Using screening tools to identify neuropathic pain.
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Health Status Indicators↗
Biomedical subjects
Rainer Freynhagen
Publications and source records attributed to Rainer Freynhagen.
painDETECT: a new screening questionnaire to identify neuropathic components in patients with back pain.
OBJECTIVE: Nociceptive and neuropathic components both contribute to pain. Since these components require different pain management strategies, correct pain diagnosis before and during treatment is highly desirable. As low back pain (LBP) patients constitute an important subgroup of chronic pain patients, we addressed the following issues: (i) to establish a simple, validated screening tool to detect neuropathic pain (NeP) components in chronic LBP patients, (ii) to determine the prevalence of neuropathic pain components in LBP in a large-scale survey, and (iii) to determine whether LBP patients with an NeP component suffer from worse, or different, co-morbidities. METHODS: In co-operation with the German Research Network on Neuropathic Pain we developed and validated the painDETECT questionnaire (PD-Q) in a prospective, multicentre study and subsequently applied it to approximately 8000 LBP patients. RESULTS: The PD-Q is a reliable screening tool with high sensitivity, specificity and positive predictive accuracy; these were 84% in a palm-top computerised version and 85%, 80% and 83%, respectively, in a corresponding pencil-and-paper questionnaire. In an unselected cohort of chronic LBP patients, 37% were found to have predominantly neuropathic pain. Patients with NeP showed higher ratings of pain intensity, with more (and more severe) co-morbidities such as depression, panic/anxiety and sleep disorders. This also affected functionality and use of health-care resources. On the basis of given prevalence of LBP in the general population, we calculated that 14.5% of all female and 11.4% of all male Germans suffer from LBP with a predominant neuropathic pain component. CONCLUSION: Simple, patient-based, easy-to-use screening questionnaires can determine the prevalence of neuropathic pain components both in individual LBP patients and in heterogeneous cohorts of such patients. Since NeP correlates with more intense pain, more severe co-morbidity and poorer quality of life, accurate diagnosis is a milestone in choosing appropriate therapy.
Adult↗
Screening of neuropathic pain components in patients with chronic back pain associated with nerve root compression: a prospective observational pilot study (MIPORT).
OBJECTIVE: Chronic back pain is characterized by a combination of neuropathic and nociceptive mechanisms of pain generation. The prevalence of the neuropathic pain component is unknown. Thus, in the context of an explorative study, we aimed to determine the prevalence of signs and symptoms indicating neuropathic pain in adult patients treated by orthopaedists. We also aimed to assess the usefulness of handheld computers (PDAs) in data collection. METHODS: Prospective epidemiological study in 18 orthopaedic practices or centres throughout Germany. Physician and patient questionnaires (paper/pencil or on handheld computers, PDAs) for patients with back pain of at least 3 months in duration were applied, as well as the von Korff score to assess pain intensity (visual analogue scale, VAS; 0 = no pain, 10 = worst possible pain) and pain characteristics, the Hannover Functional Ability Questionnaire (FFbH-R), and if patients agreed to provide information, the short-form Patient Health Questionnaire (PHQ-D) for depression. RESULTS: For 717 patients, both patient and physician questionnaires were available. Mean patient age was 56 years; pain was predominantly located in the low back (87%). Median current pain intensity on the VAS was 5.0. Confirmed key signs and symptoms indicated neuropathic pain was frequent, e.g. radicular pain radiating beyond the knee towards the foot (40.0%), positive Lasegue sign (18.4%), or absent patellar reflex (17.3%). A third of all patients (33.5%) had >or=3 characteristic signs for neuropathic pain. Patient functionality was severely reduced (median 43.3%). There were no relevant differences in outcomes between patients using the paper/pencil method (47%) versus those preferring PDAs (53%). CONCLUSION: Screening for neuropathic pain in this setting is feasible with simple questionnaires and scales on PDAs. Neuropathic pain is a major contributor to chronic back pain and a frequent component in patients seen by orthopaedists. At least one third of all patients should undergo additional diagnostic measures to confirm the cause of neuropathic pain.
Back Pain↗
Imaging pain modulation by subanesthetic S-(+)-ketamine.
Little is known about the effects of low-dose S-(+)-ketamine on the cerebral processing of pain. We investigated the effects of subanesthetic IV S-(+)-ketamine doses on the perception of experimental painful heat stimuli. Healthy volunteers were evaluated with functional magnetic resonance imaging (fMRI) while receiving the painful stimuli in conjunction with placebo and increasing doses (0.05, 0.1, 0.15 mg x kg(-1) x h(-1)) of ketamine infusion. Vital variables were monitored and all subjects rated pain intensity and unpleasantness on a numerical rating scale. Alterations in consciousness were measured using a psycho-behavioral questionnaire. Pain unpleasantness declined as ketamine dosage was increased (55.1% decrease, placebo versus 0.15 mg x kg(-1) x h(-1) ketamine). Pain intensity ratings also decreased with increasing ketamine dosage but to a lesser extent (23.1% decrease). During placebo administration, a typical pain activation network (thalamus, insula, cingulate, and prefrontal cortex) was found, whereas decreased pain perception with ketamine was associated with a dose-dependent reduction of pain-induced cerebral activations. Analysis of the dose-dependent ketamine effects on pain processing showed a decreasing activation of the secondary somatosensory cortex (S2), insula and anterior cingulate cortex. This part of the anterior cingulate cortex (midcingulate cortex) has been linked with the affective pain component that underlines the potency of ketamine in modulating affective pain processing.
Adult↗
Fatal respiratory depression after multiple intravenous morphine injections.
A 26-year-old female was treated with morphine within the first 2 hours after knee surgery, in an attempt to titrate analgesia. The patient received a total of four intravenous injections of morphine 35 mg in total. Soon after the last injection the patient had adequate pain relief, was in a good clinical state and had adequate blood oxygenation. However, 40 minutes later, the patient had a deep respiratory depression followed by a fatal cardiac arrest. Solving the case in a medico-legal context was possible by applying results of clinical pharmacokinetic research on opioid analgesics, most importantly morphine, to this particular clinical case. This knowledge made it possible to estimate the probable concentrations of morphine at the site of its effect, the brain, during the time of the fatal event, and to show that these concentrations could have produced respiratory depression. We mainly attribute the fatal intoxication of morphine to the lag period needed for the transfer of morphine across the blood-brain barrier. Because of its slow transfer between plasma and the effect site, the CNS effects of morphine are delayed from its plasma concentrations to a clinically relevant degree. Successive injections at short intervals of relatively high amounts of morphine increase the clinical relevance of this delay. The present report demonstrates an important application of clinical pharmacokinetics for explaining clinical observations at a scientific level and transferring theoretical knowledge from clinical pharmacokinetics into daily clinical practice as a basis for rational opioid selection.
Adult↗
Mirtazapine and its enantiomers differentially modulate acute thermal nociception in rats.
The antidepressant mirtazapine is an optically active drug and currently marketed as a racemic compound consisting of its S(+) and R(-)-enantiomers in a 50:50 mixture. As stereochemistry of antidepressants has become increasingly important to consider for the relevance of their analgesic properties, we investigated the effect of (+/-)-mirtazapine and its enantiomers in an animal model of acute thermal nociception. Wistar rats were injected intrathecal with either (+/-)-mirtazapine, R(-)-mirtazapine, S(+)-mirtazapine from 1 to 0.001 mg/kg and vehicle (0.9% NaCl), respectively. The effects on thermal paw withdrawal thresholds were monitored using the Hargreaves test. (+/-)-Mirtazapine exerted pro- and antinociceptive effects in acute thermal nociception, whereas R(-)-mirtazapine showed solely antinociceptive and S(+)-mirtazapine pronociceptive properties. These results clearly demonstrate a differential effect of (+/-)-mirtazapine and its enantiomers on nociception. As R(-)-mirtazapine exerts the antinociceptive activity of the racemic mixture it may be a putative candidate for an enantioselective use as analgesic.
Afferent Pathways↗
Efficacy of pregabalin in neuropathic pain evaluated in a 12-week, randomised, double-blind, multicentre, placebo-controlled trial of flexible- and fixed-dose regimens.
Pregabalin binds with high affinity to the alpha2-delta subunit protein of voltage-gated calcium channels and, thereby, reduces release of excitatory neurotransmitters. This 12-week randomised, double-blind, multicentre, placebo-controlled, parallel-group study evaluated the efficacy and safety of pregabalin in patients with chronic postherpetic neuralgia (PHN) or painful diabetic peripheral neuropathy (DPN). Patients were randomised to placebo (n=65) or to one of two pregabalin regimens: a flexible schedule of 150, 300, 450, and 600 mg/day with weekly dose escalation based on patients' individual responses and tolerability (n=141) or a fixed schedule of 300 mg/day for 1 week followed by 600 mg/day for 11 weeks (n=132). Both flexible- and fixed-dose pregabalin significantly reduced endpoint mean pain score (primary outcome) versus placebo (P=0.002, P<0.001) and were significantly superior to placebo in improving pain-related sleep interference (P<0.001). The most common adverse events (AEs) for pregabalin-treated patients were dizziness, peripheral oedema, weight gain (not affecting diabetes control), and somnolence. These results are consistent with previous studies' demonstrating pregabalin's efficacy, tolerability, and safety for treatment of chronic neuropathic pain associated with DPN or PHN. Pregabalin dosing aimed at optimal balance of efficacy and tolerability provides significant pain relief and may reduce risks for AEs and therapy discontinuation.
Adult↗
Switching from reservoir to matrix systems for the transdermal delivery of fentanyl: a prospective, multicenter pilot study in outpatients with chronic pain.
Matrix systems for transdermal fentanyl will replace the reservoir systems in Europe. In an industry-independent, prospective, multicenter pilot study, 46 outpatients with chronic pain were asked to assess pain intensity, sleep interference, adverse events, and multiple secondary parameters during administration of the last reservoir and the first two matrix patches. There was no difference in pain intensity, sleep interference, and the rate of adverse events between both systems. Self assessment on a 6-step numeric rating scale (1 = very good, 6 = insufficient) comparing the two systems (reservoir vs. matrix) showed that skin compatibility (2.6 vs. 1.5), adhesive properties (3.2 vs. 1.8), wearability/comfort (2.8 vs. 1.5), and general satisfaction (2.5 vs. 1.8) improved significantly with the new matrix technology. At study endpoint, 91% of patients preferred the matrix system for future use. The new fentanyl matrix system is characterized by a high level of general satisfaction, ease of use, patient acceptance, and improved skin compatibility. Reservoir and matrix systems appear to have comparable efficacy and safety so that outpatients can be switched directly from the reservoir to the matrix system without difficulties and new dose titration.
Administration, Cutaneous↗
Increase in skin temperature after spinal anesthesia in infants.
BACKGROUND AND OBJECTIVES: The relatively stable hemodynamics during spinal anesthesia in infants have been attributed to a less active sympathetic nervous system in comparison with adults. Thus, the authors evaluated sympathetic block primarily by measurement of skin temperature and secondarily by determination of noninvasive blood pressure as an indirect sign of sympatholysis. METHODS: In 15 infants (postconceptual age: 45.0 +/- 4.8 weeks; weight: 4.0 +/- 1.2 kg) scheduled for repair of inguinal hernia under spinal anesthesia, skin temperature at the T4 level and at the plantar foot was measured before and after spinal anesthesia. Spinal anesthesia was induced at the L4/L5 interspace with 0.5% hyperbaric bupivacaine 1 mg/kg with 10 microg/kg adrenaline added. RESULTS: Temperature at the plantar foot after spinal anesthesia rose significantly from 33.0 degrees C +/- 1.3 degrees C to 34.7 degrees C +/- 1.4 degrees C within 10 minutes and to 35.6 degrees C +/- 0.9 degrees C after 20 minutes (P < .0001), whereas the temperature at the thorax remained constant at 35 degrees C to 36 degrees C. Systolic and diastolic blood pressure decreased by 15.9 +/- 11.4 mm Hg and 9.0 +/- 9.2 mm Hg, respectively (P < .01), but remained within normal range in all cases. CONCLUSIONS: The authors found a significant increase in skin temperature of the feet within 10 minutes as a sign of sympatholysis, whereas trunk temperature remained constant. Blood pressure decreased but remained within the normal range, despite the observed sympatholysis.
Anesthesia, Spinal↗
Uniform distribution of skin-temperature increase after different regional-anesthesia techniques of the lower extremity.
BACKGROUND AND OBJECTIVES: Skin-temperature increase is a reliable but late indicator of success during regional-anesthesia techniques. The goal of this study is to determine the distribution of skin-temperature changes during different regional techniques. Does skin temperature increase in the whole area innervated by the blocked neural structures or only in certain regions within this area with the capability to react preferentially to sympathetic block (i.e., vessel-rich skin)? Although onset time may vary between different regional-anesthetic techniques, we hypothesized that the distribution of skin warming is equal. METHODS: Skin temperature was assessed continuously by infrared thermography in 24 patients who received either combined femoral-nerve and sciatic-nerve block, epidural anesthesia, or spinal anesthesia. RESULTS: Apart from differences in time of onset, no differential spatial distribution of skin-temperature changes could be detected. The earliest and greatest rise of skin temperature occurred at the great toe (10.6 degrees C +/- 0.4 degrees C), became smaller proximally, and was negligible above the ankles, irrespective of the type and extent of block. Video-thermography revealed that cold blood flows through subcutaneous veins immediately after onset of sympathetic block and initially decreases skin temperature (0.6 degrees C +/- 0.3 degrees C) during onset of spinal anesthesia. CONCLUSION: Irrespective of the applied regional-anesthetic technique, skin-temperature changes are more pronounced distally. Thermography prevents false measurements of skin temperature above subcutaneous veins and displays flow of cold blood as the mechanism of initial skin-temperature drop after regional anesthesia. Measurements of skin-temperature increase cannot be used to evaluate the extent of analgesia or sympathetic block.
Adult↗