Ibuprofen Versus Aspirin and Placebo in the Treatment of Muscle Contraction Headache

SYNOPSIS
One hundred eight patients with muscle contraction headaches completed a double-blind, randomized, parallel trial in which they took either ibuprofen 400 mg, ibuprofen 800 mg, a spirin 650 mg, or placebo for four successive headaches. Acetaminophen was allowed as a rescue analgesic. Intensity of headache pain was recorded pretreatment and three hours posttreatment. A Pain Intensity Difference (PID) score was calculated from the difference. Patients on ibuprofen (both doses) and aspirin had significantly lower pain scores and higher PID scores at three-hour follow-up than did patients on placebo. Physician's global assessment indicated that both doses of ibuprofen were significantly superior to placebo; aspirin was not. The highest number of side effects occurred with aspirin (26 complaints), followed by placebo (11), ibuprofen 400 mg (3), and ibuprofen 800 mg (2); all were minor. These results suggest that, for the treatment of muscle contraction headache, ibuprofen is significantly more effective than placebo and at least as effective as aspirin.     

Analgesic effects of adenosine in syndrome X are counteracted by theophylline: a double-blind placebo-controlled study

It has been proposed that adenosine mediates ischaemic pain in humans. Patients with cardiac Syndrome X are hypersensitive to potential pain stimuli, including adenosine. On the other hand, recent findings suggest that low-dose adenosine infusion may have analgesic effects. Our aim was to test two hypotheses: (1) that the analgesic effect of adenosine is peripheral in origin, and (2) that part of the hypersensitivity to pain of patients with cardiac Syndrome X results from a disturbed mechanism of adenosine analgesia. A total of 12 female Syndrome X patients and eight healthy age-matched female controls were studied in a randomized, double-blind and placebo-controlled study. Adenosine (70 microg/min) or placebo was infused into the forearm via an intra-arterial catheter. After 15 min of infusion, a tourniquet on the upper arm was inflated to 225 mmHg to ensure arterial occlusion. The patient then carried out dynamic handgrip work at 60 Hz. Pain or discomfort in the forearm was estimated continuously according to the Borg CR-10 scale. After the first test, theophylline was infused for 10 min intravenously at a dose of 5 mg/kg body weight. The ischaemic forearm test was then repeated. On a second occasion, the procedure was repeated with the opposite treatment (adenosine/placebo). Only six of 12 Syndrome X patients completed the protocol because of pain during the catheterization procedure or an inability to establish an intra-arterial line. The time to onset of pain in the working, ischaemic forearm was greater for subjects treated with adenosine than for those treated with placebo, both in those Syndrome X patients who tolerated catheterization (49+/-27 s compared with 32+/-18 s; P<0.03) and in healthy controls (40+/-19 s compared with 16+/-8 s; P<0.02). The time to maximum pain, limiting ischaemic work, was also greater with adenosine pretreatment both in Syndrome X patients (137+/-28 s compared with 106+/-28 s; P<0.03) and in healthy controls (109+/-31 compared with 82+/-18 s; P<0.01). After infusion of theophylline there was no difference between adenosine and placebo in either group. Intra-arterially infused adenosine had similar peripheral analgesic effects on experimentally induced muscular ischaemia in those female Syndrome X patients who tolerated intra-arterial catheterization and in healthy controls. Thus adenosine analgesia is counteracted by theophylline, suggesting that the effect is mediated by membrane-bound peripheral adenosine receptors.     

Ibuprofen plus caffeine in the treatment of tension-type headache

BACKGROUND: The effectiveness of caffeine as an adjuvant to ibuprofen has been documented in investigations of acute pain. Our objectives were to assess this agent in the treatment of tension-type headache and to establish clinical trial methods capable of assessing this agent in comparison with various tension headache treatments. Stopwatch technology was used for measurement techniques. METHODS: A randomized, double-blind, parallel, multicenter, single-dose, placebo- and active-controlled study included 301 subjects diagnosed with tension-type headache. Treatment groups included ibuprofen and caffeine, ibuprofen alone, caffeine alone, or placebo. Subjects measured onset of relief (both time to first perceptible relief and time to meaningful relief) after taking a single oral dose of their assigned medication. Pain intensity and pain relief were rated over a 6-hour study period. Overall evaluation was made on completion of all other ratings. RESULTS: Ibuprofen and caffeine administered together provided significantly greater analgesic activity than ibuprofen alone, caffeine alone, and placebo. Ibuprofen and caffeine administered together demonstrated significantly shorter times to meaningful improvement in headache relief than ibuprofen or placebo; significantly greater total analgesia than ibuprofen alone, caffeine alone, or placebo; and significantly greater peak relief than ibuprofen alone, caffeine alone, or placebo. Significantly more subjects obtained meaningful headache relief with ibuprofen and caffeine administered together than with ibuprofen alone or placebo. More patients reported complete headache relief with ibuprofen and caffeine administered together than with ibuprofen alone, caffeine alone, or placebo. Ibuprofen and caffeine administered together was rated significantly better by patients than either ibuprofen alone, caffeine alone, or placebo. No subjects ended participation in the study early because of adverse events. CONCLUSIONS: Sensitive methods have been introduced to assess differences in analgesia among over-the-counter analgesic agents in relieving tension-type headache pain. A double-blind study with this method suggests that ibuprofen and caffeine administered together provides greater analgesic effectiveness than either component alone.     

A Single-Blind,Placebo Run-in Study of Duloxetine for Activity-Limiting Osteoarthritis Pain

Osteoarthritis pain is a significant problem for our aging population. Antidepressants that are serotonin-norepinephrine reuptake inhibitors are effective for other forms of chronic pain and may provide a new treatment option for osteoarthritis pain. We performed a single-blind, placebo run-in trial of 60 to 90 mg of duloxetine in 25 subjects with activity-limiting osteoarthritis pain. Each subject received 2 weeks of placebo followed by 10 weeks of duloxetine. The primary outcome was reduction in average pain intensity between 2 and 12 weeks for subjects completing the trial. Average pain on the Brief Pain Inventory (BPI) was 5.7 at baseline, 4.8 after the 2-week placebo run-in, and 3.5 at 12 weeks for the 17 patients completing the trial (28% decrease between 2 and 12 weeks, P = .122). Eight of 15 study completers who had nonmissing BPI results (53%) reported at least 30% pain reduction between weeks 2 and 12. The Western Ontario McMaster Osteoarthritis Index (WOMAC) pain score at baseline was 2.3, 1.8 after 2 weeks, and 1.3 after 12 weeks (30% decrease between 2 and 12 weeks, P = .018). Ten of 17 patients (59%) reported at least 30% pain relief between weeks 2 and 12 on the WOMAC. Significant improvements in self-reported physical and role function were reported but observed physical function did not improve.PerspectiveDuloxetine did not significantly reduce pain intensity on the BPI but did improve pain intensity and self-reported function on the WOMAC. Duloxetine warrants further investigation as a novel treatment for osteoarthritis pain.     

Caffeine attenuates delayed-onset muscle pain and force loss following eccentric exercise.

This double-blind, placebo-controlled, repeated-measures experiment examined the effects of a 5 mg . kg(-1) body weight dose of caffeine on delayed-onset muscle pain intensity and force loss in response to 64 eccentric actions of the dominant quadriceps induced by electrical stimulation. Low caffeine-consuming college-aged females (n = 9) ingested caffeine or placebo 24 and 48 hours following electrically stimulated eccentric exercise of the quadriceps. One hour after ingestion, maximal voluntary isometric contractions (MVIC) and submaximal voluntary eccentric actions were used to determine force loss during activation of damaged quadriceps and whether caffeine attenuates muscle pain intensity. Pain intensity was measured using a 0 to 100 visual analog scale. Caffeine produced a large (12.7 raw visual analog scale [VAS] units; -48%; Cohen's d effect size = -0.88), statistically significant hypoalgesia during the MVIC (t = -2.52; df = 8; P = .036). The reduction in pain scores during submaximal voluntary eccentric movements was smaller (7.8 raw VAS units; -26%, d = -0.34), as was the increase in MVIC force (4.4%; d = 0.13). PERSPECTIVE: Eccentric exercise occurs when skeletal muscles produce force while being lengthened. For example, the biceps brachii muscles act eccentrically when a cup of coffee is lowered from the mouth to a tabletop. This experiment found that caffeine (equal to approximately 2 cups of brewed coffee) could produce a large reduction in pain resulting from eccentric exercise-induced, delayed-onset muscle injury. This finding may improve the quality of life of individuals who experience skeletal muscle pain after engaging in unaccustomed, eccentrically biased exercise.     

Head Pain as a Result of Experimental Ischemic Exercise of the Temporalis Muscle

SYNOPSIS
Reports indicate that ischemia relative to cranial muscle activity accompanies muscle contraction headache and jaw claudication. The purpose of this study was to experimentally create ischemia in exercising temporalis muscle in order to determine if this combination would produce head pain. Ten subjects were studied during each of three experimental conditions: temporalis muscle ischemia, rhythmic temporalis muscle exercise, and both ischemia and temporalis muscle exercise combined. Ischemia was produced by a scalp sphygmomanometer and verified by Doppler ultrasonic flowmetry of the superficial temporal artery. Temporalis muscle exercise was produced by gum chewing at 60 strokes/min using 30% of maximum electromyographic (EMG) activity. The time to onset of pain and the time to reach pain tolerance were measured. Pain, using either exercise or ischemia alone developed in a median time of 27 minutes and was seldom located in the temporal area. Pain, using both exercise and ischemia, developed in a median time of three minutes and was predominantly located in the temporal area. Both onset and tolerance times were shorter in the combined protocol when compared to ischemia or exercise alone (r<.001). Tenderness to palpation was observed in the temporal muscle following the combined procedure but not following the individual procedures. The results support the view that ischemic temporal muscle activity can produce head pain.     

Immediate effects on electromyographic activity and pressure pain thresholds after a cervical manipulation in mechanical neck pain: a randomized controlled trial

Objective

The purpose of this study was to identify the immediate effects of a manipulation of C5/C6 level on electromyography (EMG) of the deltoid muscle and in pressure pain thresholds (PPTs) in patients with mechanical neck pain.

Methods

Thirty-seven subjects with mechanical neck pain were randomly divided into 2 groups: manipulative group, which received a cervical spine manipulation targeted to C5/C6 segment, and a control group, which did not receive any procedure. Outcomes were EMG data of the deltoid muscle (rest, isometric contraction for 5 or 30 seconds, and isotonic contraction) and PPT over upper trapezius and deltoid muscles and C5 spinous process. They were assessed before and 5 minutes after treatment by a blinded assessor. A 3-way repeated-measures analysis of variance was used to examine the effects of the manipulation.

Results

A significant group time interaction for MF at the beginning of isometric contraction for 30 seconds (F = 7.957, P = .006) was also found: the manipulative group experienced a greater increase in MF at the beginning of the isometric contraction than did the control group. A significant group time interaction was also found for root mean square during isometric contraction for 30 seconds (P = .003); however, changes were small. Patients within the manipulative group experienced an increase on PPT over the deltoid (P = .010) and C5 spinous process (P = .025), but not over upper trapezius (P = .776).

Conclusions

Manipulation at C5/C6 level in the study participants seemed to increase EMG amplitude signal and fatigue resistance in a nonspinal (deltoid) muscle innervated by the same segment in patients with mechanical neck pain. However, these changes were relative small. An increase on PPT over those tissues innervated by the manipulated segment was also found after the manipulative procedure.     

Ketamine reduces muscle pain, temporal summation, and referred pain in fibromyalgia patients

Central mechanisms related to referred muscle pain and temporal summation of muscular nociceptive activity are facilitated in fibromyalgia syndrome (FMS) patients. The present study assessed the effects of an NMDA-antagonist (ketamine) on these central mechanisms. FMS patients received either i.v. placebo or ketamine (0.3 mg/kg, Ketalar((R))50% decrease in pain intensity at rest by active drug on two consecutive VAS assessments). Fifteen out of 17 ketamine-responders were included in the second part of the study. Before and after ketamine or placebo, experimental local and referred pain was induced by intramuscular (i.m.) infusion of hypertonic saline (0.7 ml, 5%) into the tibialis anterior (TA) muscle. The saline-induced pain intensity was assessed on an electronic VAS, and the distribution of pain drawn by the subject. In addition, the pain threshold (PT) to i.m. electrical stimulation was determined for single stimulus and five repeated (2 Hz, temporal summation) stimuli. The pressure PT of the TA muscle was determined, and the pressure PT and pressure pain tolerance threshold were determined at three bilaterally located tenderpoints (knee, epicondyle, and mid upper trapezius). VAS scores of pain at rest were progressively reduced during ketamine infusion compared with placebo infusion. Pain intensity (area under the VAS curve) to the post-drug infusion of hypertonic saline was reduced by ketamine (-18. 4+/-0.3% of pre-drug VAS area) compared with placebo (29.9+/-18.8%, P<0.02). Local and referred pain areas were reduced by ketamine (-12. 0+/-14.6% of pre-drug pain areas) compared with placebo (126.3+/-83. 2%, P<0.03). Ketamine had no significant effect on the PT to single i.m. electrical stimulation. However, the span between the PT to single and repeated i.m. stimuli was significantly decreased by the ketamine (-42.3+/-15.0% of pre-drug PT) compared with placebo (50. 5+/-49.2%, P<0.03) indicating a predominant effect on temporal summation. Mean pressure pain tolerance from the three paired tenderpoints was increased by ketamine (16.6+/-6.2% of pre-drug thresholds) compared with placebo (-2.3+/-4.9%, P<0.009). The pressure PT at the TA muscle was increased after ketamine (42.4+/-9. 2% of pre-drug PT) compared with placebo (7.0+/-6.6%, P<0.011). The present study showed that mechanisms involved in referred pain, temporal summation, muscular hyperalgesia, and muscle pain at rest were attenuated by the NMDA-antagonist in FMS patients. It suggested a link between central hyperexcitability and the mechanisms for facilitated referred pain and temporal summation in a sub-group of the fibromyalgia syndrome patients. Whether this is specific for FMS patients or a general phenomena in painful musculoskeletal disorders is not known.     

beta-Endorphin modulates adenosine provoked chest pain in men, but not in women-a comparison between patients with ischemic heart disease and healthy volunteers

INTRODUCTION: Increasing evidence suggests the existence of sex differences in pain perception. Adenosine, an early messenger for myocardial ischemia induces angina pectorislike symptoms in healthy volunteers and in patients with ischemic heart disease. AIMS: To study whether sex influences adenosine-provoked chest pain and the analgesic effect of the opioid receptor agonist beta-endorphin. MATERIALS AND METHODS: Twenty patients (10 male and 10 female) with significant coronary artery disease and 20 healthy volunteers (10 male and 10 female) were studied. Both the hand algometer and Borg CR-10 scale were used to estimate chest pain. Chest pain was provoked double-blind by injections of placebo, 1/3, 2/3, 3/3 of maximal tolerable dose of adenosine twice in randomized order. This procedure was repeated after bolus injection of beta-endorphin followed by infusion and repeated a third time after bolus injection of naloxone 0.8 mg. Central chest pain and physiologic responses were quantified using hemodynamic and psychophysical methods. RESULTS: Pain estimate by hand algometer and the Borg CR-10 scale was correlated (r=0.77, P<0.001). Both sexes reported a dose-dependent increase of adenosine-provoked chest pain with no differences for maximum tolerable dose of adenosine per kilogram. beta-Endorphin administration lowered adenosine-provoked pain in both male patients and male healthy volunteers (P=0.02) but not in women. Naloxone tended to increase the pain perception in male patients (P=0.052) and male healthy volunteers (P=0.054), but did not have any significant effect on pain modalities in female. CONCLUSIONS: In conclusion, women were resistant to beta-endorphin modulation of adenosine-provoked chest pain. In male patients, beta-endorphin induced analgesia.     

NGF-evoked sensitization of muscle fascia nociceptors in humans

Nerve growth factor (NGF) induces local hyperalgesia for a few days after intramuscular injection, but longer-lasting muscle pain upon systemic administration. As the muscle fascia is densely innervated by free nerve endings, we hypothesized a lasting sensitization of fascia nociceptors by NGF. We administered 1 μg NGF (dissolved in 100 μL saline) ultrasound-guided to the fascia of the Musculus erector spinae muscle at the lumbar level of 14 male volunteers and assessed hypersensitivity after 6 hours, and 1, 3, 7, 14, and 21 days. Pain upon mechanical stimuli (constant pressure and dynamic impact), upon exercise and electrically induced M. erector spinae contraction, and upon injection of 100 μL phosphate buffer pH4 (at day 7 and 14 only) to the fascia of both NGF- and saline-treated muscles, was investigated. Injections into the muscle fascia did not cause acute pain. Local heat pain thresholds were unchanged following NGF and saline (control) administration. NGF evoked a lasting (days 1-7) and significant reduction of pressure pain, pressure thresholds, exercise-evoked muscle pain, and hyperalgesia to impact stimuli (12 m/s). Pain upon injected protons was significantly elevated (P<0.04) for 2 weeks. NGF induced a sensitization of the muscle fascia to mechanical and chemical stimuli lasting for up to 2 weeks. As nociceptors in the fascia appear to be particularly prone to sensitization, they may contribute to acute or chronic muscle pain.     

Slowing in Peak-Alpha Frequency Recorded After Experimentally-Induced Muscle Pain is not Significantly Different Between High and Low Pain-Sensitive Subjects

Peak alpha frequency (PAF) reduces during cutaneous pain, but no studies have investigated PAF during movement-related muscle pain. Whether high-pain sensitive (HPS) individuals exhibit a more pronounced PAF response to pain than low-pain sensitive (LPS) individuals is unclear. As a pain model, twenty-four participants received nerve growth factor injections into a wrist extensor muscle at Day 0, Day 2, and Day 4. At Day 4, a subgroup of twelve participants also undertook eccentric wrist exercise to induce additional pain. Pain numerical rating scale (NRS) scores and electroencephalography were recorded at Day 0 (before injection), Day 4, and Day 6 for 3 minutes (eyes closed) with wrist at rest (Resting-state) and extension (Contraction-state). The average pain NRS scores in contraction-state across Days were used to divide participants into HPS (NRS-scores≥2) and LPS groups. PAF was calculated by frequency decomposition of electroencephalographic recordings. Compared with Day 0, contraction NRS-scores only increased in HPS-group at Day 4 and Day 6 (P < .001). PAF in Contraction-state decreased in both groups at Day 6 compared with Day 0 (P = .011). Across days, HPS-group showed faster PAF than LPS-group during Resting-state and Contraction-state (P < .04). Average pain NRS-scores across days during Contraction-states correlated with PAF at Day 0 (P = .012). Pain NRS-scores were associated with PAF during Contraction-state at Day 4 and Day 6 (P < .05).PerspectivePAF was slowed during long-lasting movement-related pain in both groups, suggesting a widespread change in cortical excitability independent of the pain sensitivity. Moreover, HPS individuals showed faster PAF than LPS individuals during muscle pain, which may reflect a different cognitive, emotional, or attentional response to muscle pain among individuals.     

Efficacy of combination intravenous lidocaine and dexamethasone on propofol injection pain: a randomized, double-blind, prospective study in adult Korean surgical patients

BACKGROUND: Pain on injection is a common adverse effect with propofol used for general anesthesia. OBJECTIVES: The aims of this study were to evaluate the analgesic effect of dexamethasone during propofol injection and investigate whether a combination of dexamethasone and lidocaine produced additional analgesic efficacy compared with either treatment alone. METHODS: In a double-blind, prospective trial, patients scheduled to undergo elective plastic surgery were randomized to receive lidocaine 20 mg, dexamethasone 6 mg, combination lidocaine 20 mg and dexamethasone 6 mg, or normal saline with venous occlusion for 1 minute, followed by administration of 25% of the total calculated dose of propofol (2.5 mg/kg) into a dorsal hand vein. Pain intensity and incidence were evaluated during a 10-second pause before the induction of anesthesia, using a 4-point verbal rating scale (0=none, 1=mild, 2=moderate, 3=severe); a score of 1 to 3 was counted as pain. Patients were monitored hourly for 24 hours postsurgery by a blinded investigator for adverse effects at the injection site (eg, pain, edema, wheal, flare response). RESULTS: A total of 140 (35 per group) Korean patients (91 women, 49 men; mean [SD] age, 47 [14] years; mean [SD] height, 162 [8] cm; and mean [SD] body weight, 60 [8] kg) completed the study. Demographic variables were similar among groups. With respect to pain intensity, mean pain score was significantly less in the combination group than in the lidocaine or dexamethasone groups (P<0.01, respectively), although the median pain scores for all groups were 0. The incidence of pain associated with propofol injection was reduced significantly in the combination group compared with the lidocaine or dexamethasone group (0% vs 34.3% and 37.1%, respectively; both, P<0.01). One patient (in the combination group) complained of perineal itching immediately following injection; however, this subsided within a few seconds and did not require any intervention. No other adverse effects at the injection site were observed in any patient in the 24 hours post surgery. CONCLUSION: Combination lidocaine 20 mg and dexamethasone 6 mg, with venous occlusion for 1 minute, was more effective than lidocaine 20 mg or dexamethasone 6 mg alone for pain control during propofol injection in these Korean patients.     

Nicotine and caffeine intake in complex regional pain syndrome

{\it Objective:} Nicotine and caffeine are vasoconstrictors. Complex regional pain syndrome (CRPS) is defined to involve disproportionate pain and autonomic dysfunction [1]. The objectives of this study were to identify the prevalence of smoking and caffeine intake in CRPS, to explore the relationship of pain intensity with smoking and caffeine consumption, and to explore the relationship of pain intensity, anxiety and disability among CRPS patients who smoke, use caffeine, or both. {\it Design:} One hundred eleven patients, with CRPS type I or II, from two academic rehabilitation pain clinics were reviewed. Data were collected retrospectively by reviewing CRPS patients' self-reported pain level using visual analogue scales (VAS), Beck Depression Inventory (BDI), Pain Disability Index (PDI), and Pain Anxiety Symptoms Scale (PASS). Status of daily smoking and caffeine consumption were also recorded. {\it Results:} Smoking prevalence among CRPS was significant higher than the national average (p < 0.001). There were no significant relationships between the perceived pain level and either daily smoking, daily caffeine intake, or both (p > 0.430). In patients with CRPS I higher PASS scores were positively associated with dichotomous use of smoking and caffeine (p < 0.05). The PASS scores among patients with CRPS~II were not available for analysis. {\it Conclusions:} The smoking prevalence was higher than the national average among patients with CRPS I and II. Among patients with CRPS~I smoking and caffeine consumption were greater in those who reported more pain-related anxiety, but did not influence pain intensity. The clinical implications of these findings will be discussed.     

Experimental pain by ischaemic contractions compared with pain by intramuscular infusions of adenosine and hypertonic saline.

Deep tissue pain can be related to reduced muscle blood flow, which comprises the metabolic demand under muscle work. The tissues and receptors involved in nociception after ischaemic muscle contractions are not known. The concentration of adenosine is increased after ischaemic contractions and might act as an algesic substance. In 15 subjects, adenosine, hypertonic saline (algesic), and isotonic mannitol (placebo) were infused into the tibialis anterior muscle and compared with the pain caused by ischaemic contractions. The muscle pain intensity (visual analogue scale; VAS), distribution, and quality were assessed. Pressure pain thresholds were recorded to assess the deep tissue sensitivity. Adenosine did not induce more pain than the placebo. The maximal VAS score after hypertonic saline and ischaemic contractions was higher compared with adenosine/placebo infusions. The duration and area of pain were significantly increased after hypertonic saline infusions compared with ischaemic contractions. Higher scores on the McGill pain questionnaire were given to the "stabbing", "burning", "heavy", and "exhausting" word categories after ischaemic contractions, and "cramping" was rated higher during hypertonic saline-induced muscle pain compared with ischaemic contractions. During hypertonic saline infusions, the pressure pain threshold was decreased compared with before and immediately after the pain had vanished. The present study shows that pharmacological levels of adenosine in skeletal muscle did not induce pain. Excitation of muscle nociceptors by hypertonic saline evoked hyperalgesia, larger areas of pain, and a different quality of pain compared with ischaemic contractions, suggesting that the pain after ischaemic contractions is mediated by other populations of nociceptors in muscle and/or other tissues than excited by hypertonic saline.     

Muscle activation after supervised exercises in patients with rotator tendinosis

OBJECTIVE: To determine whether pain reduction induced by supervised exercises over several months results in increased maximal force and muscle activation. DESIGN: Before-after trial. PARTICIPANTS: Ten patients with unilateral rotator tendinosis and more than 3 months' duration of pain. INTERVENTION: Supervised exercises for 3 to 6 months. OUTCOME MEASURES: Maximal abduction force, muscle activation by surface electromyogram (EMG), and pain were assessed during brief maximal voluntary isometric contractions (MVC) before and after fatigue. EMG and pain were assessed during sustained submaximal contraction, performed with the shoulder 45 degrees abducted. The testing protocol was performed before and after supervised exercises. RESULTS: In the afflicted shoulder, resting pain was reduced after supervised exercises and no longer differed from the unafflicted side. The increase in pain during contraction was almost the same before and after treatment. MVC force increased, but significant side differences remained. EMG increased for trapezius and deltoid muscles in both afflicted and unafflicted arms. Fatigue development and recovery was unaltered by the exercise regimen. CONCLUSIONS: Pain reduction after supervised exercises was associated with an improved MVC force, but the side difference in maximal force generation was maintained. Muscle activity during maximal contraction increased in both the afflicted and unafflicted sides.     

Effect of caffeine on perceptions of leg muscle pain during moderate intensity cycling exercise.

This double-blind, within-subjects experiment examined the effect of ingesting a large dose of caffeine on perceptions of leg muscle pain during moderate intensity cycling exercise. Low-caffeine-consuming college-aged males (n = 16) ingested either caffeine (10 mg x kg(-1) body weight) or placebo and 1 hour later completed 30 minutes of moderate intensity cycling exercise (60% VO(2peak)). The order of drug administration was counter-balanced. Perceptions of leg muscle pain as well as work rate, heart rate, and oxygen uptake (VO(2)) were recorded during exercise. Leg muscle pain ratings were significantly and moderately reduced after a high dose of caffeine. This observation suggests that prior reports showing caffeine improves endurance exercise performance might be partially explained by caffeine's hypoalgesic properties. It also suggests that moderate intensity cycling exercise has promise as a useful experimental model for the study of naturally occurring muscle pain.     

Onset of action of a lozenge containing flurbiprofen 8.75 mg: A randomized,double-blind,placebo-controlled trial with a new method for measuring onset of analgesic activity

A new onset-of-action model was utilized to distinguish the pharmacologic activity of flurbiprofen 8.75 mg delivered in a lozenge from the demulcent effect of the lozenge base. In a randomized, double-blind, placebo-controlled trial, patients with sore throat rated pain on a Sore Throat Pain Intensity Scale before taking one flurbiprofen or placebo lozenge and at frequent (2-minute) intervals over the first hour after treatment. Further ratings of the Sore Throat Pain Intensity Scale and other patient-reported outcomes (difficulty swallowing, swollen throat, pain relief) were obtained at varying intervals over 6 hours. Onset of pharmacologic activity was defined as the median time of first perceived pain reduction if a patient reported clinically meaningful (at least moderate) relief. The conventional method of comparing mean treatment responses at each time point was also implemented. Demulcent action was detected at the first 2-minute assessment. By the new method, 102 flurbiprofen-treated patients were identified as first perceiving pain relief at 12 minutes, compared with >120 minutes by 102 patients using placebo (P < 0.001). By the conventional method, mean percentage pain reduction for flurbiprofen 8.75 mg was first significantly differentiated from placebo at 26 minutes (P < 0.05). Efficacy of flurbiprofen lozenge was demonstrated for 3.5-4 hours on the 4 patient-reported outcomes (all P < 0.05 compared with placebo). There were no serious adverse events. This patient-centered onset-of-action model identifies the initiation of pain relief in patients who are definite drug responders, here demonstrating that a flurbiprofen 8.75-mg lozenge provides early relief of sore throat.     

Effects of caffeine as an adjuvant to morphine in advanced cancer patients. A randomized, double-blind, placebo-controlled, crossover study

Psychomotor abnormalities are one of the complications of opioid therapy in advanced cancer patients. Caffeine has potential properties to counteract the central effects of morphine. Twelve patients receiving stable doses of slow release morphine with adequate pain relief were scheduled for this double-blind placebo-controlled crossover trial. The treatment consisted of an intravenous dose of 1/6 of the daily morphine dose, using an intravenous/oral conversion ratio of 1:3. The dose calculated was administered in 5 minutes. Patients were randomly divided to received in a double-blind manner an infusion of 200 mg of caffeine or saline solution intravenously over one hour. A crossover took place after 2-3 days. Patients were assessed immediately before the infusion and once at the end (one hour after). Each assessment included pain, nausea, confusion, and drowsiness intensity. Psychomotor tests, including tapping speed with 10-30 seconds trials, arithmetic tests, memory for digits, and visual memory were also performed. Caffeine infusion induced a significant decrease in pain intensity (from 25.3 to 16.3, p =0.003), but this was no different from the placebo. Caffeine increased both tapping speed tests (p = 0.041 and 0.010, respectively) in comparison with placebo treatment. No other significant differences were found in the other parameters examined. Caffeine showed a partial effect on the cognitive performance of advanced cancer patients on chronic morphine treatment who received a bolus of intravenous morphine. Further studies are necessary to evaluate whether higher doses of caffeine may be more effective and to establish the role of tolerance to caffeine in this group of patients.     

A Longitudinal Randomized Trial of the Effect of Consistent Pain Management for Infant Vaccinations on Future Vaccination Distress

The objective was to determine if consistent pain management during vaccine injections has a beneficial effect on future infant pain reactivity. This was a multicenter, longitudinal, double-blind, double-dummy, add-on, randomized controlled trial. Healthy infants were randomized to 1 of 4 add-on pain management regimens for all vaccinations in the first year of life: 1) placebo control (standard care), 2) parent video education about infant soothing (video), 3) video and oral sucrose solution (sucrose), 4) video and sucrose and topical liposomal lidocaine (lidocaine). At 15-month vaccinations, all active pain interventions were administered (video and sucrose and lidocaine); however, individuals remained blinded to the original treatments given. Pain at 15 months was evaluated during 3 procedure phases (baseline, needle injection, and recovery) by a researcher unaware of group allocation using a validated measure, the Modified Behavioural Pain Scale (range, 0–10). Altogether, 352 infants participated; characteristics did not differ among groups (P > .05). Pain scores did not differ among groups during baseline (P = .642), needle injection (P = .739), or recovery (P = .750) phases. In conclusion, there was no evidence of a long-term benefit of consistent use of pain interventions in the first year of life on future infant pain responsivity at 15-month vaccinations.

Ginger (Zingiber officinale) Reduces Muscle Pain Caused by Eccentric Exercise

Ginger has been shown to exert anti-inflammatory effects in rodents, but its effect on human muscle pain is uncertain. Heat treatment of ginger has been suggested to enhance its hypoalgesic effects. The purpose of this study was to examine the effects of 11 days of raw (study 1) and heat-treated (study 2) ginger supplementation on muscle pain. Study 1 and 2 were identical double-blind, placebo controlled, randomized experiments with 34 and 40 volunteers, respectively. Participants consumed 2 grams of either raw (study 1) or heated (study 2) ginger or placebo for 11 consecutive days. Participants performed 18 eccentric actions of the elbow flexors to induce pain and inflammation. Pain intensity, perceived effort, plasma prostaglandin E₂, arm volume, range-of-motion and isometric strength were assessed prior to and for 3 days after exercise. Results Raw (25%, –.78 SD, P = .041) and heat-treated (23%, –.57 SD, P = .049) ginger resulted in similar pain reductions 24 hours after eccentric exercise compared to placebo. Smaller effects were noted between both types of ginger and placebo on other measures. Daily supplementation with ginger reduced muscle pain caused by eccentric exercise, and this effect was not enhanced by heat treating the ginger.PerspectiveThis study demonstrates that daily consumption of raw and heat-treated ginger resulted in moderate-to-large reductions in muscle pain following exercise-induced muscle injury. Our findings agree with those showing hypoalgesic effects of ginger in osteoarthritis patients and further demonstrate ginger's effectiveness as a pain reliever.