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Medicina (Kaunas, Lithuania) Jan 2022: Transcutaneous electrical stimulation of low- and medium-frequency currents is commonly used in pain management. Interferential current (IFC) therapy, a medium... (Review)
Review
: Transcutaneous electrical stimulation of low- and medium-frequency currents is commonly used in pain management. Interferential current (IFC) therapy, a medium frequency alternating current therapy that reportedly reduces skin impedance, can reach deeper tissues. IFC therapy can provide several different treatment possibilities by adjusting its parameters (carrier frequency, amplitudemodulated frequency, sweep frequency, sweep mode or swing pattern, type of application (bipolar or quadripolar), time of application and intensity). The objective of this review article is to discuss the literature findings on the analgesic efficacy of IFC therapy. : According to the literature, IFC therapy shows significant analgesic effects in patients with neck pain, low back pain, knee osteoarthritis and post-operative knee pain. Most of the IFC parameters seem not to influence its analgesic effects. We encourage further studies to investigate the mechanism of action of IFC therapy.
Topics: Analgesics; Electric Stimulation Therapy; Humans; Low Back Pain; Pain Management; Transcutaneous Electric Nerve Stimulation
PubMed: 35056448
DOI: 10.3390/medicina58010141 -
Molecules (Basel, Switzerland) Mar 2018The comprehensive treatment of pain is multidimodal, with pharmacotherapy playing a key role. An effective therapy for pain depends on the intensity and type of pain,... (Review)
Review
The comprehensive treatment of pain is multidimodal, with pharmacotherapy playing a key role. An effective therapy for pain depends on the intensity and type of pain, the patients' age, comorbidities, and appropriate choice of analgesic, its dose and route of administration. This review is aimed at presenting current knowledge on analgesics administered by transdermal and topical routes for physicians, nurses, pharmacists, and other health care professionals dealing with patients suffering from pain. Analgesics administered transdermally or topically act through different mechanisms. Opioids administered transdermally are absorbed into vessels located in subcutaneous tissue and, subsequently, are conveyed in the blood to opioid receptors localized in the central and peripheral nervous system. Non-steroidal anti-inflammatory drugs (NSAIDs) applied topically render analgesia mainly through a high concentration in the structures of the joint and a provision of local anti-inflammatory effects. Topically administered drugs such as lidocaine and capsaicin in patches, capsaicin in cream, EMLA cream, and creams containing antidepressants (i.e., doxepin, amitriptyline) act mainly locally in tissues through receptors and/or ion channels. Transdermal and topical routes offer some advantages over systemic analgesic administration. Analgesics administered topically have a much better profile for adverse effects as they relieve local pain with minimal systemic effects. The transdermal route apart from the above-mentioned advantages and provision of long period of analgesia may be more convenient, especially for patients who are unable to take drugs orally. Topically and transdermally administered opioids are characterised by a lower risk of addiction compared to oral and parenteral routes.
Topics: Administration, Cutaneous; Administration, Topical; Analgesics; Analgesics, Opioid; Animals; Humans; Pain
PubMed: 29562618
DOI: 10.3390/molecules23030681 -
Progres En Urologie : Journal de... Jul 2022This randomized, crossover, double-blind, controlled trial evaluates the efficacy and safety of a preprogrammed transcutaneous electrical nerve stimulation (TENS) device... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
This randomized, crossover, double-blind, controlled trial evaluates the efficacy and safety of a preprogrammed transcutaneous electrical nerve stimulation (TENS) device versus placebo (SHAM) in women with primary dysmenorrhea (PD).
MATERIAL
Forty women suffering from significant dysmenorrhea requiring the use of analgesics and/or non-steroidal anti-inflammatory drugs self-apply to the abdominal or lumbar region depending on the location of the pain, alternately according to randomization, the TENS device then the SHAM (dummy device) or conversely SHAM then TENS. The primary endpoint compares the evolution of pain intensity before and after application of TENS and SHAM. The speed of action, the persistence of the analgesic effect and the therapeutic savings are also evaluated. Adverse events (AEs) are collected.
RESULTS
A statistically and clinically significant decrease in the pain of 53% (P<0.0001) is observed during the first 2 applications of TENS versus no analgesic effect (-5%, P=0.318) with SHAM. Over all 197 applications of TENS, the reduction of menstrual pain intensity by more than half is confirmed. The rapid relief, less than 20 minutes in 74% of cases, lasts on average more than 7 hours. A difference in analgesic consumption of -93% is observed in favor of TENS (P<0.01). Seven participants reported 10 non-serious AEs, 2 of which were possibly related to TENS.
CONCLUSION
The TENS device tested represents a well-tolerated, rapidly and lastingly effective non-pharmacological analgesic solution, capable of replacing or being combined with analgesics in the management of PD.
Topics: Analgesics; Double-Blind Method; Dysmenorrhea; Female; Humans; Pain Measurement; Transcutaneous Electric Nerve Stimulation; Treatment Outcome
PubMed: 35249825
DOI: 10.1016/j.purol.2022.01.005 -
British Journal of Anaesthesia Sep 2019Systemic administration of the local anaesthetic lidocaine is antinociceptive in both acute and chronic pain states, especially in acute postoperative and chronic... (Review)
Review
Systemic administration of the local anaesthetic lidocaine is antinociceptive in both acute and chronic pain states, especially in acute postoperative and chronic neuropathic pain. These effects cannot be explained by its voltage-gated sodium channel blocking properties alone, but the responsible mechanisms are still elusive. This narrative review focuses on available experimental evidence of the molecular mechanisms by which systemic lidocaine exerts its clinically documented analgesic effects. These include effects on the peripheral nervous system and CNS, where lidocaine acts via silencing ectopic discharges, suppression of inflammatory processes, and modulation of inhibitory and excitatory neurotransmission. We highlight promising objectives for future research to further unravel these antinociceptive mechanisms, which subsequently may facilitate the development of new analgesic strategies and therapies for acute and chronic pain.
Topics: Acute Pain; Analgesics; Anesthetics, Local; Anti-Inflammatory Agents, Non-Steroidal; Chronic Pain; Humans; Ion Channels; Lidocaine; Molecular Targeted Therapy; Synaptic Transmission
PubMed: 31303268
DOI: 10.1016/j.bja.2019.06.014 -
Annual Review of Pharmacology and... Jan 2023The study of chronic pain continues to generate ever-increasing numbers of publications, but safe and efficacious treatments for chronic pain remain elusive. Recognition... (Review)
Review
The study of chronic pain continues to generate ever-increasing numbers of publications, but safe and efficacious treatments for chronic pain remain elusive. Recognition of sex-specific mechanisms underlying chronic pain has resulted in a surge of studies that include both sexes. A predominant focus has been on identifying sex differences, yet many newly identified cellular mechanisms and alterations in gene expression are conserved between the sexes. Here we review sex differences and similarities in cellular and molecular signals that drive the generation and resolution of neuropathic pain. The mix of differences and similarities reflects degeneracy in peripheral and central signaling processes by which neurons, immune cells, and glia codependently drive pain hypersensitivity. Recent findings identifying critical signaling nodes foreshadow the development of rationally designed, broadly applicable analgesic strategies. However, the paucity of effective, safe pain treatments compels targeted therapies as well to increase therapeutic options that help reduce the global burden of suffering.
Topics: Female; Humans; Male; Chronic Pain; Sex Characteristics; Neuralgia; Analgesics; Neurons
PubMed: 36662582
DOI: 10.1146/annurev-pharmtox-051421-112259 -
Pain Research & Management 2014Neuropathic pain (NeP), redefined as pain caused by a lesion or a disease of the somatosensory system, is a disabling condition that affects approximately two million...
BACKGROUND
Neuropathic pain (NeP), redefined as pain caused by a lesion or a disease of the somatosensory system, is a disabling condition that affects approximately two million Canadians.
OBJECTIVE
To review the randomized controlled trials (RCTs) and systematic reviews related to the pharmacological management of NeP to develop a revised evidence-based consensus statement on its management.
METHODS
RCTs, systematic reviews and existing guidelines on the pharmacological management of NeP were evaluated at a consensus meeting in May 2012 and updated until September 2013. Medications were recommended in the consensus statement if their analgesic efficacy was supported by at least one methodologically sound RCT (class I or class II) showing significant benefit relative to placebo or another relevant control group. Recommendations for treatment were based on the degree of evidence of analgesic efficacy, safety and ease of use.
RESULTS
Analgesic agents recommended for first-line treatments are gabapentinoids (gabapentin and pregabalin), tricyclic antidepressants and serotonin noradrenaline reuptake inhibitors. Tramadol and controlled-release opioid analgesics are recommended as second-line treatments for moderate to severe pain. Cannabinoids are now recommended as third-line treatments. Recommended fourth-line treatments include methadone, anticonvulsants with lesser evidence of efficacy (eg, lamotrigine, lacosamide), tapentadol and botulinum toxin. There is support for some analgesic combinations in selected NeP conditions.
CONCLUSIONS
These guidelines provide an updated, stepwise approach to the pharmacological management of NeP. Treatment should be individualized for each patient based on efficacy, side-effect profile and drug accessibility, including cost. Additional studies are required to examine head-to-head comparisons among analgesics, combinations of analgesics, long-term outcomes and treatment of pediatric, geriatric and central NeP.
Topics: Analgesics; Canada; Chronic Pain; Humans; Neuralgia; Pain Management
PubMed: 25479151
DOI: 10.1155/2014/754693 -
The Cochrane Database of Systematic... Nov 2015Non-prescription (over-the-counter, or OTC) analgesics (painkillers) are used frequently. They are available in various brands, package sizes, formulations, and dose.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Non-prescription (over-the-counter, or OTC) analgesics (painkillers) are used frequently. They are available in various brands, package sizes, formulations, and dose. They can be used for a range of different types of pain, but this overview reports on how well they work for acute pain (pain of short duration, usually with rapid onset). Thirty-nine Cochrane reviews of randomised trials have examined the analgesic efficacy of individual drug interventions in acute postoperative pain.
OBJECTIVES
To examine published Cochrane reviews for information about the efficacy of pain medicines available without prescription using data from acute postoperative pain.
METHODS
We identified OTC analgesics available in the UK, Australia, Canada, and the USA by examining online pharmacy websites. We also included some analgesics (diclofenac potassium, dexketoprofen, dipyrone) of importance in parts of the world, but not currently available in these jurisdictions.We identified systematic reviews by searching the Cochrane Database of Systematic Reviews (CDSR) on The Cochrane Library through a simple search strategy. All reviews were overseen by a single review group, had a standard title, and had as their primary outcome numbers of participants with at least 50% pain relief over four to six hours compared with placebo. From individual reviews we extracted the number needed to treat for an additional beneficial outcome (NNT) for this outcome for each drug/dose combination, and also calculated the success rate to achieve at least 50% of maximum pain relief. We also examined the number of participants experiencing any adverse event, and whether the incidence was different from placebo.
MAIN RESULTS
We found information on 21 different OTC analgesic drugs, doses, and formulations, using information from 10 Cochrane reviews, supplemented by information from one non-Cochrane review with additional information on ibuprofen formulations (high quality evidence). The lowest (best) NNT values were for combinations of ibuprofen plus paracetamol, with NNT values below 2. Analgesics with values close to 2 included fast acting formulations of ibuprofen 200 mg and 400 mg, ibuprofen 200 mg plus caffeine 100 mg, and diclofenac potassium 50 mg. Combinations of ibuprofen plus paracetamol had success rates of almost 70%, with dipyrone 500 mg, fast acting ibuprofen formulations 200 mg and 400 mg, ibuprofen 200 mg plus caffeine 100 mg, and diclofenac potassium 50 mg having success rates above 50%. Paracetamol and aspirin at various doses had NNT values of 3 or above, and success rates of 11% to 43%. We found no information on many of the commonly available low dose codeine combinations.The proportion of participants experiencing an adverse event were generally not different from placebo, except for aspirin 1000 mg and (barely) ibuprofen 200 mg plus caffeine 100 mg. For ibuprofen plus paracetamol, adverse event rates were lower than with placebo.
AUTHORS' CONCLUSIONS
There is a body of reliable evidence about the efficacy of some of the most commonly available drugs and doses widely available without prescription. The postoperative pain model is predominantly pain after third molar extraction, which is used as the industry model for everyday pain. The proportion of people with acute pain who get good pain relief with any of them ranges from around 70% at best to less than 20% at worst; low doses of some drugs in fast acting formulations were among the best. Adverse events were generally no different from placebo. Consumers can make an informed choice based on this knowledge, together with availability and price. Headache and migraine were not included in this overview.
Topics: Acute Pain; Administration, Oral; Analgesics; Humans; Nonprescription Drugs; Numbers Needed To Treat; Randomized Controlled Trials as Topic; Review Literature as Topic
PubMed: 26544675
DOI: 10.1002/14651858.CD010794.pub2 -
Frontiers in Immunology 2023Clinical observations have found that prolonged use of analgesics increases the incidence of infection. However, the direct causal relationship between prescription...
INTRODUCTION
Clinical observations have found that prolonged use of analgesics increases the incidence of infection. However, the direct causal relationship between prescription analgesic use (PAU) and risk of infection (ROI) remains unclear.
METHODS
This study used Mendelian randomization (MR) design to estimate the causal effect of PAU on ROI, as well as their mediating factors. Genetic data on prescription analgesics use and immune cells were obtained from published GWAS. Additionally, data on ROI were extracted from the FinnGen database. Two-sample MR analysis and multivariate MR (MVMR) analysis were performed using inverse variance weighting (IVW) to ascertain the causal association between PAU and ROI. Finally, 731 immune cell phenotypes were analyzed for their mediating role between analgesics and infection.
RESULTS
Using two-sample MR, IVW modeling showed that genetically predicted opioid use was associated with increased risk of pulmonary infection (PI) (OR = 1.13, 95% CI: 1.05-1.21, 0.001) and upper respiratory infection (URI) (OR = 1.18, 95% CI: 1.08-1.30, 0.001); non-steroidal anti-inflammatory drugs (NSAIDs) were related to increased risk of skin and subcutaneous tissue infection (OR = 1.21, 95% CI: 1.05-1.39, = 0.007), and antimigraine preparations were linked to a reduced risk of virus hepatitis (OR = 0.79, 95% CI: 0.69-0.91, 0.001). In MVMR, the association of opioids with URI and PI remained after accounting for cancer conditions. Even with a stricter threshold ( 0.05/30), we found a significant causal association between opioids and respiratory infections (URI/PI). Finally, mediation analyses found that analgesics influence the ROI through different phenotypes of immune cells as mediators.
CONCLUSION
This MR study provides new genetic evidence for the causal relationship between PAU and ROI, and the mediating role of immune cells was demonstrated.
Topics: Humans; Mendelian Randomization Analysis; Analgesics; Analgesics, Opioid; Immunologic Factors; Prescriptions; Respiratory Tract Infections; Communicable Diseases
PubMed: 38193081
DOI: 10.3389/fimmu.2023.1319127 -
European Journal of Clinical... Dec 2021Effect size estimates of analgesic drugs can be misleading. Ibuprofen (400 mg, 600 mg, 800 mg), paracetamol (1000 mg, 500 mg), paracetamol 1000 mg/codeine 60 mg,... (Randomized Controlled Trial)
Randomized Controlled Trial
Analgesic effect of oral ibuprofen 400, 600, and 800 mg; paracetamol 500 and 1000 mg; and paracetamol 1000 mg plus 60 mg codeine in acute postoperative pain: a single-dose, randomized, placebo-controlled, and double-blind study.
PURPOSE
Effect size estimates of analgesic drugs can be misleading. Ibuprofen (400 mg, 600 mg, 800 mg), paracetamol (1000 mg, 500 mg), paracetamol 1000 mg/codeine 60 mg, and placebo were investigated to establish the multidimensional pharmacodynamic profiles of each drug on acute pain with calculated effect size estimates.
METHODS
A randomized, double-blind, single-dose, placebo-controlled, parallel-group, single-centre, outpatient, and single-dose study used 350 patients (mean age 25 year, range 18 to 30 years) of homogenous ethnicity after third molar surgery. Primary outcome was sum pain intensity over 6 h. Secondary outcomes were time to analgesic onset, duration of analgesia, time to rescue drug intake, number of patients taking rescue drug, sum pain intensity difference, maximum pain intensity difference, time to maximum pain intensity difference, number needed to treat values, adverse effects, overall drug assessment as patient-reported outcome measure (PROM), and the effect size estimates NNT and NNTp.
RESULTS
Ibuprofen doses above 400 mg do not significantly increase analgesic effect. Paracetamol has a very flat analgesic dose-response profile. Paracetamol 1000/codeine 60 mg gives similar analgesia as ibuprofen from 400 mg, but has a shorter time to analgesic onset. Active drugs show no significant difference in maximal analgesic effect. Other secondary outcomes support these findings. The frequencies of adverse effects were low, mild to moderate in all active groups. NNT and NTTp values did not coincide well with PROMs.
CONCLUSION
Ibuprofen doses above 400 mg for acute pain offer limited analgesic gain. Paracetamol 1000 mg/codeine 60 mg is comparable to ibuprofen doses from 400 mg. Calculated effect size estimates and PROM in our study seem not to relate well as clinical analgesic efficacy estimators.
TRIAL REGISTRATION
NCT00699114.
Topics: Acetaminophen; Adolescent; Adult; Analgesics; Codeine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Female; Humans; Ibuprofen; Male; Pain Measurement; Pain, Postoperative; Young Adult
PubMed: 34655316
DOI: 10.1007/s00228-021-03231-9 -
The Cochrane Database of Systematic... Sep 2015This is an updated version of the original Cochrane overview published in Issue 9, 2011. That overview considered both efficacy and adverse events, but adverse events... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of the original Cochrane overview published in Issue 9, 2011. That overview considered both efficacy and adverse events, but adverse events are now dealt with in a separate overview.Thirty-nine Cochrane reviews of randomised trials have examined the analgesic efficacy of individual drug interventions in acute postoperative pain. This overview brings together the results of those individual reviews and assesses the reliability of available data.
OBJECTIVES
To summarise the efficacy of pharmaceutical interventions for acute pain in adults with at least moderate pain following surgery who have been given a single dose of oral analgesic.
METHODS
We identified systematic reviews in the Cochrane Database of Systematic Reviews in The Cochrane Library through a simple search strategy. All reviews were overseen by a single review group, had a standard title, and had as their primary outcome the number of participants with at least 50% pain relief over four to six hours compared with placebo. For individual reviews, we extracted the number needed to treat for an additional beneficial outcome (NNT) for this outcome for each drug/dose combination, and also the percentage of participants achieving at least 50% maximum pain relief, the mean of mean or median time to remedication, and the percentage of participants remedicating by six, eight, 12, or 24 hours. Where there was adequate information for pairs of drug and dose (at least 200 participants, in at least two studies), we defined the addition of four comparisons of typical size (400 participants in total) with zero effect as making the result potentially subject to publication bias and therefore unreliable.
MAIN RESULTS
The overview included 39 separate Cochrane Reviews with 41 analyses of single dose oral analgesics tested in acute postoperative pain models, with results from about 50,000 participants in approximately 460 individual studies. The individual reviews included only high-quality trials of standardised design, methods, and efficacy outcome reporting. No statistical comparison was undertaken.Reliable results (high quality information) were obtained for 53 pairs of drug and dose in painful postsurgical conditions; these included various fixed dose combinations, and fast acting formulations of some analgesics. NNTs varied from about 1.5 to 20 for at least 50% maximum pain relief over four to six hours compared with placebo. The proportion of participants achieving this level of benefit varied from about 30% to over 70%, and the time to remedication varied from two hours (placebo) to over 20 hours. Good (low) NNTs were obtained with ibuprofen 200 mg plus paracetamol (acetaminophen) 500 mg (NNT compared with placebo 1.6; 95% confidence interval 1.5 to 1.8), ibuprofen fast acting 200 mg (2.1; 1.9 to 2.3); ibuprofen 200 mg plus caffeine 100 mg (2.1; 1.9 to 3.1), diclofenac potassium 50 mg (2.1; 1.9 to 2.5), and etoricoxib 120 mg (1.8; 1.7 to 2.0). For comparison, ibuprofen acid 400 mg had an NNT of 2.5 (2.4 to 2.6). Not all participants had good pain relief and, for many pairs of drug and dose, 50% or more did not achieve at least 50% maximum pain relief over four to six hours.Long duration of action (eight hours or greater) was found for etoricoxib 120 mg, diflunisal 500 mg, paracetamol 650 mg plus oxycodone 10 mg, naproxen 500/550 mg, celecoxib 400 mg, and ibuprofen 400 mg plus paracetamol 1000 mg.There was no evidence of analgesic effect for aceclofenac 150 mg, aspirin 500 mg, and oxycodone 5 mg (low quality evidence). No trial data were available in reviews of acemetacin, meloxicam, nabumetone, nefopam, sulindac, tenoxicam, and tiaprofenic acid. Inadequate amounts of data were available for nine drugs and doses, and data potentially susceptible to publication bias for 13 drugs and doses (very low quality evidence).
AUTHORS' CONCLUSIONS
There is a wealth of reliable evidence on the analgesic efficacy of single dose oral analgesics. Fast acting formulations and fixed dose combinations of analgesics can produce good and often long-lasting analgesia at relatively low doses. There is also important information on drugs for which there are no data, inadequate data, or where results are unreliable due to susceptibility to publication bias. This should inform choices by professionals and consumers.
Topics: Acute Pain; Administration, Oral; Adult; Analgesics; Humans; Pain, Postoperative
PubMed: 26414123
DOI: 10.1002/14651858.CD008659.pub3