Double-blind comparison of meclofenamate sodium with codeine and placebo for the pain of episiotomy

Meclofenamate sodium, a nonsteroidal anti-inflammatory agent, was compared at two dose levels (100 mg and 200 mg) with codeine (60 mg) and placebo in a double-blind, randomized study of 218 women after normal vaginal delivery. The purpose was to determine the analgesic efficacy and safety of meclofenamate sodium for the short-term treatment of acute episiotomy pain. Meclofenamate sodium was significantly better than placebo in most measures of pain relief and reduction of pain intensity. The 100-mg dose of meclofenamate sodium was significantly better than codeine in relieving pain. Adverse experiences with the study medications were minimal (6.4%). Patients receiving codeine reported more side effects than did those receiving either dose of meclofenamate sodium. Meclofenamate sodium is a safe, effective analgesic for acute episiotomy pain.     

Thermographic Findings in Cranio-Facial Pain

This work assesses the differences in the thermographic findings in the craniofacial and neck areas between normal individuals and patients with craniofacial pain or headache, and investigates the influence of muscle contraction on such findings. Thermographic records were taken in 10 healthy subjects and 47 patients suffering from craniofacial pain or headache of different kinds. In the patients with painful episodes the record was taken between attacks. In all the normal subjects and in 19 patients lateral thermograms were also taken during and after maximal tooth clenching for three minutes. The majority of the patients, as compared to the normal group, showed some thermal alterations and asymmetry. Such alterations seem to be due both to vascular instability and muscle contraction: these two factors may be variably superimposed in the different conditions. In patients with cluster headache or chronic paroxysmal hemicrania the presence on the symptomatic side of a cold spot along the supraorbital area and/or the inner orbital canthus, was a constant finding. We conclude that thermography is useful as an additional diagnostic means in patients with head and face pain, and that the clenching test may increase the amount of information provided.     

Analgesic efficacy of morphine applied topically to painful ulcers

The analgesic effects of morphine applied topically to painful ulcers was assessed in a randomized, double-blind, placebo-controlled, crossover pilot study of five patients with painful sacral sores. Patients were treated for two days with either 10 mg morphine sulfate or placebo (water for injection) applied topically to the ulcer. After a two-day wash-out period, patients were crossed over for a further two days of the alternative treatment. Patients were asked to rate analgesia using a visual analogue scale (VAS) and to document any local or systemic adverse effects. All patients reported lower VAS scores with morphine compared to placebo and no local or systemic adverse events attributable to morphine were noted by either patients or nursing staff. This pilot study suggests that morphine applied topically is an effective method of producing local analgesia, well tolerated by patients, and not associated with systemic adverse effects.     

Comparison of meclofenamate sodium with buffered aspirin and placebo for the relief of postoperative dental pain

The analgesic effect of meclofenamate sodium at two dose levels (100 mg and 200 mg) was compared with the effects of buffered aspirin (600 mg) and placebo in a double-blind, randomized study of 105 dental outpatients with acute pain following third-molar extraction. Meclofenamate sodium at either dose level was significantly superior to both buffered aspirin and placebo, resulting in significantly greater relief of pain. All four treatments were well tolerated, and side effects were minimal. Meclofenamate sodium is a safe, highly effective analgesic for the relief of acute pain.     

Usefulness of low-level laser for control of painful stomatitis in patients with hand-foot-and-mouth disease

OBJECTIVE: The aim of this study was to evaluate the usefulness of low-level laser therapy (LLLT) for the control of painful stomatitis in patients with hand-foot-and-mouth disease (HFMD). BACKGROUND DATA: LLLT has been successfully applied to various painful oral mucosal diseases, although there have been few reports on LLLT for HFMD patients. MATERIALS AND METHODS: Through a randomized double-blind placebo controlled trial, the painful period of HFMD stomatitis was compared between the LLLT group (n=11) and the placebo LLLT one (n=9), which had similar clinical backgrounds. The LLLT parameters supplied were as follows: wavelength of 830 nm, power of 30 mW, frequency of 30 Hz, and energy output of 1.1 J/cm2. Acceptability and safety of the treatment were also evaluated. RESULTS: The painful period was shorter in the LLLT group (4.0 +/- 1.3 days) than in the placebo LLLT one (6.7 +/- 1.6 days) with a statistically significant difference (p<0.005). The treatment was judged acceptable for 90.0% (18 of 20) of patients. No adverse events were observed in any cases. CONCLUSION: LLLT is a useful method to control HFMD stomatitis by shortening the painful period, with its high acceptability and lack of adverse events.     

Diffuse noxious inhibitory control evoked by tonic craniofacial pain in humans

Tonic pain in one body segment can inhibit the perception of pain in another body segment. This phenomenon is mediated by diffuse noxious inhibitory controls (DNIC), and its efficacy in craniofacial regions is investigated in this study. A compressive device that evoked a tonic, moderate/severe, headache‐like, conditioning pain (～8/10 on a visual analogue scale) was applied for 15 min. Eleven males participated in the study. Pressure pain threshold (PPT) and pressure pain tolerance (PPTol) at multiple heterosegmental body sites (right masseter, splenius capitis, second intermediate phalange, brachioradialis and tibialis anterior) were measured before, during and at multiple time points (5, 20 and 35 min) after the termination of the conditioning pain. PPTs and PPTols were compared within participants across two experimental sessions; one that included painful conditioning stimulation, and a separate control session on a different day. Painful conditioning increased PPT significantly during pain over the masseter (p <0.05) and over the tibialis anterior (p <0.01). PPTol was unchanged. In the period after the painful conditioning stimulation PPT was depressed compared to control. This study shows that pain evoked from the craniofacial region evokes DNIC‐like mechanisms on segmental as well as heterosegmental sites.     

Transdermal clonidine compared to placebo in painful diabetic neuropathy using a two-stage ‘enriched enrollment’ design

Because a variety of mechanisms may generate pain in neuropathic pain syndromes, conventional clinical trial methods may fail to identify some potentially useful drugs; a drug affecting just a single mechanism may work in too few patients to yield a statistically significant result for the trial. To test a previous clinical observation that approximately one-quarter of patients with painful diabetic neuropathy appear responsive to clonidine, we conducted a formal clinical trial of transdermal clonidine in painful diabetic neuropathy patients using a 2-stage enriched enrollment design. In the first stage (study I), 41 patients with painful diabetic neuropathy completed a randomized, 3-period crossover comparison of transdermal clonidine (titrated from 0.1 to 0.3 mg/day) to placebo patches. Twelve apparent responders from study I were entered into the ‘enriched enrollment’ second stage (study II), consisting of an additional 4 double-blind, randomized, 1-week treatment periods with transdermal clonidine and placebo. Study I showed that in the overall group of 41 patients, pain intensity differed little during clonidine and placebo treatment. In study II, however, the 12 apparent responders from study I had 20% less pain with clonidine than placebo (95% confidence interval (CI): 4–35% pain reduction; P = 0.015), confirming that their pain was responsive to clonidine. None of the 3 consistent clonidine responders who were tested with the -adrenergic blocker phentolamine had relief of pain, suggesting that clonidine's pain relief is not mediated by a decrease in sympathetic outflow. A post-hoc analysis of many variables suggested that patients who described their pain as sharp and shooting may have a greater likelihood of responding to clonidine. The results of this study support the hypothesis that there is a subset of patients with painful diabetic neuropathy who benefit from systemic clonidine administration and illustrate the value of an enriched enrollment technique in analgesic trials.     

Hypalgesic efficacy of acupuncture on experimental pain in man. Comparison of laser acupuncture and needle acupuncture

The analgesic effect of acupuncture on cutaneous heat stimuli of 43 degrees C has been evaluated in a controlled experimental study with healthy, informed volunteers. Laser acupuncture was administered to 39 probationers using a helium-neon laser under double-blind conditions. The point Hegu (L.I.4) and Jianqian (Extra.) on both sides were each irradiated for 1 min. Forty probationers were needled with stainless steel needles in the point Hegu (L.I.4) on both sides under single-blind conditions. Pain threshold was measured in terms of the time (in msec) that the probationers needed to perceive the cutaneous heat stimulus of 43 degrees C. The painful stimulus was generated by a computer-controlled standardized procedure. The Wilcoxon test was used for the statistical evaluation. Laser acupuncture did not change the pain threshold. Needle acupuncture did, however, increase the pain threshold compared with the initial value (alpha = 0.1%). The difference compared with the control group, where a placebo point was needled, was also significant (alpha = 5%). This controlled experimental study proves the analgesic effect of needle acupuncture on painful heat stimuli. Laser acupuncture had no effect on pain threshold in this study.     

Effects of doxepin on perception of laboratory-induced pain in man.

Beneficial effects have been observed in University of Washington Pain Clinic patients treated with tricyclic antidepressants, but such effects occur much earlier than predicted mood elevation. A laboratory investigation of pain perception was employed to test the hypothesis that doxepin, a tricyclic antidepressant, has analgesic properties. Healthy, normal volunteers were tested over a 4-week period during which they repeatedly performed Sensory Decision Theory tasks while undergoing painful dental stimulation. Doxepin and a placebo were administered after baseline measurement for 4 weeks under double blind conditions. No significant changes due to drug administration were observed in detection threshold or sensory sensitivity indices, but response bias against reporting the stimuli as painful changed dramatically after subjects began ingesting capsules. This effect was evident in both drug and placebo groups, and it was maintained across repeated weeks of testing. These observations suggest that the instructions given patients when the drug is administered have a profound effect on pain report.     

Treatment of chronic painful diabetic neuropathy with isosorbide dinitrate spray: a double-blind placebo-controlled cross-over study

OBJECTIVE: Considerable evidence implicates impaired nitric oxide (NO) generation in the pathogenesis of diabetic neuropathic pain. We therefore conducted a pilot study to examine the effects of isosorbide dinitrate (ISDN), a NO donor with local vasodilating properties, in spray form in the management of chronic neuropathic pain. RESEARCH DESIGN AND METHODS: The study was of double-blind, randomized, placebo-controlled, and two-period cross-over design. After a 2-week run-in period, 22 diabetic patients (13 men, 20 with type 2 diabetes, age [mean +/- SE] 63.7 +/- 1.8 years, duration of diabetes 9.1 +/- 1.5 years, duration of painful neuropathy 2.6 +/- 0.4 years) were randomized to receive ISDN or placebo sprays for 4 weeks, exchanging their treatment for a further 4 weeks after a 2-week wash-out period. The patients administered the spray to both feet before bedtime. Biweekly pain and other sensory symptoms were assessed using a visual analog scale (VAS) and the Lickert scale, respectively. RESULTS: ISDN spray reduced overall neuropathic pain (P = 0.02) and burning sensation (P = 0.006). No treatment difference was observed with other sensory modalities (hot/cold sensation, tingling, numbness, hyperesthesia, and jabbing-like sensation). At study completion, 11 patients (50%) reported benefit and wished to continue using the ISDN spray, 4 (18%) preferred the placebo spray, and the remaining 7 (32%) were undecided. CONCLUSIONS: ISDN spray offers an alternative and effective pharmacological option in relieving overall pain and burning sensation in the management of painful diabetic neuropathy. The potential of ISDN spray in alleviating other specific sensory symptoms associated with diabetic peripheral neuropathy merits further study.     

Postoperative pain relief: a double-blind comparison of dezocine, butorphanol, and placebo

The safety and efficacy of single intramuscular doses of dezocine (10 or 15 mg) were compared with butorphanol (2 mg) and placebo in 157 patients with moderate to severe postoperative pain. A verbal pain intensity scale, an analog pain intensity scale, and a verbal pain relief scale were used to record the patients' subjective assessments. The results of this study indicate that a single 10 or 15 mg intramuscular injection of dezocine is safe and more effective than placebo for four to six hours, respectively, in the treatment of moderate to severe postoperative pain (P less than .05). During the first hour of treatment the pain relief afforded by 2 mg of butorphanol was significantly greater than that afforded by 10 mg of dezocine (P less than .05), but both doses of dezocine provided long-lasting relief. The scores on all three efficacy scales were highest with the 15 mg dose of dezocine after the first hour, while the 10 mg dose of dezocine and butorphanol were compared during this period. Nausea and vomiting were the most commonly reported side effects; injection site reactions were reported more frequently in the butorphanol group.     

Effects of auricular transcutaneous electrical nerve stimulation on experimental pain threshold

This study was conducted to examine the effects of high intensity transcutaneous electrical nerve stimulation at auricular acupuncture points on experimental pain threshold. Forty-five healthy adult male and female subjects were assigned randomly to one of two treatment groups or to a control group. Subjects in the two treatment groups received high intensity TENS to either appropriate or inappropriate (placebo) acupuncture points on one ear. Experimental pain threshold at the ipsilateral wrist was determined with a painful electrical stimulus before and after ear stimulation. Only the group receiving stimulation of appropriate ear acupuncture points exhibited a significant increase (p less than .01) in experimental pain threshold after ear stimulation. The comparable placebo and control groups, again, did not exhibit significant pretest-posttest differences in experimental pain threshold. The results suggest that, if applied accurately, auricular TENS can increase pain threshold. Further research is needed to assess the effects of this technique on patient groups.     

Sodium valproate for painful diabetic neuropathy: a randomized double-blind placebo-controlled study

BACKGROUND: Various drugs are effective in the management of painful diabetic neuropathy, but none is completely satisfactory. We previously found sodium valproate to be effective and safe in a short-term study. AIM: To test the effectiveness and safety of sodium valproate in the management of painful diabetic neuropathy over 3 months. DESIGN: Randomized double-blind placebo-controlled study. METHODS: Consecutive attending patients with type 2 diabetes mellitus with painful neuropathy were asked to participate in the trial: 48 agreed. Five were excluded: three with HbA(1c) > 11, one with too low a pain level and one who withdrew consent. The remaining 43 were given either drug (group A) or placebo (group B). Each patient was assessed clinically. Quantitative assessment of pain was done by McGill Pain Questionnaire, Visual Analogue Score and Present Pain Intensity, at the beginning of the study, after 1 month and after 3 months. Motor and sensory nerve conduction velocities were measured initially and after 3 months. Liver function tests and other adverse drug-related effects were assessed periodically. RESULTS: Of the 43 patients, four dropped out: one in group A and three in group B. There was significant improvement in pain score in group A, compared to group B, at 3 months (p < 0.001). Changes in electrophysiological data were not significant. The drug was well-tolerated by all patients, except one, who had raised serum AST and ALT levels after 1 month of treatment, and whose treatment was discontinued. DISCUSSION: Sodium valproate is well-tolerated, and provides significant subjective improvement in painful diabetic neuropathy.     

Clinical Science (42)

Intravenous clodronate in the treatment of reflex sympathetic dystrophy syndrome: a randomized, double blind, placebo‐controlled study. (Istituto Ortopedico Gaetano Pini, Milan, Italy) J Rheumatol 2000;27:1477–1483. This study evaluated the efficacy of intravenous (IV) clodronate in patients with reflex sympathetic dystrophy syndrome (RSDS) and assessed the urinary excretion of type 1 collagen crosslinked N‐telopeptide (NTx) before and after treatment. Thirty‐two patients with RSDS were randomized to receive either IV Clodronate 300 mg daily for 10 consecutive days or placebo. Forty days later, the placebo treated patients received the clodronate treatment. Outcome measures included as a primary endpoint the visual analog scale of pain (VAS, range 0–100); secondary endpoints were a clinical global assessment (CGA, range 0–3) and an efficacy verbal score (EVS, range 0–3). Clinical and biochemical assessments were performed before the treatment, 40 (T40), 90 (T90), and 180 (T180) days later. At T40 the 15 patients randomized to clodronate treatment showed significant decreases of VAS and CGA (P = 0.002, P = 0.001, respectively). Compared with the placebo group (17 patients), significant differences were found in all clinical variables. A further clinical improvement was observed throughout the study. Pooling the results of all 32 patients after clodronate treatment, at T180 the overall percentage decrease of VAS was 9.32 ± 15.6% with 30 patients significantly improved or asymptomatic. Significant inverse correlations between baseline NTx values and decreases of VAS were found at T90 (P = 0.03) and T180 (P = 0.01). No adverse events related to treatment occurred. Conclude that a 10‐day IV clodronate course is better than placebo and effective in the treatment of RSDS. NTx seems to be a predictive factor for clodronate efficacy. Comment by Susan Anderson, MD. This is a randomized double blind placbo controlled study to evaluate the efficacy of intravenous clodronate in patients with reflex sympathetic dystrophy syndrome (RSDS) or complex regional pain syndrome type I. It is also to assess the urinary excretion of type I collogen crosslink N‐telopeptide (NTx) before and after the treatment. Thirty‐two patients with complex regional pain syndrome type I were randomized to receive either a placebo or IV clodronate 300mg daily for 10 consecutive days. At the end of 40 days, the placebo group was then treated with the clodronate. The primary endpoint measures with the visual analog scale (VAS, range 0–100) and a secondary endpoint was the clinical global assessment (CGA, range 0–3), and an efficacy vocal score (EVS, range 0–3). In addition, the patient had clinical and biochemical assessments performed before the treatment at 40 days, at 90 days, and at 180 days later. The purpose of the study was valued at the efficacy of the IV clodronate in pain relief. The second purpose was to evaluate the possibility of using NTx as a predicting factor for evaluating complex regional pain syndrome type I or the clodranate efficacy. On day 40, 15 patients that were randomized to the clodronate treatment showed significant decreases in their VAS and CGA when compared with the placebo group with 17 patients. In addition, the patients who had originally received placebo infusions showed decreased VAS and CGA scores after 40 days of treatment with the clodronate when compared to their VAS and CGA scores after placebo. At 180 days, the patients continued to show significant improvement or were asymptomatic. Bisphosphonates have been proposed since 1988 for the treatment of CRPS type I. The most frequently used is pamidronate, which is given intravenously showing varied results. The pamidronate did not seem to be well tolerated. Alendronate is also given intravenously demonstrating good efficacy. It, however, has a high relapse rate. Clodronate was chosen for this study because it was efficacious in treatment of various painful skeletal disorders and was more tolerable and safe than the pamidronate. The length of the time of the study was chosen to be 10 consecutive days so that it followed the study with successful use of pamidronate. These results suggest that a 10‐day IV clodronate course is better than placebo and is an effective complex regional pain syndrome type I treatment that may induce prompt and long lasting improvement. This study also attempted to demonstrate NTx as a predictive factor for clodranate efficacy. While NTx has shown to be a specific and sensitive marker of bone resorption, in this study, they found a low association between high NTx values and the complex regional pain syndrome type I. This finding could weaken the relationship between NTx baseline values and the responsiveness to clodronate treatment. It should be noted, however, that there were significant immerse correlations found between the baseline NTx values and in the pain improvement measured on the percentage change of VAS at 90 days and 180 days. Therefore, while significant inverse correlations may have been determined, and the NTx may be a promising tool, it is not yet possible to determine the predictive rolls of NTx as a marker.     

Etodolac, aspirin, and placebo in patients with rheumatoid arthritis: a 12-week study

Etodolac, aspirin, and placebo were evaluated for efficacy and safety in 18 patients with adult-onset, active rheumatoid arthritis. This was a 12-week, double-blind, parallel-group study divided into drug titration and maintenance periods and preceded by a washout period of up to two weeks. The mean daily maintenance doses of etodolac and aspirin were 394 mg and 4,414 mg, respectively. Etodolac was significantly (P less than or equal to 0.05) more effective than placebo in five of ten clinical variables of efficacy: number of painful joints, number of swollen joints, pain intensity, erythrocyte sedimentation rate, and patients' overall assessments. Aspirin was significantly more effective than placebo in only two assessments: number of painful joints and pain intensity. One patient on etodolac, two patients on aspirin, and four patients on placebo had to be withdrawn from the trial because of insufficient therapeutic response. One patient in the placebo group was withdrawn from the study because of a pruritic rash. Mild to moderate gastrointestinal complaints occurred in all three treatment groups: in three patients taking etodolac, three taking aspirin, and two taking placebo.     

Local steroid injections for tennis elbow: does the pain get worse before it gets better?: Results from a randomized controlled trial

OBJECTIVES: To compare the early effects of local corticosteroid injection, naproxen, and placebo as treatments for tennis elbow in primary care. Specifically, to find out whether the extra pain reduction experienced by patients who are given the steroid injection in the short-term would be realized within the first 5 days of treatment and to attempt to assess how much extra pain may be associated with the injection initially. METHODS: A randomized controlled trial carried out in 23 family practices in the United Kingdom. A total of 164 patients aged 18 to 70 years presenting with a new episode of tennis elbow were recruited and invited to keep a daily record of their pain intensity and medication use over the first 5 days of randomized treatment using a "diary." RESULTS: On day 1, pain scores were higher in the injection group compared with the naproxen group and placebo group, and the injection group was also taking more painkillers. By day 4, the converse was true, pain scores were significantly lower in the injection group than the other 2 groups, and patients given an injection were less likely to be taking painkillers than those in the placebo group. DISCUSSION: Steroid injection was associated with an increase in reported pain for the first 24 hours of treatment, but the therapeutic benefits compared with naproxen and placebo were evident 3 to 4 days after the start of treatment.     

Comparison of the analgesic efficacy of rofecoxib and enteric-coated diclofenac sodium in the treatment of postoperative dental pain: a randomized,placebo-controlled clinical trial

BACKGROUND: Rofecoxib is a selective cyclooxygenase-2 inhibitor indicated for the treatment of acute pain, with similar analgesic efficacy to ibuprofen and naproxen sodium. Diclofenac sodium is the most commonly prescribed nonsteroidal anti-inflammatory drug worldwide; it is effective for the treatment of pain as well as the signs and symptoms associated with the painful conditions of osteoarthritis and rheumatoid arthritis. OBJECTIVE: The aim of this study was to compare the analgesic efficacy and tolerability of a single dose of rofecoxib 50 mg, 3 doses of enteric-coated diclofenac sodium 50 mg, and placebo over 8-hour and 24-hour periods in patients with moderate to severe pain after oral surgery. METHODS: In this double-blind, placebo- and active comparator-controlled, parallel-group study, patients experiencing moderate to severe pain after the surgical extraction of > or = 2 third molars were randomized to receive a single dose of rofecoxib 50 mg, 3 doses of enteric-coated diclofenac sodium 50 mg (50 mg given every 8 hours), or placebo. Patients rated pain intensity, pain relief, and global assessments at prespecified times throughout the 24-hour period after initial dosing. Overall analgesic efficacy was determined by total pain relief over 8 hours (TOPAR8) and 24 hours (TOPAR24) and patient global assessments at 8 and 24 hours. Onset of analgesic effect was determined by using the 2-stopwatch method for confirmed perceptible pain relief. Peak analgesic effect was the maximum pain relief attained during the first 8 hours. The duration of analgesic effect was determined by median time to rescue analgesia use. RESULTS: A total of 305 patients were randomized to treatment: 121 received rofecoxib, 121 received diclofenac sodium, and 63 received placebo. The baseline demographics were similar among the groups. Overall, 61.3% experienced moderate pain and 38.7% experienced severe pain; 53.1% were female; and the mean age was 23.4 years. The overall analgesic efficacy, as assessed by TOPAR8, of a single dose of rofecoxib 50 mg was significantly greater than a single dose of enteric-coated diclofenac sodium 50 mg (20.5 vs 8.2) and placebo (20.5 vs 5.9). Patient global assessment at 8 hours was also significantly better for rofecoxib compared with enteric-coated diclofenac sodium and placebo. TOPAR24 was significantly greater for a single dose of rofecoxib 50 mg compared with 3 doses of enteric-coated diclofenac sodium 50 mg (64.1 vs 25.1) and placebo (64.1 vs 19.2). At 24 hours, the patient global assessment for rofecoxib was significantly better than that achieved with enteric-coated diclofenac sodium and placebo. The onset of analgesic effect was significantly more rapid for rofecoxib than for enteric-coated diclofenac sodium and placebo (median times: 31 minutes, >4 hours, and >4 hours, respectively). The peak analgesic effect was significantly greater for rofecoxib compared with enteric-coated diclofenac sodium (3.2 vs 1.5) and placebo (3.2 vs 1.1). The duration of analgesia was significantly longer for rofecoxib than enteric-coated diclofenac sodium (median times: >24 hours vs 1 hour and 37 minutes) and placebo (>24 hours vs 1 hour and 37 minutes). Enteric-coated diclofenac sodium was numerically greater than placebo for the key end points measuring overall efficacy (total pain relief and patient global assessment), but diclofenac sodium did not provide as much analgesic effect as expected for a drug effective for pain, osteoarthritis, and rheumatoid arthritis and did not differ significantly from placebo. Overall, both rofecoxib and enteric-coated diclofenac sodium were generally well tolerated, although the rofecoxib group had a significantly lower incidence of clinical and drug-related adverse events than the enteric-coated diclofenac sodium group. CONCLUSIONS: A single 50-mg dose of rofecoxib provided greater overall analgesic efficacy over 8 hours, more rapid onset of analgesia, greater maximum analgesic effect, and longer duration of effect than a single 50-mg dose of enteric-coated diclofenac sodium in patients with moderate to severe pain associated with oral surgery. Compared with 3 doses of enteric-coated diclofenac sodium 50 mg (50 mg every 8 hours), a single dose of rofecoxib 50 mg provided greater overall analgesic efficacy over 24 hours.     

Nitrous oxide analgesia in humans: acute and chronic tolerance

Electrical tooth stimulation was used to investigate whether humans develop tolerance to nitrous oxide (N(2)O) analgesia within a single administration as well as over repeated administrations. In a double-blind cross-over experiment, 77 subjects received a 40-min administration of 38% N(2)O at one session and placebo gas at the other. The sessions were separated by 1 week and the order of gas administration was counterbalanced. Acute analgesic tolerance developed for pain threshold but not for detection threshold. There was no evidence of a hyperalgesic rebound effect following cessation of the N(2)O administration. In a second double-blind experiment, 64 subjects received both 30-min of placebo gas and 30-min of 35% N(2)O, separated by a 35-min gas wash-out period, during each of five sessions. Sensory thresholds were assessed prior to drug or placebo administration (baseline) and between 7-12 and 25-30 min of gas administration. A control group of 16 subjects received only placebo gas at these five sessions. During a sixth session, the experimental procedures were similar to the previous sessions except that the control group received N(2)O for the first time and the experimental group was sub-divided to test for conditioned drug effects. For both detection and pain threshold measures, acute tolerance developed during the initial N(2)O exposure and chronic tolerance developed over repeated administrations. Although chronic tolerance developed, a test for Pavlovian drug conditioning found no evidence of conditioned effects on sensory thresholds. In conclusion, acute and chronic tolerance develop to N(2)O's analgesic effects in humans.     

Diode laser in cervical myofascial pain: a double-blind study versus placebo

We present a double-blind trial in which a pulsed infrared beam was compared with a placebo in the treatment of myofascial pain in the cervical region. The patients were submitted to 12 sessions on alternate days to a total energy dose of 5 J each. At each session, the four most painful muscular trigger points and five bilateral homometameric acupuncture points were irradiated. Those in the placebo group submitted to the same number of sessions following an identical procedure, the only difference being that the laser apparatus was nonoperational. Pain was monitored using the Italian version of the McGill pain questionnaire and the Scott-Huskisson visual analogue scale. The results show a pain attenuation in the treated group and a statistically significant difference between the two groups of patients, both at the end of therapy and at the 3-month follow-up examination.