The effect of surface wave propagation on neural responses to vibration in primate glabrous skin

Because tactile perception relies on the response of large populations of receptors distributed across the skin, we seek to characterize how a mechanical deformation of the skin at one location affects the skin at another. To this end, we introduce a novel non-contact method to characterize the surface waves produced in the skin under a variety of stimulation conditions. Specifically, we deliver vibrations to the fingertip using a vibratory actuator and measure, using a laser Doppler vibrometer, the surface waves at different distances from the locus of stimulation. First, we show that a vibration applied to the fingertip travels at least the length of the finger and that the rate at which it decays is dependent on stimulus frequency. Furthermore, the resonant frequency of the skin matches the frequency at which a subpopulation of afferents, namely Pacinian afferents, is most sensitive. We show that this skin resonance can lead to a two-fold increase in the strength of the response of a simulated afferent population. Second, the rate at which vibrations propagate across the skin is dependent on the stimulus frequency and plateaus at 7 m/s. The resulting delay in neural activation across locations does not substantially blur the temporal patterning in simulated populations of afferents for frequencies less than 200 Hz, which has important implications about how vibratory frequency is encoded in the responses of somatosensory neurons. Third, we show that, despite the dependence of decay rate and propagation speed on frequency, the waveform of a complex vibration is well preserved as it travels across the skin. Our results suggest, then, that the propagation of surface waves promotes the encoding of spectrally complex vibrations as the entire neural population is exposed to essentially the same stimulus. We also discuss the implications of our results for biomechanical models of the skin.     

Predatory bug <Emphasis Type="Italic">Picromerus bidens</Emphasis> communicates at different frequency levels

The Asopinae (Heteroptera: Pentatomidae) are a subfamily of stinkbugs with predaceous feeding habits and poorly understood communication systems. In this study we recorded vibratory signals emitted by Picromerus bidens L. on a non-resonant substrate and investigated their frequency characteristics. Males and females produced signals by vibration of the abdomen and tremulation. The female and male songs produced by abdominal vibrations showed gender-specific time structure. There were no differences in the temporal patterns of male or female tremulatory signals. The signals produced by abdominal vibrations were emitted below 600 Hz whereas tremulatory signals had frequency ranges extending up to 4 kHz. Spectra of male vibratory signals produced by abdominal vibrations contained different peaks, each of which may be dominant within the same song sequence. Males alternated with each other during production of rivalry signals, using different dominant frequency levels. We show that the vibratory song repertoire of P. bidens is broader than those of other predatory stinkbugs that have been investigated. The emission of vibrational signals with different dominant frequencies but the same production mechanism has not yet been described in heteropteran insects, and may facilitate location of individual sources of vibration within a group.     

Single-dose oral naproxen for acute postoperative pain: a quantitative systematic review

BACKGROUND: Naproxen and naproxen sodium are non-steroidal anti-inflammatory drugs used in a variety of painful conditions, including the treatment of postoperative pain. This review aims to assess the efficacy, safety and duration of action of a single oral dose of naproxen/naproxen sodium for moderate to severe acute postoperative pain in adults, compared with placebo. METHODS: The Cochrane Library (issue 4 2002), EMBASE, PubMed, MEDLINE and an in-house database were searched for randomised, double blind, placebo controlled trials of a single dose of orally administered naproxen or naproxen sodium in adults with acute postoperative pain. Pain relief or pain intensity data were extracted and converted into dichotomous information to give the number of patients with at least 50% pain relief over 4 to 6 hours. Relative benefit and number-needed-to-treat were then calculated. The percentage of patients with any adverse event, number-needed-to-harm, and time to remedication were also calculated. RESULTS: Ten trials with 996 patients in met the inclusion criteria. Six trials compared naproxen sodium 550 mg (252 patients) with placebo (248 patients); the NNT for at least 50% pain relief over six hours was 2.6 (95% confidence interval 2.2 to 3.2). There was no significant difference between the number of patients experiencing any adverse event on treatment compared with placebo. Weighted mean time to remedication was 7.6 hours for naproxen sodium 550 mg (206 patients) and 2.6 hours for placebo (205 patients). Four other trials used lower doses. CONCLUSION: A single oral dose of naproxen sodium 550 mg is an effective analgesic in the treatment of acute postoperative pain. A low incidence of adverse events was found, although these were not reported consistently.     

Human postural responses to different frequency vibrations of lower leg muscles

We analyzed human postural responses to muscle vibration applied at four different frequencies to lower leg muscles, the lateral gastrocnemius (GA) or tibialis anterior (TA) muscles. The muscle vibrations induced changes in postural orientation characterized by the center of pressure (CoP) on the force platform surface on which the subjects were standing. Unilateral vibratory stimulation of TA induced body leaning forward and in the direction of the stimulated leg. Unilateral vibration of GA muscles induced body tilting backwards and in the opposite direction of the stimulated leg. The time course of postural responses was similar and started within 1 s after the onset of vibration by a gradual body tilt. When a new slope of the body position was reached, oscillations of body alignment occurred. When the vibrations were discontinued, this was followed by rapid recovery of the initial body position. The relationship between the magnitude of the postural response and frequency of vibration differed between TA and GA. While the magnitude of postural responses to TA vibration increased approximately linearly in the 60-100 Hz range of vibration frequency, the magnitude of response to GA vibration increased linearly only at lower frequencies of 40-60 Hz. The direction of body tilt induced by muscle vibration did not depend on the vibration frequency.     

Elevated immunoreactive beta-endorphin level in ventricular fluid after analgesic electrical stimulation of posteromedial hypothalamus

Immunoreactive beta-endorphin (beta-EP) in the ventricular fluid of six carcinomatous patients was measured using a specific radioimmunoassay. The subjects were undergoing a surgical procedure for relief of chronic intractable pain. This procedure involved the focal stimulation and coagulation of the posteromedial hypothalamus. Samples of ventricular fluid were collected before and after the stimulation and serially after the coagulation. Prior to stimulation, beta-EP-like immunoreactivity (beta-EP-LI) was below 200 pg/ml. In all of the six patients with pain relief, electrical stimulation led to a marked increase in immunoreactive beta-EP. In three patients beta-EP levels remained high after electrical coagulation for 6-24 hrs. These results suggest that beta-EP-like material, released into the ventricular fluid, may contribute to the initial pain blockade that results from stimulation and coagulation of the posteromedial hypothalamus.     

Oral valdecoxib and injected parecoxib for acute postoperative pain: a quantitative systematic review

BACKGROUND: Clinical trials suggest that cyclo-oxygenase-2 specific inhibitors (coxibs) are an effective treatment for acute postoperative pain. The aims of this systematic review were to examine the evidence for oral valdecoxib and injected parecoxib, and quantify efficacy and adverse effects. METHODS: Information from randomized, double-blind studies in acute postoperative pain was sought. The area under the pain relief versus time curve over four to six hours was dichotomized using validated equations to derive the proportion of patients with treatment and placebo with at least 50% pain relief over four to six hours and calculate the number-needed-to-treat (NNT). Information on duration of analgesia and adverse events was also collected. RESULTS: The NNT for one patient to experience at least 50% relief over six hours following a single oral dose of valdecoxib 20 mg and 40 mg was 1.7 (1.4 to 2.0) and 1.6 (1.4 to 1.8) respectively. The NNT for one patient to have at least 50% relief over four to six hours with parecoxib 20 mg IV and 40 mg IV was 3.0 (2.3 to 4.1) and 2.3 (2.0 to 2.6) respectively. Mean time to remedication (weighted by trial size) was >24 hours with valdecoxib 40 mg, 8.7 hours with parecoxib 40 mg IV and 1.7 to 1.8 hours with placebo. There were no statistical differences between treatment and placebo for any adverse effect. CONCLUSION: Both oral valdecoxib and injected parecoxib are effective treatments for acute postoperative pain.     

First-dose analgesic effect of the cyclo-oxygenase-2 selective inhibitor lumiracoxib in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled comparison with celecoxib [NCT00267215]

Cyclo-oxygenase-2 selective inhibitors are frequently used to manage osteoarthritis. We compared the analgesic efficacy of the novel cyclo-oxygenase-2 selective inhibitor lumiracoxib (Prexige) versus placebo and celecoxib in patients with knee osteoarthritis. This seven day, double-blind, placebo and active comparator controlled, parallel group study included 364 patients aged > or = 50 years with moderate-to-severe symptomatic knee osteoarthritis. Patients received lumiracoxib 400 mg/day (four times the recommended chronic dose in osteoarthritis; n = 144), placebo (n = 75), or celecoxib 200 mg twice daily (n = 145). The primary variable was actual pain intensity difference (100 mm visual-analogue scale) between baseline and the mean of three hour and five hour assessments after the first dose. Actual pain intensity difference, average and worst pain, pain relief and functional status (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) were measured over seven days. Patients also completed a global evaluation of treatment effect at study end or premature discontinuation. For the primary variable, the superiority of lumiracoxib versus placebo, the noninferiority of lumiracoxib versus celecoxib, and the superiority of lumiracoxib versus celecoxib were assessed by closed test procedure adjusting for multiplicity, thereby maintaining the overall 5% significance level. In addition, celecoxib was assessed versus placebo in a predefined exploratory manner to assess trial sensitivity. Lumiracoxib provided better analgesia than placebo 3-5 hours after the first dose (P = 0.004) through to study end. The estimated difference between lumiracoxib and celecoxib 3-5 hours after the first dose was not significant (P = 0.185). Celecoxib was not significantly different from placebo in this analysis (P = 0.069). At study end 13.9% of lumiracoxib-treated patients reported complete pain relief versus 5.5% and 5.3% of celecoxib and placebo recipients, respectively. WOMAC total and subscales improved for both active treatments versus placebo except for difficulty in performing daily activities, for which celecoxib just failed to achieve significance (P = 0.056). In the patient's global evaluation of treatment effect, 58.1% of patients receiving lumiracoxib rated treatment as 'excellent' or 'good', versus 48.6% of celecoxib and 25.3% of placebo patients. Lumiracoxib was well tolerated. The overall incidence of adverse events was similar across treatment groups.     

Systematic review of dexketoprofen in acute and chronic pain

Background

Dexketoprofen, an NSAID used in the management of acute and chronic pains, is licensed in several countries but has not previously been the subjected of a systematic review. We used published and unpublished information from randomised clinical trials (RCTs) of dexketoprofen in painful conditions to assess evidence on efficacy and harm.

Methods

PubMed and Cochrane Central were searched for RCTs of dexketoprofen for pain of any aetiology. Reference lists of retrieved articles and reviews were also searched. Menarini Group produced copies of published and unpublished studies (clinical trial reports). Data were abstracted into a standard form. For studies reporting results of single dose administration, the number of patients with at least 50% pain relief was derived and used to calculate the relative benefit (RB) and number-needed-to-treat (NNT) for one patient to achieve at least 50% pain relief compared with placebo.

Results

Thirty-five trials were found in acute pain and chronic pain; 6,380 patients were included, 3,381 receiving dexketoprofen. Information from 16 trials (almost half the total patients) was obtained from clinical trial reports from previously unpublished trials or abstracts. Almost all of the trials were of short duration in acute conditions or recent onset pain. All 12 randomised trials that compared dexketoprofen (any dose) with placebo found dexketoprofen to be statistically superior. Five trials in postoperative pain yielded NNTs for 12.5 mg dexketoprofen of 3.5 (2.7 to 4.9), 25 mg dexketoprofen of 3.0 (2.4 to 3.9), and 50 mg dexketoprofen of 2.1 (1.5 to 3.5). In 29/30 active comparator trials, dexketoprofen at the dose used was at least equivalent in efficacy to comparator drugs. Adverse event withdrawal rates were low in postoperative pain and somewhat higher in trials of longer duration; no serious adverse events were reported.

Conclusion

Dexketoprofen was at least as effective as other NSAIDs and paracetamol/opioid combinations. While adverse event withdrawal was not different between dexketoprofen and comparator analgesics, the different conditions and comparators studies precluded any formal analysis. Exposure was limited, and no conclusions could be drawn about safety in terms of serious adverse events like gastrointestinal bleeding or cardiovascular events.     

Morphine: controlled trial of different methods of administration for postoperative pain relief.

Forty-five patients who had undergone major operations were given a slow intravenous injection of morphine sulphate (1 mg/ml saline) until their pain was relieved and were then randomly divided into three equal groups to receive different regimens of morphine sulphate over the next 72 hours. Patients in group A received 3.5 times the pain-relieving dose (28-63 mg, mean 36 mg) by continuous intravenous infusion; those in group B received the pain-relieving dose (90-160 mg, mean 110 mg) intramuscularly, four-hourly for the first 24 hours, six-hourly for the next 24 hours, and then eight and 20 hours later; and those in group C received the pain-relieving dose (80-280 mg, mean 140 mg) intramuscularly as required. Pain was assessed on a linear analogue scale and vital capacity and peak expiratory flow rate measured 12-hourly. The mean pain score was significantly lower and respiratory function significantly better in group A than in groups B and C. Only one patient (in group A) required extra morphine. Thus morphine administered by continuous intravenous infusion is superior to other regimens, giving better pain relief at a lower dosage.     

Effects of different vibration frequencies on spinal cord reflex circuits and thermoalgesic perception

Objectives:We studied the effect of different vibration frequencies on spinal cord excitability and heat pain perception. We hypothesized that the effects of vibration on spinal cord reflexes, and, also those on heat pain perception, depend on vibration frequency.Methods:In 9 healthy subjects, we applied vibration over the tibialis anterior muscle at three different frequencies (50, 150, or 250 Hz) on spinal cord reflex excitably, tested with the H reflex and the T wave in the soleus muscle, as well as on sensory and pain perception, tested by measuring warm perception (WT) and heat pain perception thresholds, (HPT) in sites rostral and caudal to vibration. Exams were carried out before, during, and after vibration.Results:The amplitude of the H reflex and T wave significantly decreased during vibration in comparison to baseline. Low frequencies (50 and 150Hz) induced greater reflex suppression than high frequency (250Hz). No significant changes were observed on WT and HPT.Conclusions:The effects of vibratory stimulation can be summarized as frequency-related suppression of the spinal cord excitability without an effect on warm and heat pain perception. The present results may help to design vibration-related interventions intended to diminish spinal cord reflex excitability in spastic patients.     

Quantification of gender specific thermal sensory and pain threshold before and after laser needle stimulation]

Quantitative thermal sensory and pain threshold testing (QST) was performed in 29 adult healthy volunteers (mean age 24.2 +/- 2.7 years; range: 18-29 years; 20 females, 9 males) using the Thermal Sensory Analyser TSA-II (Medoc Advanced Medical Systems, Ramat Yishai, Israel, and Minneapolis, Minnesota, USA) before and after laser needle acupuncture and placebo stimulation, respectively. Significant (p < or = 0,001; t-test) gender-specific differences were seen on cold pain threshold analysis. No significant changes in parameters of thermal sensory and pain thresholds were found before and after laser needle or placebo stimulation at acupuncture points for acute pain. However, a trend towards change in the median value of cold pain sensation after laser needle stimulation (p = 0.479; paired t-test; n.s.) was seen within the group of healthy females. The influence of stimulation of acupuncture points for chronic pain on the various parameters needs to be clarified in future studies.     

Adjustment of vibratory signals to ambient temperature in a host-searching parasitoid

Abstract.  Certain ichneumonid parasitoids (Hymenoptera) use self-produced vibrations transmitted on plant substrate, so-called vibrational sounding, to locate their immobile concealed pupal hosts. An ambient temperature dependency with higher frequencies and intensities at higher temperatures is postulated because signals are of myogenic origin. Here, temperature influence on vibratory signals is analysed in the temperate parasitoid Pimpla turionellae under different thermal conditions using plant-stem models to elicit host-searching behaviour. Signals are measured with laser Doppler vibrometry and analysed for time parameters and frequency components applying fast-Fourier transformations. The results reveal an unexpected effect of ambient temperature on signals produced by the female wasps. Although average values of time parameters (pulse trains, pulse train periods, inter pulse duration) are unchanged by ambient temperature, the frequency parameters show an inverse thermal effect. Within the temperature range tested (8–26 °C), decreasing temperature leads to significantly higher frequency and intensity of the self-produced vibrations in the temperate species. This inverse thermal effect may be explained by a temperature-coupled signal production in the frequency domain to compensate negative low-temperature effects on the mechanoreceptors by increased muscle activity. The option of heterothermy to produce signals reliably during vibrational sounding under low temperature is also discussed.     

Systematic review of the relative efficacy of non-steroidal anti-inflammatory drugs and opioids in the treatment of acute renal colic

Objective To examine the relative benefits and disadvantages of non-steroidal anti-inflammatory drugs (NSAIDs) and opioids for the management of acute renal colic.Data sources Cochrane Renal Group''s specialised register, Cochrane central register of controlled trials, Medline, Embase, and reference lists of retrieved articles.Review methods Randomised controlled trials comparing any opioid with any NSAID in acute renal colic if they reported any of the following outcomes: patient rated pain, time to pain relief, need for rescue analgesia, rate of recurrence of pain, and adverse events.Results 20 trials totalling 1613 participants were identified. Both NSAIDs and opioids led to clinically important reductions in patient reported pain scores. Pooled analysis of six trials showed a greater reduction in pain scores for patients treated with NSAIDs than with opioids. Patients treated with NSAIDs were significantly less likely to require rescue analgesia (relative risk 0.75, 95% confidence interval 0.61 to 0.93). Most trials showed a higher incidence of adverse events in patients treated with opioids. Compared with patients treated with opioids, those treated with NSAIDs had significantly less vomiting (0.35, 0.23 to 0.53). Pethidine was associated with a higher rate of vomiting.Conclusions Patients receiving NSAIDs achieve greater reductions in pain scores and are less likely to require further analgesia in the short term than those receiving opioids. Opioids, particularly pethidine, are associated with a higher rate of vomiting.     

Acute and residual neuromuscular effects of displacement in indirect vibratory stimulation

The aim of this study was to evaluate the effect of indirect vibratory stimulation on different magnitudes of displacement on acute and residual neuromuscular responses. Fifteen healthy volunteers were randomly submitted to 3 experimental sessions, with intervals of 5 to 7 days (5 maximal voluntary contractions - MVC, 12 s of duration each and 5 min of recovery) between sessions. To determine the residual responses, the volunteers performed a MVC before and after each treatment for 12 s, with a 5-minute recovery. The experimental sessions were composed of isometric actions without vibrations (CONTROL) and two sessions of isometric actions with the addition of vibrations at 20 Hz and 3 mm (Sinusoidal Vibration A) and 5 mm (Sinusoidal Vibration B). Before and after each of the experimental sessions, an isometric evaluation without vibrations was performed. For the acute effect, it was verified that the addition of vibrations induced a facilitatory effect on the explosive strength variables (p < .05), independent of the type of studied displacement in relation to the control treatment. In short, it was verified that the addition of vibration induced an acute facilitating effect on the explosive strength. However, the induced effect was not persistent (residual effect) for the explosive strength.     

Immediate and short-term pain relief by acute sciatic nerve press: a randomized controlled trial

Background

Despite much research, an immediately available, instantly effective and harmless pain relief technique has not been discovered. This study describes a new manipulation: a "2-minute sciatic nerve press", for rapid short-term relief of pain brought on by various dental and renal diseases.

Methods

This randomized, single-blind, placebo-controlled trial ran in three hospitals in Anhui Province, China, with an enrollment of 66 out of 111 solicited patients aged 16 to 74 years. Patients were recruited sequentially, by specific participating physicians at their clinic visits to three independent hospitals. The diseases in enrolled dental patients included dental caries, periodontal diseases and dental trauma. Renal diseases in recruits included kidney infections, stones and some other conditions. Patients were randomly assigned to receive the "2-minute sciatic nerve press" or the "placebo press". For the "2-minute sciatic nerve press", pressure was applied simultaneously to the sciatic nerves at the back of the thighs, using the fists while patients lay prone. For the "placebo press", pressure was applied simultaneously to a parallel spot on the front of the thighs, using the fists while patients lay supine. Each fist applied a pressure of 11 to 20 kg for 2 minutes, after which, patients arose to rate pain.

Results

The "2-minute sciatic nerve press" produced greater pain relief than the "placebo press". Within the first 10 minutes after sciatic pressure, immediate pain relief ratings averaged 66.4% (p < 0.001) for the dental patients, versus pain relief of 20% for the placebo press, and, 52.2% (p < 0.01) for the renal patients, versus relief of 14% for the placebo press, in median. The method worked excellently for dental caries and periodontal diseases, but poorly for dental trauma. Forty percent of renal patients with renal colic did not report any pain relief after the treatment.

Conclusion

Two minutes of pressure on both sciatic nerves can produce immediate significant conduction analgesia, providing a convenient, safe and powerful way to overcome clinical pain brought on by dental diseases and renal diseases for short term purposes.

Trial registration

ACTR 12606000439549     

Selective REM Sleep Deprivation Improves Expectation-Related Placebo Analgesia

The placebo effect is a neurobiological and psychophysiological process known to influence perceived pain relief. Optimization of placebo analgesia may contribute to the clinical efficacy and effectiveness of medication for acute and chronic pain management. We know that the placebo effect operates through two main mechanisms, expectations and learning, which is also influenced by sleep. Moreover, a recent study suggested that rapid eye movement (REM) sleep is associated with modulation of expectation-mediated placebo analgesia. We examined placebo analgesia following pharmacological REM sleep deprivation and we tested the hypothesis that relief expectations and placebo analgesia would be improved by experimental REM sleep deprivation in healthy volunteers. Following an adaptive night in a sleep laboratory, 26 healthy volunteers underwent classical experimental placebo analgesic conditioning in the evening combined with pharmacological REM sleep deprivation (clonidine: 13 volunteers or inert control pill: 13 volunteers). Medication was administered in a double-blind manner at bedtime, and placebo analgesia was tested in the morning. Results revealed that 1) placebo analgesia improved with REM sleep deprivation; 2) pain relief expectations did not differ between REM sleep deprivation and control groups; and 3) REM sleep moderated the relationship between pain relief expectations and placebo analgesia. These results support the putative role of REM sleep in modulating placebo analgesia. The mechanisms involved in these improvements in placebo analgesia and pain relief following selective REM sleep deprivation should be further investigated.     

Prospective double-blind comparison of buprenorphine and pethidine in ureteric colic.

In a double-blind prospective trial 26 consecutive patients with proved ureteric colic were allocated at random to receive 100 mg pethidine or 0.3 mg buprenorphine by intramuscular injection. Pain relief was assessed by standard linear analogue and ordered categories scales. The mean pain relief on the linear analogue scale was 3.80 +/- SEM 0.64 in patients receiving pethidine and 6.86 +/- 0.40 in those receiving buprenorphine (p less than 0.001). The corresponding values for mean pain relief in the ordered categories scale was 1.78 +/- 0.26 v 2.76 +/- 0.20 (p less than 0.01). These observations suggest that buprenorphine is superior to pethidine as analgesia in ureteric colic.     

Characterization of muscle spindle afferents in the adult mouse using an in vitro muscle-nerve preparation

We utilized an in vitro adult mouse extensor digitorum longus (EDL) nerve-attached preparation to characterize the responses of muscle spindle afferents to ramp-and-hold stretch and sinusoidal vibratory stimuli. Responses were measured at both room (24°C) and muscle body temperature (34°C). Muscle spindle afferent static firing frequencies increased linearly in response to increasing stretch lengths to accurately encode the magnitude of muscle stretch (tested at 2.5%, 5% and 7.5% of resting length [Lo]). Peak firing frequency increased with ramp speeds (20% Lo/sec, 40% Lo/sec, and 60% Lo/sec). As a population, muscle spindle afferents could entrain 1:1 to sinusoidal vibrations throughout the frequency (10-100 Hz) and amplitude ranges tested (5-100 μm). Most units preferentially entrained to vibration frequencies close to their baseline steady-state firing frequencies. Cooling the muscle to 24°C decreased baseline firing frequency and units correspondingly entrained to slower frequency vibrations. The ramp component of stretch generated dynamic firing responses. These responses and related measures of dynamic sensitivity were not able to categorize units as primary (group Ia) or secondary (group II) even when tested with more extreme length changes (10% Lo). We conclude that the population of spindle afferents combines to encode stretch in a smoothly graded manner over the physiological range of lengths and speeds tested. Overall, spindle afferent response properties were comparable to those seen in other species, supporting subsequent use of the mouse genetic model system for studies on spindle function and dysfunction in an isolated muscle-nerve preparation.     

Evaluation of Indomethacin by a Controlled,Cross-over Technique in 30 Patients with Ankylosing Spondylitis

A clinical evaluation of indomethacin employing a controlled, cross-over technique with an inert placebo was undertaken in 30 patients with ankylosing spondylitis. Patients were studied for the frequency and dose relationship of side effects and for the subjective response of morning stiffness, chronic spinal pain, acute exacerbations of pain and peripheral arthralgia. Objective evaluation assessed measured change in movements of the cervical and lumbar spines, in chest expansion and in the range of movement of involved peripheral joints.Evaluation of the results indicated that a significant number of patients experienced side effects in the form of headache and dizziness while receiving indomethacin in doses above 150 mg. per day. Many other side effects reported by the patients were not found to occur at a statistically significant level. The significance of pulmonary infections encountered in three patients was reviewed. Relief of chronic spinal pain and peripheral arthralgia occurred in 14 and 16 patients, respectively (p < 0.05). Relief of morning stiffness and acute exacerbations of pain, and increase in the range of movement of any of the segments of the spine or the involved peripheral joints were not significant (p > 0.05). Based on the results of this study, it is suggested that the role of indomethacin in the management of ankylosing spondylitis be re-evaluated and that the daily therapeutic dose of this drug which has been heretofore recommended be decreased.     

Parenteral dexamethasone for acute severe migraine headache: meta-analysis of randomised controlled trials for preventing recurrence

Objective To examine the effectiveness of parenteral corticosteroids for the relief of acute severe migraine headache and prevention of recurrent headaches.Design Meta-analysis.Data sources Electronic databases (Cochrane Central Register of Controlled Trials, Medline, Embase, LILACS, and CINAHL), conference proceedings, clinical practice guidelines, contacts with industry, and correspondence with authors.Selection criteria Randomised controlled trials in which corticosteroids (alone or combined with standard abortive therapy) were compared with placebo or any other standard treatment for acute migraine in adults.Review methods Two reviewers independently assessed relevance, inclusion, and study quality. Weighted mean differences and relative risks were calculated and are reported with 95% confidence intervals.Results From 666 potentially relevant abstracts, seven studies met the inclusion criteria. All included trials used standard abortive therapy and subsequently compared single dose parenteral dexamethasone with placebo, examining pain relief and recurrence of headache within 72 hours. Dexamethasone and placebo provided similar acute pain reduction (weighted mean difference 0.37, 95% confidence interval −0.20 to 0.94). Dexamethasone was, however, more effective than placebo in reducing recurrence rates (relative risk 0.74, 95% confidence interval 0.60 to 0.90). Side effect profiles between dexamethasone and placebo groups were similar.Conclusion When added to standard abortive therapy for migraine headache, single dose parenteral dexamethasone is associated with a 26% relative reduction in headache recurrence (number needed to treat=9) within 72 hours.