RESUMEN
We investigate the adhesion mechanism between an elastic strip of vinylpolysiloxane bent in a racquet-like shape, and a thick elastomeric substrate with the aim to understand how local swelling modifies adhesion. Using a modified loop-tack adhesion test, we place a droplet of silicone oil in between the two materials, vary the dwell time and measure the force required to separate the two interfaces. The experiments are then compared with an analytical model that describes how the critical peel force is modified as the interfacial surface energy changes over time. Our study reveals that in certain circumstances swelling can enhance adhesion. More specifically, strong adhesion is obtained when most of the droplet is absorbed by the solid. By contrast, when the droplet remains at the interface a small adhesive force is measured.
RESUMEN
BACKGROUND: Drugs are prescribed for chronic low back pain without knowing in advance whether a patient will respond to them or not. Quantitative sensory tests (QST) can discriminate patients according to sensory phenotype, possibly reflecting underlying mechanisms of pain processing. QST may therefore be a screening tool to identify potential responders to a certain drug. The aim of this study was to investigate whether QST can predict analgesic effects of oxycodone, imipramine and clobazam in chronic low back pain. METHODS: Oxycodone 15 mg (n = 50), imipramine 75 mg (n = 50) and clobazam 20 mg (n = 49) were compared to active placebo tolterodine 1 mg in a randomized, double-blinded, crossover fashion. Electrical, pressure and thermal QST were performed at baseline and after 1 and 2 h. Pain intensity was assessed on a 0-10 numeric rating scale every 30 min for up to 2 h. The ability of baseline QST to predict pain reduction after 2 h was analysed using linear mixed models. Genetic variants of drug-metabolizing enzymes and genes affecting pain sensitivity were examined as covariables. RESULTS: No predictor of analgesic effect was found for oxycodone and clobazam. Thermal QST was associated with analgesic effect of imipramine: patients more sensitive to heat or cold were more likely to experience an effect of imipramine. Pharmacogenetic variants and pain-related candidate genes were not associated with drug efficacy. CONCLUSIONS: Thermal QST have the potential to predict imipramine effect in chronic low back pain. Oxycodone and clobazam effects could not be predicted by any of the selected QST or genetic variants. SIGNIFICANCE: Predicting drug efficacy in chronic low back pain remains difficult. There is some evidence that patients more sensitive to heat and cold pain respond better to imipramine.
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Analgésicos/uso terapéutico , Clobazam/uso terapéutico , Imipramina/uso terapéutico , Dolor de la Región Lumbar/tratamiento farmacológico , Oxicodona/uso terapéutico , Umbral del Dolor/efectos de los fármacos , Adulto , Anciano , Analgésicos/administración & dosificación , Clobazam/administración & dosificación , Estudios Cruzados , Método Doble Ciego , Estimulación Eléctrica , Femenino , Humanos , Imipramina/administración & dosificación , Masculino , Persona de Mediana Edad , Oxicodona/administración & dosificación , Dimensión del Dolor , PresiónRESUMEN
BACKGROUND: Chronic pain is frequently associated with hypersensitivity of the nervous system, and drugs that increase central inhibition are therefore a potentially effective treatment. Benzodiazepines are potent modulators of GABAergic neurotransmission and are known to exert antihyperalgesic effects in rodents, but translation into patients are lacking. This study investigates the effect of the benzodiazepine clobazam in chronic low-back pain in humans. The aim of this study is to explore the effect of GABA modulation on chronic low-back pain and on quantitative sensory tests. METHODS: In this double-blind cross-over study, 49 patients with chronic low-back pain received a single oral dose of clobazam 20 mg or active placebo tolterodine 1 mg. Pain intensity on the 0-10 numeric rating scale and quantitative sensory tests were assessed during 2 h after drug intake. RESULTS: Pain intensity in the supine position was significantly reduced by clobazam compared to active placebo (60 min: 2.9 vs. 3.5, p = 0.008; 90 min: 2.7 vs. 3.3, p = 0.024; 120 min: 2.4 vs. 3.1, p = 0.005). Pain intensity in the sitting position was not significantly different between groups. No effects on quantitative sensory tests were observed. CONCLUSIONS: This study suggests that clobazam has an analgesic effect in patients with chronic low-back pain. Muscle relaxation or sedation may have contributed to the effect. Development of substances devoid of these side effects would offer the potential to further investigate the antihyperalgesic action of GABAergic compounds. SIGNIFICANCE: Modulation of GABAergic pain-inhibitory pathways may be a potential future therapeutic target.
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Anticonvulsivantes/uso terapéutico , Benzodiazepinas/uso terapéutico , Dolor Crónico/tratamiento farmacológico , Dolor de la Región Lumbar/tratamiento farmacológico , Umbral del Dolor/efectos de los fármacos , Adulto , Anciano , Clobazam , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Resultado del TratamientoRESUMEN
BACKGROUND: Chronic pain is associated with generalized hypersensitivity and impaired endogenous pain modulation (conditioned pain modulation; CPM). Despite extensive research, their prevalence in chronic pain patients is unknown. This study investigated the prevalence and potential determinants of widespread central hypersensitivity and described the distribution of CPM in chronic pain patients. METHODS: We examined 464 consecutive chronic pain patients for generalized hypersensitivity and CPM using pressure algometry at the second toe and cold pressor test. Potential determinants of generalized central hypersensitivity were studied using uni- and multivariate regression analyses. Prevalence of generalized central hypersensitivity was calculated for the 5th, 10th and 25th percentile of normative values for pressure algometry obtained by a previous large study on healthy volunteers. CPM was addressed on a descriptive basis, since normative values are not available. RESULTS: Depending on the percentile of normative values considered, generalized central hypersensitivity affected 17.5-35.3% of patients. 23.7% of patients showed no increase in pressure pain threshold after cold pressor test. Generalized central hypersensitivity was more frequent and CPM less effective in women than in men. Unclearly classifiable pain syndromes showed higher frequencies of generalized central hypersensitivity than other pain syndromes. CONCLUSIONS: Although prevalent in chronic pain, generalized central hypersensitivity is not present in every patient. An individual assessment is therefore required in order to detect altered pain processing. The broad basic knowledge about central hypersensitivity now needs to be translated into concrete clinical consequences, so that patients can be offered an individually tailored mechanism-based treatment.
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Dolor Crónico/fisiopatología , Hiperalgesia/epidemiología , Adulto , Anciano , Dolor Crónico/complicaciones , Femenino , Humanos , Hiperalgesia/complicaciones , Masculino , Persona de Mediana Edad , Dimensión del Dolor/métodos , Umbral del Dolor/fisiología , Presión , PrevalenciaRESUMEN
BACKGROUND: Ilioinguinal (IL) and iliohypogastric (IH) nerve blocks are used in patients with chronic postherniorrhaphy pain. The present study tested the hypothesis that our method, previously developed in cadavers, blocks the nerves separately and selectively in human volunteers. METHODS: We blocked the IL and the IH nerves in 16 volunteers in a single-blinded randomized cross-over setting under direct ultrasound visualization, by injecting two times the ED95 volume of 1% mepivacaine needed to block a peripheral nerve. The anaesthetized skin areas were tested by pinprick and marked on the skin. A digital photo was taken. For further analysis, the parameterized picture data were transformed into a standardized and unified coordinate system to compare and calculate the overlap of the anaesthetized skin areas of the two nerves on each side. An overlap <25% was defined as selective block. RESULTS: Fifty nerve blocks could be analysed. The mean volume injected to block a single nerve was 0.9 ml. Using ultrasound, we observed spread from one nerve to the other in 12% of cases. The overlap of the anaesthetized skin areas of the nerves was 60.3% and did not differ after exclusion of the cases with visible spread of local anaesthetic from one nerve to the other. CONCLUSIONS: The IL and IH nerves cannot be selectively blocked even if volumes below 1 ml are used. The most likely explanation is the spread of local anaesthetic from one nerve to the other, although this could not be directly observed in most cases.
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Plexo Hipogástrico/diagnóstico por imagen , Bloqueo Nervioso/métodos , Nervios Periféricos/efectos de los fármacos , Nervios Periféricos/diagnóstico por imagen , Adolescente , Adulto , Anestésicos Locales/administración & dosificación , Estudios Cruzados , Femenino , Humanos , Conducto Inguinal/diagnóstico por imagen , Conducto Inguinal/inervación , Plexo Lumbosacro/diagnóstico por imagen , Masculino , Mepivacaína/administración & dosificación , Persona de Mediana Edad , Método Simple Ciego , Ultrasonografía , Adulto JovenRESUMEN
BACKGROUND: To compare 4 different treatment strategies in patients with late whiplash syndrome. METHODS: Patients were randomly assigned to one of the following treatment groups: infiltration, physiotherapy, or medication. Group allocation was stratified according to gender, age, and education. Additionally, patients of each group were randomized 1:1 to cognitive-behavioral therapy (CBT) or no CBT. Patients were assessed at baseline, after an 8-week treatment period, and 3 and 6 months later. Main outcome measures were subjective outcome rating, pain intensity, and working ability. RESULTS: Of 91 enrolled patients, 73 completed the study; 62% were women. After treatment, 47 patients (64%) were subjectively improved (48%), or free of symptoms (16%), with a preponderance of women (73% vs 50%, p = 0.047). There was no difference regarding outcomes among the 3 treatment groups in men and women. The most robust difference was achieved with CBT, associated with a higher rate of recovery (23% vs 9%), and improvement (53% vs 42%) (p = 0.024), and with a gender difference (p = 0.01). All treatments significantly improved pain intensity and working ability. CONCLUSION: Intensive therapy in late whiplash syndrome can achieve improvement of different outcome measures including working ability in two-thirds of patients, more effective in women, persisting beyond 6 months in half. Additional cognitive-behavioral therapy was the most effective treatment modality. CLASSIFICATION OF EVIDENCE: This interventional study provides Class III evidence that CBT used as an adjunct to infiltration, medication, or physiotherapy increases improvement rates in persons with late whiplash syndrome.
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Bupivacaína/uso terapéutico , Terapia Cognitivo-Conductual/métodos , Flurbiprofeno/uso terapéutico , Modalidades de Fisioterapia , Lesiones por Latigazo Cervical/terapia , Adolescente , Adulto , Anestésicos Locales/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Terapia Combinada , Femenino , Humanos , Seguro por Discapacidad , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Selección de Paciente , Estudios Prospectivos , Factores Sexuales , Estadísticas no Paramétricas , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
BACKGROUND: Local anaesthetic blocks of the greater occipital nerve (GON) are frequently performed in different types of headache, but no selective approaches exist. Our cadaver study compares the sonographic visibility of the nerve and the accuracy and specificity of ultrasound-guided injections at two different sites. METHODS: After sonographic measurements in 10 embalmed cadavers, 20 ultrasound-guided injections of the GON were performed with 0.1 ml of dye at the classical site (superior nuchal line) followed by 20 at a newly described site more proximal (C2, superficial to the obliquus capitis inferior muscle). The spread of dye and coloration of nerve were evaluated by dissection. RESULTS: The median sonographic diameter of the GON was 4.2 x 1.4 mm at the classical and 4.0 x 1.8 mm at the new site. The nerves were found at a median depth of 8 and 17.5 mm, respectively. In 16 of 20 in the classical approach and 20 of 20 in the new approach, the nerve was successfully coloured with the dye. This corresponds to a block success rate of 80% (95% confidence interval: 58-93%) vs 100% (95% confidence interval: 86-100%), which is statistically significant (McNemar's test, P=0.002). CONCLUSIONS: Our findings confirm that the GON can be visualized using ultrasound both at the level of the superior nuchal line and C2. This newly described approach superficial to the obliquus capitis inferior muscle has a higher success rate and should allow a more precise blockade of the nerve.
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Bloqueo Nervioso/métodos , Nervios Espinales/diagnóstico por imagen , Ultrasonografía Intervencional/métodos , Anciano , Anciano de 80 o más Años , Disección/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cuello/anatomía & histología , Cuello/diagnóstico por imagen , Músculos del Cuello/diagnóstico por imagen , Nervios Espinales/anatomía & histologíaRESUMEN
Our study group recently evaluated an ED(95) local anaesthetic volume of 0.11 ml.mm(-2) cross-sectional nerve area for the ulnar nerve. This prospective, randomised, double-blind crossover study investigated whether this volume is sufficient for brachial plexus blocks at the axillary level. Ten volunteers received an ultrasonographic guided axillary brachial plexus block either with 0.11 ('low' volume) or 0.4 ('high' volume) ml.mm(-2) cross-sectional nerve area with mepivacaine 1%. The mean (SD) volume was in the low volume group 4.0 (1.0) and 14.8 (3.8) ml in the high volume group. The success rate for the individual nerve blocks was 27 out of 30 in the low volume group (90%) and 30 out of 30 in the high volume group (100%), resulting in 8 out of 10 (80%) vs 10 out of 10 (100%) complete blocks in the low vs the high volume groups, respectively (NS). The mean (SD) sensory onset time was 25.0 (14.8) min in the low volume group and 15.8 (6.8) min in the high volume group (p < 0.01). The mean (SD) duration of sensory block was 125 (38) min in the low volume group and 152 (70) min in the high volume group (NS). This study confirms our previous published ED(95) volume for mepivacaine 1% to block peripheral nerves. The volume of local anaesthetic has some influence on the sensory onset time.
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Anestésicos Locales/administración & dosificación , Plexo Braquial , Bloqueo Nervioso/métodos , Adulto , Axila , Índice de Masa Corporal , Estudios Cruzados , Método Doble Ciego , Esquema de Medicación , Humanos , Nervio Mediano/diagnóstico por imagen , Estudios Prospectivos , Nervio Radial/diagnóstico por imagen , Sensación/efectos de los fármacos , Nervio Cubital/diagnóstico por imagen , Ultrasonografía Intervencional/métodos , Adulto JovenRESUMEN
Perceptual-cognitive impairment after general anaesthesia may affect the ability to reliably report pain severity with the standard visual analog scale (VAS). To minimise these limitations, we developed 'PAULA the PAIN-METER' (PAULA): it has five coloured emoticon faces on the forefront, it is twice as long as a standard VAS scale, and patients use a slider to mark their pain experience. Forty-eight postoperative patients rated descriptive pain terms on PAULA and on a standard VAS immediately after admission and before discharge from the postanaesthesia care unit. Visual acuity was determined before both assessments. The values obtained with PAULA showed less variance than those obtained with the standard VAS, even at the first assessment, where only 23% of the patients had regained their visual acuity. Furthermore, the deviations of the absolute VAS values in individual patients for each descriptive pain term were significantly smaller with PAULA than with the standard VAS.
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Dimensión del Dolor/métodos , Dolor Postoperatorio/diagnóstico , Adulto , Anciano , Anestesia General , Expresión Facial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor/instrumentación , Psicometría , Reproducibilidad de los Resultados , Agudeza Visual , Adulto JovenRESUMEN
BACKGROUND: Ilioinguinal and iliohypogastric nerve blocks may be used in the diagnosis of chronic groin pain or for analgesia for hernia repair. This study describes a new ultrasound-guided approach to these nerves and determines its accuracy using anatomical dissection control. METHODS: After having tested the new method in a pilot cadaver, 10 additional embalmed cadavers were used to perform 37 ultrasound-guided blocks of the ilioinguinal and iliohypogastric nerve. After injection of 0.1 ml of dye the cadavers were dissected to evaluate needle position and colouring of the nerves. RESULTS: Thirty-three of the thirty-seven needle tips were located at the exact target point, in or directly at the ilioinguinal or iliohypogastric nerve. In all these cases the targeted nerve was coloured entirely. In two of the remaining four cases parts of the nerves were coloured. This corresponds to a simulated block success rate of 95%. In contrast to the standard 'blind' techniques of inguinal nerve blocks we visualized and targeted the nerves 5 cm cranial and posterior to the anterior superior iliac spine. The median diameters of the nerves measured by ultrasound were: ilioinguinal 3.0x1.6 mm, and iliohypogastric 2.9x1.6 mm. The median distance of the ilioinguinal nerve to the iliac bone was 6.0 mm and the distance between the two nerves was 10.4 mm. CONCLUSIONS: The anatomical dissections confirmed that our new ultrasound-guided approach to the ilioinguinal and iliohypogastric nerve is accurate. Ultrasound could become an attractive alternative to the 'blind' standard techniques of ilioinguinal and iliohypogastric nerve block in pain medicine and anaesthetic practice.
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Bloqueo Nervioso/métodos , Nervios Periféricos/diagnóstico por imagen , Abdomen/inervación , Músculos Abdominales , Pared Abdominal , Anciano , Anciano de 80 o más Años , Cadáver , Colorantes , Disección/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nervios Periféricos/anatomía & histología , Transductores , UltrasonografíaRESUMEN
BACKGROUND: Thoracoscopic surgery can be associated with considerable postoperative pain. While the benefits of paravertebral block on pain after thoracotomy have been demonstrated, no investigations on the effects of paravertebral block on pain after thoracoscopy have been conducted. We tested the hypothesis that a single-injection thoracic paravertebral block, performed preoperatively, reduces pain scores after thoracoscopic surgery. METHODS: Of 45 patients recruited, 40 completed the study. They were randomly allocated to two groups: the paravertebral group received i.v. patient-controlled analgesia (PCA) with morphine plus single-injection thoracic paravertebral block with bupivacaine 0.375% and adrenaline 1:200 000 0.4 ml kg(-1) (n=20). The control group was treated with a back puncture without injection and morphine PCA (n=20). RESULTS: The main outcomes recorded during 48 h after surgery were pain scores using the visual analogue scale (VAS, 0-100). Secondary outcomes were cumulative morphine consumption and peak expiratory flow rate (PEFR). Half an hour and 24 h after surgery, median (25th-75th percentiles) VAS on coughing in the paravertebral group was 31.0 (20.0-55.0) and 30.5 (17.5-40.0) respectively and in the control group it was 70.0 (30.0-100.0) and 50.0 (25.0-75.0) respectively. The difference between the groups over the whole observation period was statistically significant (P<0.05). Twenty-four and 48 h after surgery, median (25th-75th percentiles) cumulative morphine consumption (mg) was 49.0 (38.3-87.0) and 69.3 (38.8-118.5) respectively in the paravertebral group and 51.2 (36.0-84.1) and 78.1 (38.4-93.1) in the control group (statistically not significant). No differences were found in PEFR or the incidence of any side-effects between groups. CONCLUSION: We conclude that single-shot preoperative paravertebral block improves post-operative pain treatment after thoracoscopic surgery in a clinically significant fashion.
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Bloqueo Nervioso/métodos , Dolor Postoperatorio/prevención & control , Cirugía Torácica Asistida por Video , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Analgesia Controlada por el Paciente , Analgésicos Opioides/administración & dosificación , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Cuidados Intraoperatorios/métodos , Masculino , Persona de Mediana Edad , Morfina/administración & dosificación , Dimensión del Dolor/métodos , Ápice del Flujo Espiratorio/efectos de los fármacos , Estudios ProspectivosRESUMEN
BACKGROUND: Adding ketamine to morphine for patient-controlled analgesia (PCA) may be useful. However, data on this drug combination have been collected on small sample sizes. In order to evaluate the safety of the combination morphine- ketamine, we conducted a prospective study on a large patient population. METHODS: Patient-controlled analgesia was performed with 1026 patients using morphine and ketamine in a dose ratio of 1:1. All patients were treated in the ward. Prospectively collected data included incidence of complications and side-effects, verbal pain scores at rest and during mobilization (0 = no pain to 4 = very strong pain), consumption of morphine and ketamine and patient satisfaction (0 = very un-satisfied to 3 = very satisfied). RESULTS: The study included 462 women and 564 men who underwent, on average, 71.8 h (+/-56.1) of PCA. There were 698 orthopaedic, 160 abdominal, 96 thoracic, 20 vascular, 16 plastic, 15 neurosurgical, 11 urologic and 10 other surgical procedures. No complication was observed. Incidence of side-effects was: 1.2% respiratory depression, 23.5% nausea, 6.2% vivid dreams and/or hallucinations, 21.4% sedation and 10.3% pruritus. Reasons for discontinuing the PCA were side-effects (7.0%) and other (0.5%). Mean pain scores over the whole period were 0.44 (+/-0.54) at rest and 1.36 (+/-0.62) during mobilization. Mean satisfaction score was 2.52 (+/-0.69). CONCLUSION: Patient-controlled analgesia with morphine and ketamine is safe. It produces side-effects which, however, are infrequently a reason for discontinuing the regimen. It is also associated with low pain scores and high patient satisfaction.
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Analgésicos Opioides/efectos adversos , Anestésicos Disociativos/efectos adversos , Ketamina/efectos adversos , Morfina/efectos adversos , Dolor Postoperatorio/complicaciones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Analgesia Controlada por el Paciente , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/uso terapéutico , Anestésicos Disociativos/administración & dosificación , Anestésicos Disociativos/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Dipirona/uso terapéutico , Combinación de Medicamentos , Femenino , Humanos , Ketamina/administración & dosificación , Ketamina/uso terapéutico , Ketorolaco/uso terapéutico , Masculino , Persona de Mediana Edad , Morfina/administración & dosificación , Morfina/uso terapéutico , Dimensión del Dolor/efectos de los fármacos , Dolor Postoperatorio/tratamiento farmacológico , Satisfacción del Paciente , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Despite extensive use, different aspects of the pharmacological action of epidural fentanyl have not been clarified. We applied a multi-modal sensory test procedure to investigate the effect of epidural fentanyl on segmental spread, temporal summation (as a measure for short-lasting central hyperexcitability) and muscle pain. METHODS: Thirty patients received either placebo, 50 or 100 micro g single dose of fentanyl epidurally (L2-3), in a randomized, double-blind fashion. Heat pain tolerance thresholds at eight dermatomes from S1 to fifth cranial nerve (assessment of segmental spread), pain threshold to transcutaneous repeated electrical stimulation of the sural nerve (assessment of temporal summation) and pain intensity after injection of hypertonic saline into the tibialis anterior muscle (assessment of muscle pain) were recorded. RESULTS: Fentanyl 100 micro g, but not 50 micro g, produced analgesia to heat stimulation only at L2. Surprisingly, no effect at S1 was detected. Both fentanyl doses significantly increased temporal summation threshold and decreased muscle pain intensity. CONCLUSIONS: The findings suggest that a single lumbar epidural dose of fentanyl should be injected at the spinal interspace corresponding to the dermatomal site of pain. Increased effect on L2 compared with S1 suggests that drug effect on spinal nerve roots and binding to opioid receptors on the dorsal root ganglia may be more important than traditionally believed for the segmental effect of epidurally injected fentanyl. Epidural fentanyl increases temporal summation threshold and could therefore contribute to prevention and treatment of central hypersensitivity states. I.M. injection of hypertonic saline is a sensitive technique for detecting the analgesic action of epidural opioids.
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Analgesia Epidural , Analgésicos Opioides/farmacología , Fentanilo/farmacología , Umbral del Dolor/efectos de los fármacos , Adulto , Anciano , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Estimulación Eléctrica , Femenino , Calor , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Musculares/prevención & control , Dolor/prevención & control , Dimensión del Dolor/métodos , Nervio Sural/fisiologíaRESUMEN
OBJECTIVE: The authors aimed to provide an educational update on the current evidence of the effectiveness of drug therapy in the treatment of musculoskeletal pain and to offer a perspective of possible future developments. DESIGN: The authors used a pragmatic review of data provided by available systematic reviews and seminal controlled studies pertaining to the treatment of regional musculoskeletal pain problems. RESULTS: Epidural steroids may offer limited, short-term benefit for sciatica. Local injections of steroids are either ineffective or provide short-lasting benefits. Nonsteroidal anti-inflammatory drugs and opioids reduce pain, but the effect size is modest. The literature does not support convincingly the use of antidepressants. Certain muscle relaxants may be useful in the treatment of back pain. Hyaluronic acid, neutraceutical agents, avocado-soybean unsaponifiable agents, oxaceprol and diacerein may be effective in the treatment of osteoarthritis, but the information regarding these new agents does not allow wholesale endorsement of these substances. Selective epidural injection of steroids at a target nerve root approached through the intervertebral foramin has the potential to replace the traditional epidural approach. Long-acting, C--fiber-specific local anesthetics are under investigation and could provide long-lasting pain relief without motor or sensory impairment. In the future, central hypersensitivity in chronic musculoskeletal pain might be treated using antagonists of the N-methyl-D-aspartate receptor. Cannabinoid agents produce antinociception and prevent experimentally induced hyperalgesia in animals, and they may find a role in pain management. Methods to optimize drug combinations are available. CONCLUSIONS: The effectiveness of the currently available drugs in the treatment of musculoskeletal pain conditions is disappointing. Recent developments may open new perspectives in this area of pain medicine.
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Enfermedades Musculoesqueléticas/tratamiento farmacológico , Dolor/tratamiento farmacológico , Cuidados Paliativos/métodos , Cuidados Paliativos/tendencias , Animales , HumanosRESUMEN
OBJECTIVE: The mechanisms underlying chronic pain after whiplash injury are usually unclear. Injuries may cause sensitization of spinal cord neurons in animals (central hypersensitivity), which results in increased responsiveness to peripheral stimuli. In humans, the responsiveness of the central nervous system to peripheral stimulation may be explored by applying sensory tests to healthy tissues. The hypotheses of this study were: (1) chronic whiplash pain is associated with central hypersensitivity; (2) central hypersensitivity is maintained by nociception arising from the painful or tender muscles in the neck. DESIGN: Comparison of patients with healthy controls. SETTING: Pain clinic and laboratory for pain research, university hospital. PATIENTS: Fourteen patients with chronic neck pain after whiplash injury (car accident) and 14 healthy volunteers. OUTCOME MEASURES: Pain thresholds to: single electrical stimulus (intramuscular), repeated electrical stimulation (intramuscular and transcutaneous), and heat (transcutaneous). Each threshold was measured at neck and lower limb, before and after local anesthesia of the painful and tender muscles of the neck. RESULTS: The whiplash group had significantly lower pain thresholds for all tests. except heat, at both neck and lower limb. Local anesthesia of the painful and tender points affected neither intensity of neck pain nor pain thresholds. CONCLUSIONS: The authors found a hypersensitivity to peripheral stimulation in whiplash patients. Hypersensitivity was observed after cutaneous and muscular stimulation, at both neck and lower limb. Because hypersensitivity was observed in healthy tissues, it resulted from alterations in the central processing of sensory stimuli (central hypersensitivity). Central hypersensitivity was not dependent on a nociceptive input arising from the painful and tender muscles.
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Sistema Nervioso Central/fisiopatología , Hiperalgesia/etiología , Hiperalgesia/fisiopatología , Dolor de Cuello/etiología , Dolor de Cuello/fisiopatología , Lesiones por Latigazo Cervical/complicaciones , Adulto , Enfermedad Crónica , Estimulación Eléctrica , Femenino , Calor , Humanos , Pierna/fisiopatología , Masculino , Persona de Mediana Edad , Umbral del Dolor , Valores de Referencia , Lesiones por Latigazo Cervical/fisiopatologíaRESUMEN
In experimental studies, drug-induced analgesia is usually assessed by cutaneous stimulation. If analgesics act differently on cutaneous and deep nociception, the results of these studies may not be entirely applicable to clinical pain involving deep structures. We tested the hypothesis that opioids have different abilities to inhibit cutaneous and muscular pain. Either the opioid remifentanil or placebo was infused in 12 healthy volunteers in a cross-over fashion. Repeated electrical stimulation (five impulses at 2 Hz) was applied to both skin and muscle. Pain thresholds were recorded. Remifentanil caused a higher increase in the muscular pain thresholds than in the cutaneous pain thresholds (P = 0.035). We conclude that opioids inhibit muscular pain more strongly than cutaneous pain in humans.
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Analgésicos Opioides/uso terapéutico , Músculo Esquelético/inervación , Umbral del Dolor/efectos de los fármacos , Dolor/prevención & control , Piperidinas/uso terapéutico , Piel/inervación , Adulto , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Estimulación Eléctrica , Femenino , Humanos , Masculino , Especificidad de Órganos , RemifentaniloRESUMEN
BACKGROUND: The authors applied an optimization model (direct search) to find the optimal combination of bupivacaine dose, fentanyl dose, clonidine dose, and infusion rate for continuous postoperative epidural analgesia. METHODS: One hundred ninety patients undergoing 48-h thoracic epidural analgesia after major abdominal surgery were studied. Combinations of the variables of bupivacaine dose, fentanyl dose, clonidine dose, and infusion rate were investigated to optimize the analgesic effect (monitored by verbal descriptor pain score) under restrictions dictated by the incidence and severity of side effects. Six combinations were empirically chosen and investigated. Then a stepwise optimization model was applied to determine subsequent combinations until no decrease in the pain score after three consecutive steps was obtained. RESULTS: Twenty combinations were analyzed. The optimization procedure led to a reduction in the incidence of side effects and in the mean pain scores. The three best combinations of bupivacaine dose (mg/h), fentanyl dose (microg/h), clonidine dose (microg/h), and infusion rate (ml/h) were: 9-21-5-7, 8-30-0-9, and 13-25-0-9, respectively. CONCLUSIONS: Given the variables investigated, the aforementioned combinations may be the optimal ones to provide postoperative analgesia after major abdominal surgery. Using the direct search method, the enormous number of possible combinations of a therapeutic strategy can be reduced to a small number of potentially useful ones. This is accomplished using a scientific rather than an arbitrary procedure.
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Agonistas alfa-Adrenérgicos/uso terapéutico , Analgesia Epidural , Analgésicos Opioides/uso terapéutico , Anestésicos Locales/uso terapéutico , Bupivacaína/uso terapéutico , Clonidina/uso terapéutico , Fentanilo/uso terapéutico , Dolor Postoperatorio/tratamiento farmacológico , Agonistas alfa-Adrenérgicos/administración & dosificación , Agonistas alfa-Adrenérgicos/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Analgesia Epidural/efectos adversos , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/efectos adversos , Anestesia General , Anestésicos Locales/administración & dosificación , Anestésicos Locales/efectos adversos , Bupivacaína/administración & dosificación , Bupivacaína/efectos adversos , Clonidina/administración & dosificación , Clonidina/efectos adversos , Combinación de Medicamentos , Femenino , Fentanilo/administración & dosificación , Fentanilo/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Modelos Biológicos , Dimensión del Dolor/efectos de los fármacosAsunto(s)
Anestesia de Conducción , Dimensión del Dolor/métodos , Estimulación Física/métodos , Capsaicina/administración & dosificación , Estimulación Eléctrica , Potenciales Evocados Somatosensoriales , Humanos , Dolor/tratamiento farmacológico , Dolor/fisiopatología , Umbral del Dolor , Estimulación Física/instrumentación , Torniquetes , Estimulación Eléctrica Transcutánea del NervioRESUMEN
OBJECTIVE: To test the following hypotheses: there is a correlation between spread of epidural analgesia as assessed postoperatively by pinprick/cold test and postoperative pain intensity; block of pinprick/cold sensation is associated with absence of postoperative pain. DESIGN: Correlation analysis on prospectively collected data. SETTING: University hospital. PATIENTS: One hundred patients undergoing major surgery. Consecutive sample. INTERVENTIONS: Patients received an epidural infusion of bupivacaine 1 mg/ml, fentanyl 2 microg/ml, and epinephrine 2 microg/ml for at least 48 hours postoperatively. The infusion rate was adjusted according to pain intensity, occurrence of hypotension, or motor block. OUTCOME MEASURES: Assessments were made on three time points: 20-24 hours, 32-36 hours, and 4248 hours after extubation. Assessments included pinprick and cold sensitivity from C2 to S5, pain intensity (visual analogue scale, VAS) at rest, after cough, and after mobilization. Data were analyzed by multiple regression. RESULTS: VAS significantly decreased with increasing spread (number of dermatomes for which hyposensitivity to pinprick or cold was observed). Spread could explain only 2-5% of the variability of VAS. Absence of both pinprick and cold sensation at all dermatomes corresponding to the surgical wound was frequently associated with pain. A high proportion of patients manifesting an upper level of block above T5 had pain after abdominal surgery. CONCLUSIONS: Spread and efficacy of epidural analgesia as assessed by pinprick and cold stimulation correlate poorly with postoperative pain. These methods are of limited value both as clinical indicators of the efficacy of postoperative pain control and for investigating the effect of epidural drugs and techniques.
Asunto(s)
Analgesia Epidural , Dimensión del Dolor/efectos de los fármacos , Dolor Postoperatorio/tratamiento farmacológico , Adulto , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/uso terapéutico , Anestésicos Locales/administración & dosificación , Anestésicos Locales/uso terapéutico , Bupivacaína/administración & dosificación , Bupivacaína/uso terapéutico , Frío , Epinefrina/administración & dosificación , Epinefrina/uso terapéutico , Femenino , Fentanilo/administración & dosificación , Fentanilo/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Estimulación Física , Valor Predictivo de las Pruebas , Estudios Prospectivos , Análisis de Regresión , Vasoconstrictores/administración & dosificación , Vasoconstrictores/uso terapéuticoRESUMEN
BACKGROUND: The risk/benefit ratio of adding fentanyl, adrenaline and clonidine to epidural local anaesthetics for improving intraoperative analgesia is unclear. This meta-analysis was performed to clarify this issue. METHODS: Trials retrieved by search were considered if they were prospective, controlled, epidural analgesia (without combining general anaesthesia) was planned and occurrence of pain during surgery or side-effects were reported. Papers entered meta-analysis if they reached a predefined minimum quality score. Pooled odds ratios (OR) and confidence intervals (CI) were computed. P < 0.05 was considered as significant. RESULTS: Eighteen trials were included in the analysis for fentanyl. Fentanyl decreased the likelihood of pain (OR = 0.21, 95% CI = 0.15-0.30, P < 0.001) and increased the incidence of pruritus (OR = 5.59, 95% CI = 3.12-10.05, P < 0.001) and sedation (OR = 1.88, 95% CI = 1.19-2.98, P = 0.003), compared to control (local anaesthetic without fentanyl). Fentanyl had no effect on respiratory depression, nausea, vomiting and Apgar score. One case of respiratory depression of a newborn was observed. Because of the very low number of trials selected, evaluation of adrenaline and clonidine was not feasible. CONCLUSION: The analysis of current literature shows that the addition of fentanyl to local anaesthetics for intraoperative epidural analgesia is safe and advantageous. The reduction in the incidence of pain during surgery is quantitatively high and therefore clinically significant. Side-effects are mild. Randomized, controlled trials have to be performed in order to clarify the role of adrenaline and clonidine as epidural adjuvants for surgical analgesia.