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Biomedical subjects

Flemming W Bach

Publications and source records attributed to Flemming W Bach.

At least 19 recordsLinked to original sources
PubMed2006

Treatment with sumatriptan 50 mg in the mild phase of migraine attacks in patients with infrequent attacks: a randomised, double-blind, placebo-controlled study.

Most migraine patients with infrequent attacks are currently not treated with migrainespecific medication such as triptans. The response of these patients to triptans is unknown. The objective of this study was to investigate the efficacy and tolerability of sumatriptan 50 mg vs. placebo in migraine patents with infrequent migraine attacks when medication is taken during the mild phase of an attack. The study design was double-blind, placebocontrolled, parallel-group and randomised. Migraine patients were recruited by general practitioners and referred to one of 4 study centres. Additional patients were recruited by advertising. The patients were eligible for the study if they had between 6 and 12 migraine attacks with or without aura per year. The patients were instructed to take the medication during the mild phase of a single attack. The primary efficacy measure was the percentage of patients pain-free after 2 h. Fortysix percent of treated attacks were moderate or severe. In the intention-to-treat analysis, sumatriptan was superior (20/51 patients were pain-free) to placebo (8/47 patients pain-free) (p=0.03). Adverse events (AEs) occurred more frequently after sumatriptan (40%) than after placebo (13%) (p=0.003) and most AEs were mild or moderate. In this migraine population with infrequent attacks, sumatriptan was superior to placebo and was generally well tolerated.

Adolescent↗
PubMed2006

Increased muscle pain sensitivity in patients with tension-type headache.

Nociceptive mechanisms in tension-type headache are poorly understood. The aim was to investigate the pain sensitivity of pericranial muscles and a limb muscle in patients with tension-type headache. Experimental muscle pain was induced by standardized infusions of 0.5 ml of 1 M hypertonic saline into two craniofacial muscles (anterior temporalis (TPA) and masseter (MAS)) and a limb muscle (anterior tibial (TA)) in 24 frequent episodic tension-type headache patients (FETTH), 22 chronic tension-type headache patients (CTTH) and 26 age and gender matched healthy subjects. Headache patients were examined twice, both on days with and on days without headache. The pressure pain thresholds (PPTs) were determined before and after infusions. The subjects continuously reported intensity of saline-induced pain on an electronic visual analogue scale (VAS) and the perceived area of pain was drawn on anatomical maps. Headache patients demonstrated significantly lower PPTs, higher saline-evoked VAS pain scores and greater pain areas than healthy subjects at all the tested muscle sites (P<0.05). There was a significant gender difference for the PPTs in all three groups of participants (P<0.05) and for VAS pain scores in the CTTH patients (P<0.05). There was no difference in pain sensitivity between FETTH and CTTH or between patients with or without headache. In conclusion, the present study demonstrates the presence of generalized pain hypersensitivity both in FETTH and CTTH compared to controls which is unrelated to actual headache status and extends to include responses to longer-lasting stimuli which are clinically highly relevant. Gender differences in deep pain sensitivity seem to be a consistent finding both in healthy controls and patients with tension-type headache.

Female↗
PubMed2006

Health-related quality of life and its predictive role for analgesic effect in patients with painful polyneuropathy.

Painful polyneuropathy is a common neuropathic pain condition. The present study describes health-related quality of life (HRQL) in a sample of patients with painful polyneuropathy of different origin and the possible predictive role of HRQL for analgesic effect. Ninety-three patients with a diagnosis of painful polyneuropathy were included in the analysis. Data were obtained from three randomised, placebo-controlled cross-over studies testing the effect of different drugs on polyneuropathic pain (St. John's wort, venlafaxine/imipramine and valproic acid). Patients completed a HRQL questionnaire (SF-36) after a drug-free baseline period and at the end of each treatment period. At baseline, all eight SF-36 scores were lower than in the normal population. No significant differences were found between SF-36 scales during placebo and treatment with valproic acid and St. John's wort. Those two drugs had not shown a pain relieving effect in former analysis. The SF-36 scale of bodily pain (BP) was improved by venlafaxine treatment (p=0.023). General health (GH) and vitality (VT) were improved under treatment with imipramine (GH: p=0.006, VT: p=0.015). In a multivariate logistic regression analysis, baseline SF-36 scores predicted subsequent response to pharmacological treatment. Results show an impaired HRQL in painful polyneuropathy and suggest that HRQL may predict response to analgesic treatment.

Adult↗
PubMed2006

[Neuropathic pain].

Neuropathic pain (NP) occurs secondary to lesions in the nervous system. The definition includes conditions with nervous system dysfunction, which creates problems with diagnostic classification. Lesions may be clinically identified, but signs of dysfunction are less specific. New knowledge of mechanisms behind NP has led to the suggestion that NP should be treated based on mechanisms rather than on diagnosis. However, it is not yet possible to identify mechanisms in individual patients, and present knowledge of drug effects builds on diagnosis. An algorithm for treatment of NP is presented.

Analgesics, Opioid↗
PubMed2006

Differential effect of ketamine and lidocaine on spontaneous and mechanical evoked pain in patients with nerve injury pain.

BACKGROUND: The mechanisms underlying neuropathic pain are incompletely understood. Targeting specific molecular mechanisms in the pain signaling system may assist in understanding key features in neuropathic pains such as allodynia. This study examined the effect of systemically administered ketamine, an N-methyl-D-aspartate receptor antagonist and lidocaine, a sodium channel blocker, on spontaneous pain, brush-evoked pain, and pinprick-evoked pain in patients with nerve injury pain. METHODS: Twenty patients participated in two randomized, double-blinded, placebo-controlled, crossover experiments in which they, on four different days, received a 30-minute intravenous infusion of ketamine (0.24 mg/kg), lidocaine (5 mg/kg), or saline. Ongoing pain, pain evoked by brush and repetitive pinprick stimuli, and acetone was measured before, during, and after infusion. RESULTS: Ketamine significantly reduced ongoing pain and evoked pain to brush and pinprick, whereas lidocaine only reduced evoked pain to repetitive pinprick stimuli. In individual patients, there was no correlation between the pain-relieving effect of lidocaine and ketamine on ongoing or mechanically evoked pains. CONCLUSIONS: N-methyl-D-aspartate receptor-linked systems and sodium channels are involved in generation and maintenance of pain in patients with peripheral nerve injury. It is likely that ongoing pain as well as mechanical hyperalgesia in individual patients is dependent on several separate molecular mechanisms.

Adult↗
PubMed2006

Small-fibre neuropathy in female Fabry patients: reduced allodynia and skin blood flow after topical capsaicin.

Fabry disease is a rare X-linked lysosomal storage disorder. The mutations result in a deficiency of the lysosomal enzyme alpha-galactosidase A causing accumulation of glycosphingolipids in the vascular endothelial cells and many other tissues. Given the X-linked inheritance, male patients are severely affected. Recently, attention has been drawn to female patients whether they also show signs of nerve involvement. An early sign of the disease is painful small-fibre neuropathy. The aim of this study was to evaluate a small-fibre dysfunction in female Fabry patients by using capsaicin applied topically. The response to capsaicin was evaluated by laser Doppler imaging. We found that the female Fabry patients had a significantly smaller increase in blood flow (p = 0.0003) after capsaicin application. The area of static mechanical allodynia and dynamic mechanical hyperalgesia was also significantly smaller (p = 0.006) in female Fabry patients. This indicates that female Fabry patients have a significant loss of small-fibre function and demonstrates that it is possible to evaluate this by a non-invasive method.

Administration, Topical↗
PubMed2005

[Effect of the synthetic cannabinoid dronabinol on central pain in patients with multiple sclerosis--secondary publication].

Cannabinoids reduce allodynia/hyperalgesia in animal pain models, but few clinical studies evaluated the analgesic action in humans. We aimed to evaluate the effect of delta-9-tetrahydrocannabinol (dronabinol) on central pain in MS patients. Twenty-four MS patients participated in a double-blind placebo-controlled crossover trial. Dronabinol reduced the spontaneous pain intensity significantly compared with placebo (4.0 (2.3-6.0) vs. 5.0 (4.0-6.4), median (25th-75th percentiles), p = 0.02). Though dronabinol's analgesic effect is modest, its use should be evaluated considering the general difficulty in treating central pain.

Administration, Oral↗
PubMed2005

Effects of evoked pain on the electromyogram and compound muscle action potential of the brachial biceps muscle.

Muscle pain is often accompanied by a feeling of muscle fatigue and weakness. We examined the effect of experimental muscle pain on the electromyogram (EMG) during maximal voluntary contraction (MVC), and on the compound muscle action potential (CMAP) of the brachial biceps muscle. Twenty-one healthy subjects were injected intramuscularly with 0.1 ml/30 microg of the vanilloid receptor agonist (capsaicin) or 0.2 ml of 5% hypertonic saline. A Teflon-coated cannulated EMG needle was used to record the EMG interference pattern (IP) at MVC. The CMAP of the brachial biceps muscle was obtained by stimulation of the musculocutaneous nerve at the axilla using surface electrodes. Amplitude, mean frequency of the power spectrum, and turns/s of the interference pattern were reduced after pain induced by capsaicin or hypertonic saline. Latency, amplitude, and area-under-curve of the CMAP did not change after injection of either substance. Acute stimulation of muscle nociceptors thus produced a fatiguelike change in the interference pattern during MVC, possibly due to a decrease in motoneuron firing rate and increased muscle fatigability.

Action Potentials↗
PubMed2005

Breakthrough pain in malignant and non-malignant diseases: a review of prevalence, characteristics and mechanisms.

Breakthrough pain or transient worsening of pain in patients with an ongoing steady pain is a well known feature in cancer pain patients, but it is also seen in non-malignant pain conditions with involvement of nerves, muscles, bones or viscera. Continuous and intermittent pain seems to be a general feature of these different pain conditions, and this raises the possibility of one or several common mechanisms underlying breakthrough pain in malignant and non-malignant disorders. Although the mechanisms of spontaneous ongoing pain and intermittent flares of pain (BTP) may be difficult to separate, we suggest that peripheral and/or central sensitization (hyperexcitability) may play a major role in many causes of BTP. Mechanical stimuli (e.g. micro-fractures) changes in chemical environments and release of tumour growth factors may initiate sensitization both peripherally and centrally. It is suggested that sensitization could be the common denominator of BTP in malignant and non-malignant pain.

Humans↗
PubMed2005

Intravenous lidocaine relieves spinal cord injury pain: a randomized controlled trial.

BACKGROUND: Neuropathic pain in spinal cord injury is a common challenging therapeutic condition. The current study examines the analgesic effect of the sodium channel blocker lidocaine on neuropathic pain in patients with spinal cord injury and the predictive role of concomitant evoked pain on pain relief with lidocaine. METHODS: Twenty-four spinal cord injury patients with neuropathic pain at or below the level of injury were randomized and completed a double-blind crossover trial of 5 mg/kg lidocaine and placebo infused over 30 min. Twelve patients reported evoked pain, and 12 patients had no evoked pain. Spontaneous and evoked pains were assessed using a visual analog scale and quantitative sensory testing. RESULTS: Lidocaine significantly reduced spontaneous pain in all patients (P < 0.01) and in each of the two groups with (P < 0.01) and without (P = 0.048) evoked pain, with no difference in number of responders (pain reduction > or = 33%) between the patients with (n = 6) and without (n = 5) evoked pain. Lidocaine significantly relieved both at-level and below-level neuropathic pain and decreased brush-evoked dysesthesia but not cold allodynia, pinprick hyperalgesia, or pain evoked by repetitive pinprick. CONCLUSIONS: Lidocaine reduced neuropathic pain at and below the level of injury irrespective of the presence or absence of evoked pain. Results are consistent with a central-acting effect of sodium channel blockers acting on neuronal hyperexcitability. Agents (such as anticonvulsants or antiarrhythmics) with sodium channel-blocking properties may be a treatment option for spinal cord injury pain.

Adult↗
PubMed2004

Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double blind placebo controlled crossover trial.

OBJECTIVE: To evaluate the effect of the oral synthetic delta-9-tetrahydrocannabinol dronabinol on central neuropathic pain in patients with multiple sclerosis. DESIGN: Randomised double blind placebo controlled crossover trial. SETTING: Outpatient clinic, University Hospital of Aarhus, Denmark. PARTICIPANTS: 24 patients aged between 23 and 55 years with multiple sclerosis and central pain. INTERVENTION: Orally administered dronabinol at a maximum dose of 10 mg daily or corresponding placebo for three weeks (15-21 days), separated by a three week washout period. MAIN OUTCOME MEASURE: Median spontaneous pain intensity (numerical rating scale) in the last week of treatment. RESULTS: Median spontaneous pain intensity was significantly lower during dronabinol treatment than during placebo treatment (4.0 (25th to 75th centiles 2.3 to 6.0) v 5.0 (4.0 to 6.4), P = 0.02), and median pain relief score (numerical rating scale) was higher (3.0 (0 to 6.7) v> 0 (0 to 2.3), P = 0.035). The number needed to treat for 50% pain relief was 3.5 (95% confidence interval 1.9 to 24.8). On the SF-36 quality of life scale, the two items bodily pain and mental health indicated benefits from active treatment compared with placebo. The number of patients with adverse events was higher during active treatment, especially in the first week of treatment. The functional ability of the multiple sclerosis patients did not change. CONCLUSIONS: Dronabinol has a modest but clinically relevant analgesic effect on central pain in patients with multiple sclerosis. Adverse events, including dizziness, were more frequent with dronabinol than with placebo during the first week of treatment.

Administration, Oral↗
PubMed2004

Valproic acid has no effect on pain in polyneuropathy: a randomized, controlled trial.

The aim of this randomized, double-blind, placebo-controlled cross-over study was to test whether valproic acid relieves painful polyneuropathy. Thirty-one patients completed two treatment phases of 4 weeks' duration with valproic acid (1,500 mg daily) and placebo. There was no significant difference between valproic acid and placebo in the rating of total pain (median, 5 in the valproic acid period vs 6 in the placebo period; p = 0.24) or in individual pain ratings.

Adult↗
PubMed2004

Evoked pain in the motor endplate region of the brachial biceps muscle: an experimental study.

Spontaneous electrical activity, interpreted as motor endplate activity, has been reported at muscle trigger points. This study examined whether the motor endplate region, identified by electromyography, is more sensitive to noxious stimuli than other muscle sites. We induced pain in the brachial biceps muscles of 21 healthy subjects by injecting capsaicin (30 microg/0.1 ml) and NaCl (5%/0.2 ml) in the motor endplate region and at electrically silent muscle sites. Needle and evoked pain were measured by a visual analogue scale (VAS) (0-10) and the short form of the McGill Pain Questionnaire. The needle pain in the motor endplate region differed both in intensity and quality from that at other sites. The maximal pain after NaCl 5% was higher, and the VAS area-under-the-curve for NaCl 5% and capsaicin were larger, in the motor endplate region than in other sites. A higher density of muscle nociceptors in the vicinity of the motor endplate region may account for the observed differences in pain. These findings may have clinical implications for the treatment of musculoskeletal pain conditions.

Adult↗
PubMed2004

Pain thresholds during and after treatment of severe depression with electroconvulsive therapy.

Pain and depression are often associated suggesting that both conditions share a common neurobiological mechanism, which modulate emotional function and processing of noxious information. Pain thresholds are hypothesized to be altered in depressed patients and normalized with the amelioration of depression. The purpose of this study was therefore to determine pain thresholds in patients during and after treatment with electroconvulsive therapy (ECT) of severe depression and in healthy controls. Seventeen depressed patients (Hamilton depression score > 18) and an age and gender matched control group of same size participated in the study. Pain detection and tolerance thresholds to pressure and pain tolerance thresholds to the Cold Pressor Test by exposure to ice-water was measured twice in depressed patients during and after ECT and twice in controls with a similar time interval. While ECT significantly improved Hamilton depression score (from mean 23.9 (SD:5) to mean 12.5 (SD:5.7)) there was no significant change in pain thresholds during and after ECT in the patient group. However, depressed patients had significantly lower pain tolerance in the Cold Pressor Test on both examinations and on pressure pain tolerance on the second examination day than their corresponding control subjects. The differential effect of ECT on depression score and pain processing indicate that mood and noxious processing are not medicated directly by the same systems but that a complex relationship between pain and depression exists.

Adolescent↗
PubMed2004

Chronic oral gabapentin reduces elements of central sensitization in human experimental hyperalgesia.

BACKGROUND: In chronic pain, increased activity from intact or damaged peripheral nerve endings results in an enhanced response in central pain transmission systems, a mechanism known as central sensitization. Central sensitization can also be invoked in human experimental models. Therefore, these models may be useful to characterize novel analgesics in humans. The anticonvulsant gabapentin has demonstrated efficacy in patients with neuropathic pain, but its mode of action remains unclear. This study examined the effects of gabapentin on signs of central sensitization (brush and pinprick hyperalgesia) in a human model of capsaicin-evoked pain, using a gabapentin dosing regimen similar to that used in the clinic. The aims were to determine whether gabapentin, dosed in a manner similar to that used in the clinic, affected the various components of central sensitization and to assess the utility of this model for characterizing novel analgesics. METHODS: Intradermal capsaicin (100 microg/20 microl) was administered in the volar forearm of 41 male human volunteers to induce pain and clinical signs of central sensitization. Gabapentin (titrated to 2,400 mg daily) or placebo was given orally for 15 days in a randomized, double-blind, parallel-group design. The capsaicin test was conducted at baseline and after gabapentin or placebo. Endpoints were the size of areas of brush-evoked allodynia (with cotton gauze) and pinprick hyperalgesia (with von Frey filament), and the intensity of ongoing brush- and pinprick-evoked pain. RESULTS: Gabapentin significantly reduced the area of brush allodynia compared with placebo (P </= 0.05) and insignificantly attenuated the area of pinprick hyperalgesia. Gabapentin had no significant effect on spontaneous and evoked pain intensity. CONCLUSION: Oral gabapentin, administered to healthy volunteers in a regimen similar to that used in treating chronic neuropathic pain, reduces measures of central sensitization evoked by intradermal capsaicin. This suggests that the pain-relieving effect in chronic neuropathic pain condition is linked to the effect of gabapentin on central sensitization. The ability of the capsaicin model to detect the efficacy of this standard treatment of neuropathic pain suggests that it may have a predictive value for detection of efficacy in human subjects.

Adult↗
PubMed2004

TDM-based imipramine treatment in neuropathic pain.

Tricyclic antidepressants (TCA) are the best-documented treatment of neuropathic pain. TCAs have a pronounced interindividual pharmacokinetic variability and a narrow therapeutic index. The aim of this study was to characterize the plasma concentration-effect relationship of imipramine in neuropathic pain and to determine the usefulness of therapeutic drug monitoring (TDM) of TCA treatment in a population with noncancer chronic pain. To do this, 83 patients with chronic noncancer neuropathic pain were included. Information on previous use of TCA was collected, and patients were tested for the presence of hyperalgesia. Pain intensity and pain relief were recorded, and the Short Form McGill Pain Questionnaire and Major Depression Inventory were completed before and during a TDM-based imipramine treatment. Imipramine dose was increased in steps of 25 mg/d every second week, and blood samples were taken at every dose. Endpoints were best possible pain relief, unacceptable side effects, or insufficient pain relief despite plasma drug level > 500 nmol/L. Dose range used was 10-300 mg/d. The study showed that imipramine 75 mg/d caused a 36-fold interindividual variation in steady-state plasma drug concentrations. In 46 responders (global pain relief > 25%) the plasma drug concentration at which an individual maximal analgesic effect was obtained ranged from 50 to 1400 nmol/L, but for the majority it was below 400 nmol/L. The concentration-effect relationship was similar for patients with central versus peripheral neuropathic pain and independent of the presence of hyperalgesia. Previous treatment failure with non-TDM TCA treatment was not a predictor of poor response to TDM-based treatment. In conclusion, there is a pronounced interindividual variability in concentration-effect relationship for imipramine treatment in neuropathic pain, but the majority of patients obtain a maximal analgesic effect at drug levels below 400 nmol/L. The concentration-effect relationship is similar for patients with central and peripheral neuropathic pain. Further studies are needed to document if TDM improves pain relief; however, TDM reduces the risk for toxicity.

Adult↗
PubMed2003

Development in pain and neurologic complaints after whiplash: a 1-year prospective study.

OBJECTIVE: To prospectively examine the course of pain and other neurologic complaints in patients with acute whiplash injury and in controls with acute ankle injury. METHODS: Patients with acute whiplash (n = 141) and ankle-injured controls (n = 40) were consecutively sampled, and underwent interview and examination after 1 week and 1, 3, 6, and 12 months. Outcome measures were pain intensity, pain frequency, and associated symptoms. RESULTS: Initial overall pain intensity above lower extremities (pain in neck, head, shoulder-arm, and low back) was similar in patients with whiplash (median Visual Analogue Scale [VAS](0-100) of 20 [25th and 75th percentile, 4, 39]) and ankle-injured controls (median VAS(0-100) of 15 [5, 34]). Whiplash-injured patients reported median overall VAS(0-100) pain intensity above lower extremities of 23 (12, 40) after 11 days and 14 (12, 40) after 1 year. Controls reported pain intensity of 0 (0, 4) after 12 days and 0 (0, 9) after 1 year. Reported overall pain frequency above lower extremities was 96% after 11 days and 74% after 1 year in whiplash-injured patients and 33% after 12 days and 47% after 1 year in controls. Associated neurologic symptoms were two to three times more common after whiplash injury. Correlation was found between pain intensity and associated symptoms in whiplash-injured patients but not controls. CONCLUSION: Pain occurs with high frequency but low intensity after whiplash and ankle injury. Associated neurologic symptoms were not correlated to pain in ankle-injured controls, but were correlated to pain in patients with whiplash injury. Persistent symptoms in whiplash-injured patients may be caused by both specific neck injury-related factors and nonspecific post-traumatic reactions. Disability was only encountered in the whiplash group.

Activities of Daily Living↗