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Analgesic activity of spiradoline mesylate (U-62,066E), a kappa opioid agonist in mice.

The present study was undertaken to evaluate the analgesic potency of spiradoline mesylate, a k(kappa) opioid agonist, in comparison with that of morphine, by hot plate, tail-pinch and acetic acid-induced writhing assay. The ED50 values of spiradoline in hot plate, tail-pinch and acetic acid-induced writhing assay were 0.46, 0.26 and 0.20 mg/kg, respectively. The analgesic potency of spiradoline was 1.5-7.0 times higher than that of morphine. Repeated treatment with spiradoline as well as morphine developed tolerance to the analgesic effect in hot plate assay. In mice developed tolerance to one analgesic, response to the other analgesic did not alter compared to saline-treated mice. Single administration of spiradoline (1.5 and 3 mg/kg, s.c.) did not inhibit morphine-induced analgesia. These results suggest that spiradoline has more potent analgesic activity than morphine, presumably mediated through stimulation of receptors different from morphine.

Analgesia↗

The analgesic activity of a clonidine analog. The formamidine, U-47,476A.

A compound structurally related to clonidine, N,N-dimethyl-N'-(2,4, 6-trimethyl phenyl)formamidine hydrochloride (U-47,476A), was evaluated for analgesic activity; it produced a significant analgesia in mice and rats in several analgesiometric procedures. The analgesic potency varied considerably with different analgesiometric tests, with ED50s ranging from 0.4 mg/kg for writhing in mice induced by hydrochloric acid to greater than 30 mg/kg for the tail-flick test in rats. Although the potency was less than that of clonidine, it was still in the range of pentazocine. Then U-47,476A was further examined to determine whether the analgesic effect was mediated by alpha-adrenergic mechanisms and accompanied by hypotension and sedation, similar to that produced by clonidine. The drug U-47,476A failed to lower significantly blood pressure in rats given 10 and 30 mg/kg subcutaneously, suggesting a possible separation of the hypotensive and analgesic properties of this compound. The locomotor activity of mice was unaltered after 0.5 mg/kg of U-47,476A; however, a significant decrease in activity was observed after the administration of 5 mg/kg. The effect of U-47,476A on locomotor activity in the mouse was significantly less than that for an approximately equipotent analgesic dose of clonidine. The analgesic effect of U-47,476A was antagonized by yohimbine, but not by reserpine, naloxone or phentolamine, Thus, the attenuation of the response to noxious stimuli by U-47,476A is mediated by alpha 2-adrenoceptors and not by opioid receptors or presynaptic monoaminergic mechanisms, similar to clonidine-induced analgesia.

Amidines↗

Analgesic and acute central nervous system side effects of the intravenously administered enkephalinase inhibitor SCH 32615.

The analgesic and acute central nervous system (CNS) side effect potential of the enkephalinase inhibitor SCH 32615 (N-[L-(1-carboxy-2-phenyl)ethyl]-L-phenyl-alanine-beta-alanine) were evaluated after IV administration to mice, rats and squirrel monkeys. In mice, SCH 32615 caused dose-related suppression of acetic acid-induced writhing (minimal effective dose, MED = 3 mg/kg IV). In rats, SCH 32615 produced dose-related increases in the response latencies in the yeast inflamed-paw test (MED = 10 mg/kg IV). In squirrel monkeys, using a new hot-water bath tail-flick test, SCH 32615 significantly prolonged the escape latencies (MED = 100 mg/kg IV). These results in primates are the first data showing an analgesic action of an enkephalinase inhibitor in a reflex model of pain. When measured for its CNS side effect potential, SCH 32615 had no significant effects in rats (up to 100 times its analgesically active doses) or in monkeys (up to three times). In the mouse, at doses 100 times its minimal effective dose, SCH 32615 produced brief convulsions; these lasted only a minute, resolved quickly, and did not cause lethality. In contrast, in rats and squirrel monkeys, the standard opioid analgesic morphine produced profound CNS side effects; this was particularly notable in monkeys, in which morphine's maximal analgesic effects were associated with near lethal respiratory depression. These data demonstrate that SCH 32615 produces selective analgesic actions and that its acute side effect liability is less than that seen with a clinically used standard.

Acetates↗

Opioid analgesics and rates of fatal drug poisoning in the United States.

OBJECTIVE: To determine whether the variability in rate of sale of prescription opioid analgesics is related to the variability in rates of drug poisoning mortality among states in the United States in 2002. METHODS: Drug poisoning deaths were defined as unintentional deaths or those of undetermined intent whose underlying cause was coded to "narcotics" (X42) or "other and unspecified" drugs (X44) in the National Vital Statistics System. Per capita sales of ten opioid analgesics from the Drug Enforcement Administration and combined sales in morphine equivalents were correlated with drug poisoning mortality rates by state using multivariate linear regression. Regression coefficients between mortality rates and sales rates were adjusted for race (percent white, percent black) and age (percent aged 24 years or younger, and percent aged 65 years and older). RESULTS: There was over a ten-fold variability in sales of some opioid analgesics. Combined sales ranged 3.7-fold, from 218 mg per person in South Dakota to 798 mg per person in Maine. Drug poisoning mortality varied 7.9-fold, from 1.6/100,000 in Iowa to 12.4/100,000 in New Mexico. Drug poisoning mortality correlated most strongly with non-OxyContin oxycodone (r=0.73, p<0.0001), total oxycodone (r=0.68, p<0.0001), and total methadone (r=0.66, p<0.0001) in the multivariate analysis. A scatterplot demonstrated a linear relationship between total opioid analgesic sales and drug poisoning mortality. CONCLUSIONS: The extent of opioid analgesics use varies widely in the United States. Variation in the availability of opioid analgesics is related to the spatial distribution of drug poisoning mortality by state.

Analgesics, Opioid↗

Nonnarcotic analgesics and hypertension.

In 2004, individuals in the United States spent >$2.5 billion on over-the-counter (OTC) nonsteroidal anti-inflammatory drugs (NSAIDs) and filled >100 million NSAID prescriptions. The most commonly used OTC analgesics include aspirin, acetaminophen, and nonaspirin NSAIDs. Nonnarcotic analgesics are generally considered safe when used as directed but do have the potential to increase blood pressure in patients with hypertension treated with antihypertensives. This is important because hypertension alone has been correlated with an increased risk of cardiovascular disease or stroke. Small increases in blood pressure in patients with hypertension also have been shown to increase cardiovascular morbidity and mortality. Therefore, when nonnarcotic analgesics are taken by patients with hypertension, there may be important implications. This review explores the potential connection among analgesic agents, blood pressure, and hypertension, and discusses possible mechanisms by which analgesics might cause increases in blood pressure. This is followed by a summary of data on the relation between analgesics and blood pressure from both observational and randomized trials.

Acetaminophen↗

Major increases in opioid analgesic abuse in the United States: concerns and strategies.

The problem of abuse of and addiction to opioid analgesics has emerged as a major issue for the United States in the past decade and has worsened over the past few years. The increases in abuse of these opioids appear to reflect, in part, changes in medication prescribing practices, changes in drug formulations as well as relatively easy access via the internet. Though the use of opioid analgesics for the treatment of acute pain appears to be generally benign, long-term administration of opioids has been associated with clinically meaningful rates of abuse or addiction. Important areas of research to help with the problem of opioid analgesic abuse include the identification of clinical practices that minimize the risks of addiction, the development of guidelines for early detection and management of addiction, the development of opioid analgesics that minimize the risks for abuse, and the development of safe and effective non-opioid analgesics. With high rates of abuse of opiate analgesics among teenagers in the United States, a particularly urgent priority is the investigation of best practices for treating pain in adolescents as well as the development of prevention strategies to reduce diversion and abuse.

Analgesics, Opioid↗

Endogenous opioids are involved in morphine and dipyrone analgesic potentiation in the tail flick test in rats.

The combined administration of low doses of opiates with non-steroidal anti-inflammatory drugs can produce additive or supra-additive analgesic effects while reducing unwanted side effects. We have recently reported that co-administration of morphine with dipyrone (metamizol) produces analgesic potentiation both in naïve and in morphine-tolerant rats. The purpose of this work was to determine the role of opioids on the acute potentiation observed between morphine and dipyrone i.v. in the rat tail flick test. To do this, two experiments were done. In the first one, naloxone was administered 10 min before morphine (3.1 mg/kg), dipyrone (600 mg/kg) or their combination at the same doses. Control animals received saline instead of naloxone. In the second experiment, naloxone (or saline) was given 2 min after reaching the maximal peak effect with each individual analgesic treatment. When naloxone was i.v. administered prior to analgesics, it completely blocked morphine effects, partially prevented morphine/dipyrone antinociception and delayed dipyrone-induced nociception. At 3.1 mg/kg, naloxone produced an increased nociception. When naloxone was given after analgesics, it dose-dependently blocked the effects of morphine alone and in combination with dipyrone but with different potency in each case. As to dipyrone, naloxone delayed the time to antinociceptive peak effect. Taken together, these results support the notion that endogenous opioids are involved in the analgesic potentiation observed with the combination of morphine plus dipyrone.

Analgesics, Opioid↗

Differences in prescription opioid analgesic availability: comparing minority and white pharmacies across Michigan.

UNLABELLED: Little is known about physical barriers to adequate pain treatment for minorities. This investigation explored sociodemographic determinants of pain medication availability in Michigan pharmacies. A cross-sectional survey-based study with census data and data provided by Michigan community retail pharmacists was designed. Sufficient opioid analgesic supplies was defined as stocking at least one long-acting, short-acting, and combination opioid analgesic. Pharmacies located in minority ( or=70% white residents) zip code areas were randomly selected by using a 2-stage sampling selection process (response rate, 80%). For the 190 pharmacies surveyed, most were located in white areas (51.6%) and had sufficient supplies (84.1%). After accounting for zip code median age and stratifying by income, pharmacies in white areas (odds ratio, 13.36 high income vs 54.42 low income) and noncorporate pharmacies (odds ratio, 24.92 high income vs 3.61 low income) were more likely to have sufficient opioid analgesic supplies (P < .005). Racial differences in the odds of having a sufficient supply were significantly higher in low income areas when compared with high income areas. Having a pharmacy located near a hospital did not change the availability for opioid analgesics. Persons living in predominantly minority areas experienced significant barriers to accessing pain medication, with greater disparities in low income areas regardless of ethnic composition. Differences were also found on the basis of pharmacy type, suggesting variability in pharmacist's decision making. PERSPECTIVE: Michigan pharmacies in minority zip codes were 52 times less likely to carry sufficient opioid analgesics than pharmacies in white zip codes regardless of income. Lower income areas and corporate pharmacies were less likely to carry sufficient opioid analgesics. This study illustrates barriers to pain care and has public health implications.

Adult↗

Differences in the prevalence and severity of side effects based on type of analgesic prescription in patients with chronic cancer pain.

An understanding of the relationship between the type of analgesic prescription and the prevalence and severity of side effects is crucial in making appropriate treatment decisions. The purposes of this study were to determine if there were differences in the prevalence of side effects among four different types of analgesic prescriptions (i.e., no opioid, only an as needed (PRN) opioid, only an around-the-clock (ATC) opioid, or an ATC+PRN opioid); to determine if there were differences in the severity of side effects among the four prescription groups; and to determine the relationships between the total dose of opioid analgesic medication prescribed and taken and the severity of side effects. As part of a larger study, 174 cancer patients with bone metastasis reported their analgesic use and the prevalence and severity of 11 side effects. Significant differences (P<0.05) were found in prevalence rates for seven of the side effects among the four prescription groups. The highest prevalence rates were found in the only ATC and ATC+PRN groups. Significant differences were found in the severity scores for five of the side effects, with the highest severity scores reported by patients in the only ATC and ATC+PRN groups. Significant positive correlations were found between the severity of six of the side effects and the total dose of opioid prescribed and taken. Risk factors for analgesic-induced side effects are ATC and ATC+PRN prescription types and higher doses of opioid analgesics.

Adult↗

Combination analgesics.

Six rationales for using combination analgesics are identified, but most combinations are formulated with two rationales in mind: enhancement of analgesia and reduction of adverse effects by combining two analgesics with different mechanisms of action. Acetaminophen and aspirin are the mainstays of oral analgesic combinations. There is substantial evidence that combining an optimal dose of acetaminophen or aspirin with an oral opioid such as codeine, hydrocodone, or oxycodone produces an additive analgesic effect greater than that obtained by doubling the dose of either constituent administered alone. There is also some evidence that the adverse effects produced by such combinations are less than would be produced by an equi-analgesic dose of a single constituent. The physician need not be confined to existing fixed-ratio combinations; he or she may extemporize to the patient's advantage by co-administering acetaminophen, aspirin, or other nonsteroidal anti-inflammatory drugs with available oral opioids and, in select situations, co-administering oral or injectable analgesics with psychoactive drugs.

Acetaminophen↗

Opiate receptors in the periaqueductal gray mediate analgesic effect of nitrous oxide in rats.

The site of action and the pathways which are activated by nitrous oxide (N2O) to produce an analgesic effect are not well defined. Experiments were designed to determine whether N2O produces analgesia by activating opiate receptors or alpha2-adrenoceptors in periaqueductal gray. The analgesic effect of N2O was determined using the tail flick response to noxious radiant heat in lightly anesthetized rats. Different antagonists were bilaterally microinjected into ventrolateral periaqueductal gray to determine whether the analgesic effect produced by N2O was reversed. The increase in the tail flick latencies produced by N2O was reversed by bilateral microinjection into the ventrolateral part of periaqueductal gray with the opiate receptor antagonist naloxone 2.5 microg/0.5 microl, but not with the alpha2-adrenoceptors antagonist yohimbine 1.5 microg/0.5 microl. These results indicate that the N2O analgesic effect is mediated by activation of opiate receptors, but not alpha2-adrenoceptors, in the periaqueductal gray. Combined with the previous experiments that the N2O analgesic effect is reversed by intrathecal injection of an alpha2-adrenoceptor antagonist but not by an opiate receptor antagonist, it seems likely that N2O causes activation of the opiate receptors in the periaqueductal gray, which in turn activate the noradrenergic descending pathways to the spinal cord to produce the analgesic effect.

Adrenergic alpha-Antagonists↗

Analgesic efficacy of the cyclooxygenase-2-specific inhibitor rofecoxib in post-dental surgery pain: a randomized, controlled trial.

Previous data have suggested that rofecoxib, a cyclooxygenase (COX)-2-specific inhibitor, had analgesic effects similar to those of the nonsteroidal anti-inflammatory drugs when tested in the post-dental surgery pain model. The objective of this parallel-group, double-masked, randomized, placebo- and active comparator-controlled clinical trial was to assess more fully the analgesic efficacy of rofecoxib in the treatment of postoperative dental pain. After dental surgery, 151 patients (50.3% women; mean age, 18.3 years; 93.4% white) experiencing moderate-to-severe pain were to receive a single dose of placebo, rofecoxib 50 mg, or ibuprofen 400 mg. Analgesic efficacy was assessed for up to 24 hours postdose using self-administered questionnaires. Tolerability was assessed using spontaneous reports of adverse experiences, physical findings, and laboratory measurements. The results of this study demonstrated that rofecoxib 50 mg was more effective than placebo on all measures of analgesic efficacy. Rofecoxib 50 mg exhibited overall analgesic effects, onset of analgesia, and peak analgesic effects that were not significantly different from those of ibuprofen 400 mg, with a significantly longer duration of action (P < 0.05). We concluded that rofecoxib was efficacious in the treatment of postoperative dental pain and that COX-2-derived prostanoids play a role in treatment of the pain associated with dental surgery.

Adolescent↗

General anesthesia and postoperative pain management in analgesic intolerant patients with/without asthma: is it safe?

BACKGROUND: Analgesic intolerance (AI) appears in approximately 1 % of the general population. The triad of bronchial asthma, nasal polyposis, and analgesic intolerance is called analgesic-induced asthma (AIA). These patients are frequently referred to adult allergy clinics for preoperative evaluation for possible analgesic cross reactivity and intolerance to anesthetic agents. OBJECTIVE: To determine allergic problems related to anesthesia and postoperative pain management in AI patients with and without asthma. METHODS: The medical records of 45 patients who had been diagnosed with AI between January 1991 and December 2002 in the adult allergy unit and who underwent surgery in the same hospital in the last 4 years were retrospectively analyzed. RESULTS: The mean age of the patients was 44.4 13.4 years and 30 (66.6 %) were female. Thirty-six (80 %) had AIA, 34 (75.6 %) had persistent allergic rhinitis and 21 (46.7 %) had nasal polyps. Fifty-one surgical procedures were performed in 45 patients, in whom ear, nose and throat surgery was the main procedure (64.7 %). Anesthesia was induced with propofol, fentanyl, and vecuronium and was maintained by sevoflurane or isoflurane. Fentanyl was used for early postoperative pain relief. No complications appeared in relation to anesthesia or early pain management except in a 44-year-old AIA woman who had a reaction in the postoperative period after receiving an inappropriate analgesic. CONCLUSIONS: None of the patients had anesthesia-related allergic problems. Atropine and diazepam in the premedication, propofol and fentanyl during induction, muscle relaxation facilitation by vecuronium, and sevoflurane or isoflurane for maintenance seem to be a safe general anesthetic choice for analgesic intolerant patients with and without asthma.

Adult↗

Pindolol, a beta-adrenoceptor blocker/5-hydroxytryptamine(1A/1B) antagonist, enhances the analgesic effect of tramadol.

The ability of pindolol, a beta-adrenoceptor blocker/5-hydroxytryptamine(1A/1B) antagonist, to enhance the clinical antidepressant response to selective serotonin re-uptake inhibitors is generally attributed to a blocking of the feedback that inhibits the serotoninergic neuronal activity mediated by somatodendritic 5-hydroxytryptamine (5-HT)(1A) autoreceptors. The current study examined the ability of pindolol to enhance the analgesic effect of tramadol, an atypical centrally-acting analgesic agent with relatively weak opioid receptor affinity and which, like some antidepressants, is able to inhibit the re-uptake of 5-HT in the raphe nuclei. Racemic pindolol (2 mg/kg, s.c.), rendered analgesic a non-effective acute dose of tramadol (10-40 mg/kg, i.p.) in two nociceptive tests: a hot plate test in mice and a plantar test in rats. Moreover, (+/-)8-OH-DPAT (0.125-1 mg/kg, s.c.), a selective 5-HT(1A) agonist, reduces the analgesic effect of tramadol in the same tests. These results suggest an implication of the somatodendritic 5-HT(1A) receptors in the analgesic effect of tramadol and open a new adjuvant analgesic strategy for the use of this compound.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Loss of analgesic effect of morphine due to coadministration of rifampin.

Methadone withdrawal symptoms have been reported in drug addicts treated with the tuberculostatic rifampin. Whereas this interaction can be explained by induction of phase I drug metabolism (CYP3A4), knowledge about induction of phase II metabolism (e.g., UDP-glucuronosyltransferases = UGTs) and its influence on drug effects in man, however, is very limited. The potent analgesic morphine is metabolized by more than one UGT to the active metabolite morphine-6-glucuronide and to morphine-3-glucuronide, which is devoid of analgesic activity. Thus, differential induction of UGTs involved in metabolism of morphine might lead to decreased or increased analgesic effects, depending on which UGT is preferentially induced. We therefore investigated the influence of the potent enzyme inducer rifampin on analgesic effects and pharmacokinetics of morphine, which is primarily eliminated by phase II metabolism. Ten healthy male volunteers participated in this double-blind, placebo-controlled study with double crossover design. Morphine (10 mg p.o.) and placebo were administered on two separate occasions before and near the end of 13 days of treatment with rifampin (600 mg/day). Blood samples were collected for 31 h. Morphine effects on pain sensation were determined using the cold pressor test. When morphine was given alone, the opioid elicited a significant increase in pain threshold and pain tolerance in comparison to placebo (P < or = 0.05). However, following administration of rifampin no analgesic effect of morphine was observed. In agreement, the area under the serum concentration-time curve (AUC) of morphine and the maximum serum concentration of morphine were considerably reduced during coadministration of rifampin (-27.7 +/- 19.3% and -40.7 +/- 27.1%; P < or = 0.01). Moreover, during treatment with rifampin a proportional reduction of AUCs of morphine-3-glucuronide (P < or = 0.01), morphine-6-glucuronide (P < or = 0.05) and morphine was observed. Since urinary recoveries of both morphine-3-glucuronide and morphine-6-glucuronide were also reduced during administration of rifampin, there is no evidence for a contribution of UGT induction to the observed interaction. In summary, a major drug interaction was observed between morphine and rifampin, which could not be attributed to induction of UGTs, but resulted in a complete loss of analgesic effects of the opioid.

Adult↗

Impact of experimentally-induced expectancy on the analgesic efficacy of tramadol in chronic pain patients: a 2 x 2 factorial, randomized, placebo-controlled, double-blind trial.

Variations in treatment effects between drug trials are usually attributed to different patient characteristics, variations in outcome assessment, and random error. We have previously hypothesized that part of the variation in treatment effects between drug trials might be caused by differences in nonspecific factors. In a randomized clinical trial, we aimed to investigate whether experimentally induced expectancy can modify the analgesic effect of tramadol relative to placebo in chronic pain patients. In a 2 x 2 factorial, randomized, placebo-controlled, double-blind trial, chronic pain patients attending a chronic pain outpatient clinic were randomized to receive a single oral dose of 50 mg tramadol or placebo, and they were further randomized to receive positive or neutral information, verbally expressed by the physician, regarding the expected analgesic effect of the drug. Pain intensity was measured using a 10 centimeter visual analogue scale at baseline, and 0.5, 1, 2, 4, 6, and 8 hours after baseline. The one-hour pain intensity difference, calculated as the sum of pain intensity differences between baseline and 0.5 and 1 hour, was taken as main outcome measure. The one-hour sum of pain intensity differences of 28 patients treated after positive expectation and randomized to tramadol was 1.4 cm, while in 27 patients randomized to placebo, it was 0.8 cm. This corresponds with an analgesic effect of tramadol relative to placebo of 0.6 cm (95% confidence interval [CI], -0.5 cm to 1.8 cm). The 28 patients in the neutral expectancy group who were randomized to tramadol reported a 1.4 cm decrease on the sum of pain intensity differences, while 28 patients in the placebo group reported a 0.9 cm decrease. This corresponds with an analgesic effect of tramadol relative to placebo of 0.5 cm (95% CI, -0.9 cm to 1.8 cm). The 0.1 cm difference (0.6 cm - 0.5 cm) in analgesic effect between positive and neutral expectancy group was not statistically significant (95% CI, -0.7 cm to 1.0 cm). This trial did not discern a significant difference in the analgesic effect of tramadol between a positive and neutral expectancy group. This means that the phenomenon either does not exist, or we had an inappropriate model to demonstrate it. Regardless, this study demonstrates the type of quality trial that should be done to find out which non-specific factors, such as information regarding the expected effect, can modify treatment effects.

Adult↗

Comparison of the analgesic and intestinal effects of fentanyl and morphine in rats.

Clinical studies report a low incidence of intestinal side effects with transdermally administered fentanyl (TTS-fentanyl) in comparison with oral morphine. To support these clinical data, analgesic and intestinal effects of both opioids were compared in rats. After subcutaneous injection, analgesia in the tail withdrawal reaction test was obtained at a peak effect dose of 0.032 mg/kg with fentanyl and 8.0 mg/kg with morphine. This analgesic dose exceeded the ED50 for inhibition of castor oil-induced diarrhea only slightly (1.1 x) in the case of fentanyl (0.028 mg/kg) but markedly (36 x) in the case of morphine (0.22 mg/kg). To reverse completely the antidiarrheal effect of equivalent analgesic doses of the opioids (their ED50S for analgesia lasting 2 hours), much more naloxone was required in the case of morphine (5.4 mg/kg) than in the case of fentanyl (0.19 mg/kg). After oral administration, the difference between both opioids was less pronounced. Analgesia was obtained at 0.85 mg/kg with fentanyl and 32 mg/kg with morphine. This analgesic dose only slightly (1.7 x) exceeded the antidiarrheal dose in the case of fentanyl (0.49 mg/kg) but significantly (6.2 x) in the case of morphine (5.2 mg/ kg). To reverse completely the antidiarrheal effect of equivalent analgesic oral doses of the opioids (their ED50S for analgesia lasting 2 hours), more naloxone was required in the case of morphine (11 mg/kg) than in the case of fentanyl (2.0 mg/kg). Rapid penetration of fentanyl into the brain is thought to be responsible for small dissociation between the analgesic and intestinal effect of this lipophilic opioid. The present data provide preclinical evidence to support the relatively low incidence of intestinal side effects observed clinically with the use of TTS-fentanyl in comparison with orally administered morphine.

Analgesics, Opioid↗

Transcutaneous electrical nerve stimulation (TENS) can reduce postoperative analgesic consumption. A meta-analysis with assessment of optimal treatment parameters for postoperative pain.

AIM: We investigated the literature of randomised placebo-controlled trials to find out if transcutaneous electrical nerve stimulation (TENS) or acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) can reduce analgesic consumption after surgery. RESULTS: Subgroup analysis for adequate treatment (pulse frequency: 1-8Hz [ALTENS] or 25-150Hz [TENS], current intensity: "strong, definite, subnoxious, maximal tolerable" or above 15mA, and electrode placement in the incision area) were performed. Twenty-one randomised, placebo-controlled trials with a total of 1350 patients were identified. For all trials, the mean reduction in analgesic consumption after TENS/ALTENS was 26.5% (range -6 to +51%) better than placebo. Eleven of the trials compromising 964 patients, had reports which stated that a strong, subnoxious electrical stimulation with adequate frequency was administered. They reported a mean weighted reduction in analgesic consumption of 35.5% (range 14-51%) better than placebo. In nine trials without explicit confirmation of sufficient current intensity and adequate frequency, the mean weighted analgesic consumption was 4.1% (range -10 to +29%) in favour of active treatment. The difference in analgesic consumption was significantly (p=0.0002) in favour of adequate stimulation. The median frequencies used in trials with optimal treatment was 85Hz for TENS and 2Hz in the only trial that investigated ALTENS. CONCLUSION: TENS, administered with a strong, subnoxious intensity at an adequate frequency in the wound area, can significantly reduce analgesic consumption for postoperative pain.

Analgesics↗