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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 -
International Journal of Molecular... Oct 2020Palmitoylethanolamide (PEA, -hexadecanoylethanolamide) is an endogenous compound belonging to the family of -acylethanolamines. PEA has anti-inflammatory and analgesic... (Review)
Review
Palmitoylethanolamide (PEA, -hexadecanoylethanolamide) is an endogenous compound belonging to the family of -acylethanolamines. PEA has anti-inflammatory and analgesic properties and is very well tolerated in humans. In the present article, the basal pharmacology of PEA is reviewed. In terms of its pharmacokinetic properties, most work has been undertaken upon designing formulations for its absorption and upon characterising the enzymes involved in its metabolism, but little is known about its bioavailability, tissue distribution, and excretion pathways. PEA exerts most of its biological effects in the body secondary to the activation of peroxisome proliferator-activated receptor-α (PPAR-α), but PPAR-α-independent pathways involving other receptors (Transient Receptor Potential Vanilloid 1 (TRPV1), GPR55) have also been identified. Given the potential clinical utility of PEA, not least for the treatment of pain where there is a clear need for new well-tolerated drugs, we conclude that the gaps in our knowledge, in particular those relating to the pharmacokinetic properties of the compound, need to be filled.
Topics: Amides; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Biological Availability; Ethanolamines; Gene Expression Regulation; Humans; PPAR alpha; Palmitic Acids; Receptors, Cannabinoid; Tissue Distribution
PubMed: 33114698
DOI: 10.3390/ijms21217942 -
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 -
Anaesthesia Jul 2021Tonsillectomy is one of the most frequently performed surgical procedures; however, pain management remains challenging. Procedure-specific efficacy as well as specific...
Tonsillectomy is one of the most frequently performed surgical procedures; however, pain management remains challenging. Procedure-specific efficacy as well as specific risks of treatment options should guide selection of pain management protocols based on evidence and should optimise analgesia without harm. The aims of this systematic review were to evaluate the available literature and develop recommendations for optimal pain management after tonsillectomy. A systematic review utilising preferred reporting items for systematic reviews and meta-analysis guidelines with procedure-specific postoperative pain management (PROSPECT) methodology was undertaken. Randomised controlled trials published in the English language up to November 2019 assessing postoperative pain using analgesic, anaesthetic or surgical interventions were identified. Out of the 719 potentially eligible studies identified, 226 randomised controlled trials met the inclusion criteria, excluding the studies examining surgical techniques. Pre-operative and intra-operative interventions that improved postoperative pain were paracetamol; non-steroidal anti-inflammatory drugs; intravenous dexamethasone; ketamine (only assessed in children); gabapentinoids; dexmedetomidine; honey; and acupuncture. Inconsistent evidence was found for local anaesthetic infiltration; antibiotics; and magnesium sulphate. Limited evidence was found for clonidine. The analgesic regimen for tonsillectomy should include paracetamol; non-steroidal anti-inflammatory drugs; and intravenous dexamethasone, with opioids as rescue analgesics. Analgesic adjuncts such as intra-operative and postoperative acupuncture as well as postoperative honey are also recommended. Ketamine (only for children); dexmedetomidine; or gabapentinoids may be considered when some of the first-line analgesics are contra-indicated. Further randomised controlled trials are required to define risk and combination of drugs most effective for postoperative pain relief after tonsillectomy.
Topics: Acupuncture; Analgesia; Analgesics; Anesthetics, Local; Anti-Inflammatory Agents, Non-Steroidal; Child; Honey; Humans; Pain Management; Pain, Postoperative; Practice Guidelines as Topic; Tonsillectomy
PubMed: 33201518
DOI: 10.1111/anae.15299 -
Neurology India 2021Medication overuse headache (MOH) is one of the highly disabling headache disorder and affects about 1% of the population of the world. It is associated with the... (Review)
Review
BACKGROUND
Medication overuse headache (MOH) is one of the highly disabling headache disorder and affects about 1% of the population of the world. It is associated with the development of headache for 15 days or more, with consumption of acute symptomatic medications for 10-15 days (depending on the class of drug, like, simple analgesics, triptans, and opioids) in a month, used for relief of headache for three or more months, in a known patient of primary headache disorder.
OBJECTIVE
The aim of this study was to review the topic of MOH and present the details of this disorder with an emphasis on recent updates in the field of pathophysiology and treatment.
MATERIAL AND METHODS
Literature search was performed in the PubMed/MEDLINE and Cochrane database with appropriate keywords and relevant full-text articles were reviewed for writing this article.
RESULTS
Over the years, the concept of MOH has evolved, although the exact pathophysiology is still being explored. In a susceptible individual interplay of genetics, change in pain pathways, changes in areas of the brain associated with the perception of pain, and changes in the neurotransmitters have been implicated. It has to be differentiated from other secondary chronic daily headache disorders, by a careful history, targeted examination, details of intake of medications. Treatment predominantly involves patient education, removal of the offending agent, and initiation of prophylactic medications for primary headache disorder in the outpatient or inpatient services.
CONCLUSIONS
MOH is a secondary headache disorder, which should be considered in any chronic headache patient. There are various pathophysiological mechanisms attributed to its development. Management includes educating the patients about the disorder, detoxification, and prophylactic therapy.
Topics: Analgesics; Brain; Headache; Headache Disorders; Headache Disorders, Secondary; Humans
PubMed: 34003151
DOI: 10.4103/0028-3886.315981 -
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 -
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 -
Science Translational Medicine May 2022The transition from acute to chronic pain is critically important but not well understood. Here, we investigated the pathophysiological mechanisms underlying the...
The transition from acute to chronic pain is critically important but not well understood. Here, we investigated the pathophysiological mechanisms underlying the transition from acute to chronic low back pain (LBP) and performed transcriptome-wide analysis in peripheral immune cells of 98 participants with acute LBP, followed for 3 months. Transcriptomic changes were compared between patients whose LBP was resolved at 3 months with those whose LBP persisted. We found thousands of dynamic transcriptional changes over 3 months in LBP participants with resolved pain but none in those with persistent pain. Transient neutrophil-driven up-regulation of inflammatory responses was protective against the transition to chronic pain. In mouse pain assays, early treatment with a steroid or nonsteroidal anti-inflammatory drug (NSAID) also led to prolonged pain despite being analgesic in the short term; such a prolongation was not observed with other analgesics. Depletion of neutrophils delayed resolution of pain in mice, whereas peripheral injection of neutrophils themselves, or S100A8/A9 proteins normally released by neutrophils, prevented the development of long-lasting pain induced by an anti-inflammatory drug. Analysis of pain trajectories of human subjects reporting acute back pain in the UK Biobank identified elevated risk of pain persistence for subjects taking NSAIDs. Thus, despite analgesic efficacy at early time points, the management of acute inflammation may be counterproductive for long-term outcomes of LBP sufferers.
Topics: Acute Pain; Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Chronic Pain; Humans; Inflammation; Low Back Pain; Mice; Neutrophil Activation
PubMed: 35544595
DOI: 10.1126/scitranslmed.abj9954