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.

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.

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.

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.

Altered brain microstructure assessed by diffusion tensor imaging in patients with chronic pancreatitis.

OBJECTIVE: In patients with painful chronic pancreatitis (CP) there is increasing evidence of abnormal pain processing in the central nervous system. Using magnetic resonance (MR) diffusion tensor imaging, brain microstructure in areas involved in processing of visceral pain was characterised and these findings were correlated to clinical pain scores. METHODS: 23 patients with CP pain and 14 controls were studied in a 3T MR scanner. Apparent diffusion coefficient (ADC) (ie, diffusivity of water) and fractional anisotropy (FA) (ie, organisation of fibres) values were assessed in the amygdala, cingulate cortex, insula, prefrontal cortex and secondary sensory cortex. Daily pain scores and the Brief Pain Inventory Short Form were collected 1 week before the investigation. RESULTS: In grey matter, patients had increased ADC values in amygdala, cingulate cortex, insula and prefrontal cortex, as well as decreased FA values in cingulate cortex and secondary sensory cortex. In white matter, patients had increased ADC values in insula and prefrontal cortex, and decreased FA values in insula and prefrontal cortex (all p values <0.05). An effect modification from the pain pattern (attacks vs continuous pain) was seen in the insula and secondary sensory cortex (p values <0.05), but no effect modifications from diabetes, alcoholic aetiology and opioid treatment were seen (all p values >0.05). Microstructural changes in cingulate and prefrontal cortices were correlated to patients' clinical pain scores. CONCLUSION: The findings suggest that microstructural changes of the brain accompany pain in CP. The changes are likely to be a consequence of ongoing pain and structural reorganisation of the neuromatrix as also seen in other diseases characterised by chronic pain.

Neurophysiological correlates of nociceptive heterosynaptic long-term potentiation in humans.

Long-term potentiation (LTP) is a cellular model of synaptic plasticity and reflects an increase of synaptic strength. LTP is also present in the nociceptive system and is believed to be one of the key mechanisms involved in the manifestations of chronic pain. LTP manifested as an increased response in pain perception can be induced in humans using high-frequency electrical stimulation (HFS). The aim of this study was to induce spinal heterosynaptic LTP using HFS and investigate its heterotopic effects on event-related potentials (ERPs) to repeated nonpainful cutaneous stimuli as a possible electrophysiological cortical correlate of sensitization. Twenty-two healthy subjects were randomly assigned to one of the two experimental conditions: HFS and control stimulation. Before and after the stimulation, both conditions received heterotopic mechanical (pinprick) and paired nonpainful electrical test stimuli to quantify and confirm the effects of HFS on the behavioral level. ERPs to paired nonpainful electrical stimulation were measured simultaneously. Conditioning HFS resulted in significant heterotopic effects after 30 min, including increased perceived intensity in response to (pinprick) mechanical and paired nonpainful electrical stimulation compared with control. The paired nonpainful electrical stimuli were accompanied by significantly enhanced responses regarding the ERP N1-P2 peak-to-peak and P300 amplitude compared with control. These findings suggest that HFS is capable of producing heterosynaptic spinal LTP that can be measured not only behaviorally but also using ERPs.

Qualitative and Quantitative Aspects of Pain in Patients With Myotonic Dystrophy Type 2.

Pain is a common but often ignored symptom in patients with myotonic dystrophy type 2 (DM2). In this explorative study, we assessed qualitative and quantitative aspects of pain in DM2 using 4 questionnaires and quantitative sensory testing. A disease control group (fibromyalgia [FMS]) as well as healthy controls were used to compare the results, because pain in DM2 shows many clinical similarities to pain in FMS. Thirty-four patients with genetically confirmed DM2 (71% female, mean age 54 years), 28 patients with FMS, and 33 healthy controls were included, age- as well as sex-matched. Pain prevalence was 65% in DM2, 100% in FMS (P < .001), and 15% in healthy controls (P < .001). The mean of the pressure pain thresholds was lower in DM2 than in healthy controls (P = .016), with the largest differences in the rectus femoris, trapezius, and thenar muscles. Mechanical and electric pain thresholds were significantly higher in DM2 than in FMS, and no differences were found in electric pain thresholds between DM2 and healthy controls. These results confirm that pain is a frequent and important symptom in patients with DM2, affecting quality of life. Peripheral mechanisms of pain seem to play a role in DM2. The widespreadness of the hyperalgesia suggests central sensitization, but this finding was not supported by the other results. This study opens new avenues for further research and eventually novel treatment strategies, in DM2 as well as in other muscular disorders. PERSPECTIVE: This article presents qualitative as well as quantitative aspects of pain in patients with DM2. Pain is a frequent and important symptom in patients with DM2, affecting quality of life. We found mechanical hyperalgesia, indicative of a peripheral mechanism of pain. The widespreadness of hyperalgesia may suggest central sensitization, but this finding was not supported by other results and needs further exploration.

The role of angina pectoris in chronic pain after coronary artery bypass graft surgery.

UNLABELLED: Visceral nociception readily sensitizes the central nervous system, causing referred somatic pain and hyperalgesia via somato-visceral convergence. Hyperalgesia in the perioperative period may increase vulnerability to subsequent development of chronic pain. The study aim is to investigate the role of angina pectoris, an ischemic visceral pain, in long-term pain after coronary artery bypass surgery (CABG). We sent questionnaires to 369 patients who underwent CABG surgery in 2003. Questions were asked about angina pectoris and other pain in the period before surgery, the first week postoperatively (= acute pain), and the period after 3 months after surgery (= chronic pain). We obtained results from 256 patients (response rate = 69%). The point prevalence of chronic pain after CABG was 27% after a mean follow-up of 16 months (SD +/- 3 months). Patients with chronic pain after CABG had more angina pectoris than those without chronic pain: Before surgery (P = .07), early on postoperatively (P = .004), and more than 3 months after surgery (P = .000004). We found cumulative prevalences of chronic pain after CABG at 3 months of 39%, and of 32% after 6 months. Other predictive factors for chronic pain after CABG were acute postoperative pain (P = .00002) and younger age (P = .002). Angina pectoris is associated with chronic pain after CABG surgery. Other predictive factors include acute postoperative pain and younger age. PERSPECTIVE: The influence of postoperative angina pectoris for chronic pain after CABG surgery has not been described in the literature to date. Visceral nociception may play an important role in the development of chronic pain after surgery and should be taken into account in future studies.

Investigating the validity of the DN4 in a consecutive population of patients with chronic pain.

Neuropathic pain is clinically described as pain caused by a lesion or disease of the somatosensory nervous system. The aim of this study was to assess the validity of the Dutch version of the DN4, in a cross-sectional multicentre design, as a screening tool for detecting a neuropathic pain component in a large consecutive, not pre-stratified on basis of the target outcome, population of patients with chronic pain. Patients' pain was classified by two independent (pain-)physicians as the gold standard. The analysis was initially performed on the outcomes of those patients (n = 228 out of 291) in whom both physicians agreed in their pain classification. Compared to the gold standard the DN4 had a sensitivity of 75% and specificity of 76%. The DN4-symptoms (seven interview items) solely resulted in a sensitivity of 70% and a specificity of 67%. For the DN4-signs (three examination items) it was respectively 75% and 75%. In conclusion, because it seems that the DN4 helps to identify a neuropathic pain component in a consecutive population of patients with chronic pain in a moderate way, a comprehensive (physical-) examination by the physician is still obligate.

Impairments as measured by ISS do not greatly change between one and eight years after CRPS 1 diagnosis.

BACKGROUND: Complex Regional Pain Syndrome type 1 (CRPS 1) is a potentially incapacitating complication in which pain seems to be the most disabling factor. We performed a late follow up study of a well-defined CRPS 1 population more than eight years after diagnosis. The relationships between early and late impairments were studied with a view to outcome prediction and to investigate possible differences in long-term impairments according to initial CRPS 1 subdiagnosis (i.e. "warm" or "cold", diagnosed according to skin temperature measured via infrared thermometer). METHODS: We again measured patients using the Impairment Level SumScore (ISS) (T8). These data were compared with earlier ISS measurements at CRPS diagnosis (T0) and after one year's treatment (T1). Correlations were determined between these measures. RESULTS: Forty-five patients participated in the present study. Total median ISS improved by 55% (statistically/clinically significant) after one year's treatment (T1), and worsened (non-significantly) by 14% from T1 to T8 - without differences according to original subdiagnosis. ISS correlations were stronger for T1 vs. T8 than for T0 vs. T1 or T0 vs. T8, being strongest for the ISS factors related to pain. CONCLUSIONS: Considerable impairments, as measured by ISS, are still present over eight years after first CRPS 1 diagnosis. These do not greatly change between one and eight years post-diagnosis. ISS outcomes are similar for "cold" and "warm" CRPS 1 diagnostic subgroups. Component ISS scores associated with pain appear to possess greatest predictive power.

Chronic pancreatitis patients show hyperalgesia of central origin: a pilot study.

BACKGROUND: The pain of chronic pancreatitis remains challenging to manage, with treatment all too often being unsuccessful. A main reason for this is lacking understanding of underlying mechanisms of chronic pain in these patients. AIM: To document, using somatic quantitative sensory testing, changes in central nervous system processing (neuroplasticity) associated with chronic pancreatitis pain and thus gain insight into underlying pain mechanisms. PATIENTS AND METHODS: We studied 10 chronic pancreatitis patients on stable opioid analgesic medication. Ten matched surgical patients without pain served as controls. Pain verbal numeric rating scores (NRS) and thresholds to electric skin stimulation and pressure pain were measured in dermatomes T10 (pancreatic area), C5, T4, L1 and L4. RESULTS: The pancreatitis patients had a median NRS pain score of 5 (range 3-8). Electric sensation and pain thresholds were significantly increased in the pancreatic region, tending to be more so in female pancreatitis patients. Pressure pain thresholds were significantly lower in pancreatitis patients than in controls, with men tending towards greater generalised relative hyperalgesia than women. CONCLUSIONS: Chronic pancreatitis patients show pronounced generalised deep hyperalgesia that is present despite opioid therapy. These signs, consistent with central sensitisation, appear relatively more prominent in men than women. There is also evidence suggesting that women may have a better segmental inhibitory response than men, possibly explaining their relatively less prominent generalised deep tissue hyperalgesia compared to men.

Is Timing of Medical Therapy Related to Outcome in Painful Chronic Pancreatitis?

OBJECTIVES: The authors investigated if timing of medical treatment is associated with the analgesic effect of pregabalin or placebo in patients with chronic pancreatitis (CP). METHODS: Sixty-four patients received pregabalin (150-300 mg twice a day) or matching placebo for 3 consecutive weeks. Responders to treatment were defined as patients with a reduction in clinical pain scores of 30% or greater. Factors associated with timing of pain treatment (ie, duration of CP and opioid usage) were collected at baseline. In addition, other factors that potentially could influence outcome (eg, clinical pain scores prior to study medication, diabetes, and exocrine pancreatic insufficiency) were also included. Conventional groupwise logistic regression and analysis on the individual patient level with a machine learning technique were used to predict treatment response. RESULTS: In the conventional statistical analysis duration of CP (odds ratio, 0.9; 95% confidence interval, 0.8-1.1; P = 0.3) and opioid treatment (odds ratio, 1.0; 95% confidence interval, 0.9-1.1; P = 0.6) were not associated with pain relief. In addition, none of the supplementary factors were associated with treatment response (all P > 0.1). Likewise, in the individual patient-level analysis, none of the included variables reached classification accuracies greater than chance level (all P > 0.1). CONCLUSIONS: Pregabalin can be added as adjuvant analgesic at any time point during the disease course of CP.

Patients initially diagnosed as 'warm' or 'cold' CRPS 1 show differences in central sensory processing some eight years after diagnosis: a quantitative sensory testing study.

We used quantitative sensory testing (QST) to gain further insight into mechanisms underlying pain in CRPS 1. Specific goals were: (1) to identify altered patterns of sensory processing some 8 years after diagnosis, (2) to document differences in sensory processing between 'warm' and 'cold' diagnostic subgroups, (3) to determine relationships between changed sensory processing and disease progression regarding pain. The study was performed on a cohort of patients (n=47) clinically diagnosed with CRPS 1 of one upper extremity approximately 8 years previously. Pain was quantified by VAS and MacGill Pain Questionnaire (MPQ), and all subjects underwent electrical and mechanical QST. Cold patients (n=13) had poorer MPQ scores than warm ones (n=34), and more pain on electrical stimulation. Their evoked pain increased with disease progression and correlated with clinical pain measures. For both diagnostic subgroups, thresholds to pressure pain were lower on the affected extremity and with disease progression. Eight years after original diagnosis, cold CRPS 1 patients have poorer clinical pain outcomes and show persistent signs of central sensitisation correlating with disease progression. The latter is not the case for warm CRPS 1 patients. Both diagnostic subgroups show greater pressure hyperalgesia on the affected limb and with disease progression. QST may prove useful in the subdiagnosis of CRPS 1 and in quantifying its progression, with both applications warranting further investigation for clinical and research use.

Opioid use in the elderly.

Pain treatment in the elderly is an important challenge to Western societies due to increasing numbers of old persons, their higher incidence of pain, and their greater susceptibility to adverse effects of pain medication. We provide an overview of the factors liable to influence opioid action in the elderly population. A major challenge for the physician prescribing opioids in the elderly is their greater risk of medication-associated problems. Thus, older patients suffer increased vulnerability to adverse drug effects and interactions, higher rates of polypharmacy, and more comorbidity. These problems are compounded by a relative lack of definitive published information. There is clearly a need for more research in this area. Aging affects opioid pharmacokinetics via altered body composition (distribution volumes) and organ function (liver=metabolism, kidney=excretion). Pharmacodynamics is affected via impaired neurotransmitter/peptide production and changed receptor affinities/populations. Older women may need less morphine analgesia postoperatively, while pain sensitivity tends to increase particularly in older men. However, the net effects of changes in opioid pharmacology with age on clinical opioid analgesia remain unclear, probably due to the significantly greater variability in body function with increasing age. Practical recommendations for opioid prescription in the elderly include meticulous review of indication for opioid use, not only initially but also at regular intervals thereafter. A policy of careful titration should be followed, with conservative choice of dosage on starting. Dosing intervals may need to be lengthened subsequently. Finally, it should be remembered that old persons do not necessarily need less opioid than younger ones.