Are sodium channel blockers useless in peripheral neuropathic pain?
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Clinical Trials as Topic↗
Biomedical subjects
Troels S Jensen
Publications and source records attributed to Troels S Jensen.
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↗
Pulsed radiofrequency: a novel treatment for chronic cervical radicular pain?
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Chronic Disease↗
[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↗
Persistent postsurgical pain: risk factors and prevention.
Acute postoperative pain is followed by persistent pain in 10-50% of individuals after common operations, such as groin hernia repair, breast and thoracic surgery, leg amputation, and coronary artery bypass surgery. Since chronic pain can be severe in about 2-10% of these patients, persistent postsurgical pain represents a major, largely unrecognised clinical problem. Iatrogenic neuropathic pain is probably the most important cause of long-term postsurgical pain. Consequently, surgical techniques that avoid nerve damage should be applied whenever possible. Also, the effect of aggressive, early therapy for postoperative pain should be investigated, since the intensity of acute postoperative pain correlates with the risk of developing a persistent pain state. Finally, the role of genetic factors should be studied, since only a proportion of patients with intraoperative nerve damage develop chronic pain. Based on information about the molecular mechanisms that affect changes to the peripheral and central nervous system in neuropathic pain, several opportunities exist for multimodal pharmacological intervention. Here, we outline strategies for identification of patients at risk and for prevention and possible treatment of this important entity of chronic pain.
Analgesics↗
Blink reflexes in patients with atypical odontalgia and matched healthy controls.
Atypical odontalgia (AO) is an orofacial pain condition which has been suggested to involve neuropathic pain mechanisms. The aim of this study was to use a brain stem reflex to investigate craniofacial nociceptive mechanisms in AO. In 38 AO patients and 27 matched healthy controls, the R2 component of the blink reflex (BR) was elicited using a "nociceptive-specific" electrode and recorded with surface electromyography electrodes on both orbicularis oculi muscles. The BR was tested by stimulation of both sides of the face of the participants before, during, and after an intraoral pain provocation test with capsaicin. The data were analyzed with three- and four-way mixed-model analyses of variance. The root mean square value of the ipsilateral R2 (R2i) was significantly reduced in patients compared with controls (P=0.046). No differences in R2 between stimulation sides were detected in either group (P>0.757). In all participants, R2 responses and the intensity of the pain evoked by the electrical stimulus were decreased during and after application of capsaicin compared with baseline (P<0.001). In patients, R2i onset latencies were significantly prolonged compared with controls (P=0.031). The present data show disturbances in the central processing of craniofacial information and that endogenous pain inhibitory systems in AO patients and healthy controls were activated to a similar degree by an acute intraoral nociceptive input. Additional clinical research with AO patients will be needed to determine to what extent neuropathic pain mechanisms are involved in this pain condition.
Adult↗
Mechanisms of disease: mechanism-based classification of neuropathic pain-a critical analysis.
Classification of neuropathic pain according to etiology or localization has clear limitations. The discovery of specific molecular and cellular events following experimental nerve injury has raised the possibility of classifying neuropathic pain on the basis of the underlying neurobiological mechanisms. Application of this approach in the clinic is problematic, however, owing to a lack of precise tools to assess symptoms and signs, and difficulties in correlating symptoms and signs with mechanisms. Development and validation of diagnostic methods to identify mechanisms, together with pharmacological agents that specifically target these mechanisms, seems to be the most logical and rational way of improving neuropathic pain treatment.
Analgesics↗
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↗
A randomized study of the effects of gabapentin on postamputation pain.
BACKGROUND: Pain after amputation is common but difficult to treat. Therefore, the authors examined whether postoperative treatment with gabapentin could reduce postamputation stump and phantom pain. METHODS: Forty-six patients scheduled to undergo lower limb amputation were randomly assigned to receive oral gabapentin or placebo. Treatment was started on the first postoperative day and continued for 30 days. The daily dose of gabapentin or placebo was gradually increased to 2,400 mg/day. The intensity of stump and phantom pain was recorded every day on a numeric rating scale (0-10) during the 30-day treatment period. Five interviews were performed after 7, 14, and 30 days and after 3 and 6 months. RESULTS: Results from 41 patients were included in the data analysis. The risk of phantom pain (gabapentin vs. placebo) was 55.0% versus 52.6% (risk difference, 2.4%; 95% confidence interval, -28.9 to 33.7%; P = 0.88; 30 days) and 58.8% versus 50.0% (risk difference, 8.8%; 95% confidence interval, -23.3 to 40.9%; P = 0.59; 6 months). The median intensity of phantom pain (gabapentin vs. placebo) was 1.5 (range, 0-9.0) versus 1.2 (range, 0-6.6) (P = 0.60; 30 days) and 1.0 (range, 0-6.0) versus 0.5 (range, 0-5.0) (P = 0.77; 6 months). The median intensity of stump pain was 0.85 (range, 0-8.2) versus 1.0 (range, 0-5.4) (P = 0.68; 30 days) and 0 (range, 0-8.0) versus 0 (range, 0-5.0) (P = 0.58; 6 months). CONCLUSION: Gabapentin administered in the first 30 postoperative days after amputation does not reduce the incidence or intensity of postamputation pain.
Aged↗
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↗
New perspectives on the management of diabetic peripheral neuropathic pain.
Peripheral neuropathy affects about 30% of people with diabetes mellitus. Between 16% and 26% of diabetes patients experience chronic pain. This may be referred to as diabetic neuropathic pain (DNP) or diabetic peripheral neuropathic pain (DPNP). Minimum requirements for diagnosis of DPNP should include assessment of pain and symptoms and neurological examination, with the accent on sensory examination. Given that depression and other co-morbidities are commonly associated with this condition, a broad approach to management is essential. Lifestyle intervention and optimisation of glycaemic control are recommended as initial steps in management. An evidence-based treatment algorithm for DPNP has been proposed, recommending initial use of either a tricyclic antidepressant, selective serotonin noradrenaline re-uptake inhibitor or alpha-2-delta agonist, depending on patient co-morbidities and contra-indications. Addition of an opioid agonist may be required in the event of inadequate pain control. Irrespective of which treatment is offered, only about one third of patients are likely to achieve more than 50% pain relief. Further research to improve the diagnosis and management of DPNP is needed.
Anticonvulsants↗
A PET activation study of brush-evoked allodynia in patients with nerve injury pain.
Acute experimental brush-evoked allodynia induces a cortical activation pattern that differs from that typically seen during experimental nociceptive pain. In this study, we used positron emission tomography to measure changes in regional cerebral blood flow (rCBF) in patients with clinical allodynia. Nine patients with peripheral nerve injury were scanned during rest, brush-evoked allodynia, and brushing of normal contralateral skin. PET data were analyzed for the whole group and for single subjects. Allodynic stimulation activated the contralateral orbitofrontal cortex (BA 11) in every patient. Whereas normal brushing activated most strongly the contralateral insular cortex, allodynic brushing produced an ipsilateral activation in this area. Another important difference between normal and allodynic brushing was the absence of a contralateral primary somatosensory cortex (SI) activation during allodynic brushing. No thalamic activation was observed during allodynic or control brushing. Although no anterior cingulate cortex (ACC) activation could be demonstrated in the group analysis, single subject analysis revealed that four patients activated this region during brush-evoked allodynia. A direct post hoc comparison of brush -and allodynia-induced rCBF changes showed that allodynia was associated with significantly stronger activations in orbitofrontal cortex and ipsilateral insula whereas non-painful brushing more strongly activated SI and BA 5/7. These findings indicate that activity in the cortical network involved in the sensory-discriminative processing of nociceptive pain is downregulated in neuropathic pain. Instead, there is an upregulation of activity in the orbitofrontal and insular cortices, which is probably due to the stronger emotional load of neuropathic pain and higher computational demands of processing a mixed sensation of brush and pain.
Adult↗
Analgesic efficacy and safety of intravenous paracetamol (acetaminophen) administered as a 2 g starting dose following third molar surgery.
BACKGROUND: The recommended dose for intravenous (IV) paracetamol injection in adults is 1g, however pharmacokinetic and pharmacodynamic findings suggest that a better analgesia could be obtained with a 2 g starting dose. METHODS: A single-centre, randomised, double-blind, placebo-controlled, 3-parallel group study was performed to demonstrate the analgesic efficacy and safety of IV paracetamol 2 g. Following third molar surgery, patients reporting moderate to severe pain received a single 15-min infusion of either IV paracetamol 2 g, IV paracetamol 1g or placebo. Efficacy and safety were evaluated over 8 h. Laboratory tests were performed before and 48 h after drug administration. RESULTS: Two hundred and ninety seven patients (132 = IV paracetamol 2g; 132 = IV paracetamol 1g; 33 = placebo) were randomised and completed the study. The summed pain relief over 6h (TOTPAR6) was significantly superior with IV paracetamol 2 g as compared to IV paracetamol 1g and placebo (p < 0.0001). Pain relief scores of IV paracetamol 2g were significantly superior to IV paracetamol 1g and to placebo from T30' to T8h (p < 0.0001). Median duration of analgesia was significantly longer following IV paracetamol 2 g compared to IV paracetamol 1g and placebo (p < 0.0001). Adverse events occurred with the same frequency in the 3 treatment groups. No clinically significant changes from baseline were observed for vital signs or laboratory tests. CONCLUSION: The analgesic efficacy of a 2 g starting dose of IV paracetamol was superior over the recommended dose of 1g in terms of magnitude and duration of analgesic effect for postoperative pain following third molar surgery, with no significant difference between groups regarding safety.
Acetaminophen↗
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↗
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↗
Antidepressants in the treatment of neuropathic pain.
Neuropathic pain is due to lesion or dysfunction of the peripheral or central nervous system. Tricyclic antidepressants and anticonvulsants have long been the mainstay of treatment of this type of pain. Tricyclic antidepressants may relieve neuropathic pain by their unique ability to inhibit presynaptic reuptake of the biogenic amines serotonin and noradrenaline, but other mechanisms such as N-methyl-D-aspartate receptor and ion channel blockade probably also play a role in their pain-relieving effect. The effect of tricyclic antidepressants in neuropathic pain in man has been demonstrated in numerous randomised, controlled trials, and a few trials have shown that serotonin noradrenaline and selective serotonin reuptake inhibitor antidepressants also relieve neuropathic pain although with lower efficacy. Tricyclic antidepressants will relieve one in every 2-3 patients with peripheral neuropathic pain, serotonin noradrenaline reuptake inhibitors one in every 4-5 and selective serotonin reuptake inhibitors one in every 7 patients. Thus, based on efficacy measures such as numbers needed to treat, tricyclic antidepressants tend to work better than the anticonvulsant gabapentin and treatment options such as tramadol and oxycodone, whereas the serotonin noradrenaline reuptake inhibitor venlafaxine appears to be equally effective with these drugs and selective serotonin reuptake inhibitors apparently have lower efficacy. Head-to-head comparisons between antidepressants and the other analgesics are lacking. Contraindications towards the use of tricyclic antidepressants and low tolerability in general of this drug class--may among the antidepressants--favour the use of the serotonin noradrenaline reuptake inhibitors. A recent study on bupropion, which is a noradrenaline and dopamine uptake inhibitor, indicated a surprisingly high efficacy of this drug in peripheral neuropathic pain. In conclusion, antidepressants represent useful tools in neuropathic pain treatment and must still be considered as first line treatments of neuropathic pain. However, without head-to-head comparisons between antidepressants and other analgesics, it is not possible to provide real evidence-based treatment algorithms for neuropathic pain.
Analgesics, Non-Narcotic↗
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↗
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↗