score (r = 0.47, P = .003). CONCLUSIONS: In patients with CP, brain areas involved in pain processing have reduced cortical thickness. As a result of long-term, ongoing pain input to the neuromatrix, cortical thickness might serve as a measure for overall pain system dysfunction, as observed in other diseases characterized by chronic pain.

The analgesic effect of pregabalin in patients with chronic pain is reflected by changes in pharmaco-EEG spectral indices.

AIM: To identify electroencephalographic (EEG) biomarkers for the analgesic effect of pregabalin in patients with chronic visceral pain. METHODS: This was a double-blind, placebo-controlled study in 31 patients suffering from visceral pain due to chronic pancreatitis. Patients received increasing doses of pregabalin (75mg-300mg twice a day) or matching placebo during 3 weeks of treatment. Pain scores were documented in a diary based on a visual analogue scale. In addition, brief pain inventory-short form (BPI) and quality of life questionnaires were collected prior to and after the study period. Multi-channel resting EEG was recorded before treatment onset and at the end of the study. Changes in EEG spectral indices were extracted, and individual changes were classified by a support vector machine (SVM) to discriminate the pregabalin and placebo responses. Changes in individual spectral indices and pain scores were correlated. RESULTS: Pregabalin increased normalized intensity in low spectral indices, most prominent in the theta band (3.5-7.5Hz), difference of -3.18, 95% CI -3.57, -2.80; P= 0.03. No changes in spectral indices were seen for placebo. The maximum difference between pregabalin and placebo treated patients was seen in the parietal region, with a classification accuracy of 85.7% (P= 0.009). Individual changes in EEG indices were correlated with changes in pain diary (P= 0.04) and BPI pain composite scores (P= 0.02). CONCLUSIONS: Changes in spectral indices caused by slowing of brain oscillations were identified as a biomarker for the central analgesic effect of pregabalin. The developed methodology may provide perspectives to assess individual responses to treatment in personalized medicine.

The long-term outcome of transcutaneous electrical nerve stimulation in the treatment for patients with chronic pain: a randomized, placebo-controlled trial.

BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) is an easy to use analgesic intervention. However, long-term randomized placebo-controlled studies with treatment periods of more than 3 months have not been executed to date. The aim of our study is to explore the long-term (1 year) time course of the treatment effects of TENS compared to placebo (sham TENS). METHOD: We performed a randomized placebo-controlled trial in patients with chronic pain (165), referred to a multidisciplinary pain center of a university hospital. Main outcome measures are the proportion of patients satisfied with treatment result and willing to continue treatment, pain intensity, pain disability, and perceived health status. RESULTS: Survival analysis of time courses of proportions of satisfied patients revealed no significant differences (P = 0.79; log-rank test) for TENS treatment compared to sham TENS. After 1 year, 30% (24/81) of the patients of the TENS group and 23% (19/82) of the sham TENS group were satisfied with treatment result. These patients experienced a mean overall improvement of 62.7% (n = 43). This effect was not significantly different between both groups. For satisfied patients, there were no differences in pain intensity or disability and perceived health status between the TENS and sham TENS group. CONCLUSIONS: Transcutaneous electrical nerve stimulation and sham TENS show similar effects in patients with chronic pain over a period of 1 year. We found support for a long sustained placebo effect.