Caffeine as an opioid analgesic adjuvant in fibromyalgia.
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ABSTRACT:
SUBMITTER: Scott JR
PROVIDER: S-EPMC5546775 | biostudies-other | 2017
REPOSITORIES: biostudies-other
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Project description:BACKGROUND:This is an updated version of the original Cochrane review published in Issue 3, 2012. Caffeine has been added to common analgesics such as paracetamol, ibuprofen, and aspirin, in the belief that it enhances analgesic efficacy. Evidence to support this belief is limited and often based on invalid comparisons. OBJECTIVES:To assess the relative efficacy of a single dose of an analgesic plus caffeine against the same dose of the analgesic alone, without restriction on the analgesic used or the pain condition studied. We also assessed serious adverse events. SEARCH METHODS:We searched CENTRAL, MEDLINE, and EMBASE from inception to 28 August 2014, the Oxford Pain Relief Database, and also carried out Internet searches and contacted pharmaceutical companies known to have carried out trials that have not been published. SELECTION CRITERIA:We included randomised, double-blind studies that compared a single dose of analgesic plus caffeine with the same dose of the analgesic alone in the treatment of acute pain. DATA COLLECTION AND ANALYSIS:Two review authors independently assessed the eligibility and quality of studies, and extracted data. Any disagreements or uncertainties were settled by discussion with a third review author. We sought any validated measure of analgesic efficacy, but particularly the number of participants experiencing at least 50% of the maximum possible pain relief over four to six hours, participants reporting a global evaluation of treatment of very good or excellent, or headache relief after two hours. We pooled comparable data to look for a statistically significant difference, and calculated numbers needed to treat to benefit (NNT) with caffeine. We also looked for any numerical superiority associated with the addition of caffeine, and information about any serious adverse events. MAIN RESULTS:We identified no new studies with available results for this update. The earlier review included 20 studies (7238 participants) in valid comparisons, but because we used different outcomes for some headache studies, the number of participants in the analyses of the effects of caffeine is now 4262 when previously it was 5243. The studies were generally of good methodological quality, using standard designs and mostly standard scales of pain measurement, although many of those treating postoperative pain were small.Most studies used paracetamol or ibuprofen, with 100 mg to 130 mg caffeine, and the most common pain conditions studied were postoperative dental pain, postpartum pain, and headache. There was a small but statistically significant benefit with caffeine used at doses of 100 mg or more, which was not dependent on the pain condition or type of analgesic. About 5% to 10% more participants achieve a good level of pain relief (at least 50% of the maximum over four to six hours) with the addition of caffeine, giving a NNT of about 14 (high quality evidence).Most comparisons individually demonstrated numerical superiority with caffeine, but not statistical superiority. One serious adverse event was reported with caffeine, but was considered unrelated to any study medication.We know of the existence of around 25 additional studies with almost 12,500 participants for which data for analysis were not obtainable. The additional analgesic effect of caffeine remained statistically significant but clinically less important even if all the known missing data had no effect; the bulk of the unobtainable data are reported to have similar results as this review. AUTHORS' CONCLUSIONS:The addition of caffeine (? 100 mg) to a standard dose of commonly used analgesics provides a small but important increase in the proportion of participants who experience a good level of pain relief.
| S-EPMC6485702 | biostudies-literature
Project description:BackgroundNon-opioid analgesics are prescribed in combination with opioids among patients with long bone fracture to reduce opioid prescribing needs, yet evidence is limited on whether they reduce the risk of serious opioid-related events (SOREs). We compared the risk of SOREs among hospitalized patients with long bone fracture discharged with filled opioid prescriptions, with and without non-opioid analgesics.DesignWe identified a retrospective cohort of analgesic-naïve adult patients with a long bone fracture hospitalization using the Merative MarketScan Commercial Database (2013-2020). The exposure was opioid and non-opioid analgesic (gabapentinoids, muscle relaxants, non-steroidal anti-inflammatory drugs, acetaminophen) prescriptions filled in the 3 days before through 42 days after discharge. The outcome was the development of new persistent opioid use or opioid use disorder during follow-up (day 43 through day 408 after discharge). We used Cox proportional hazards regression with inverse probability of treatment weighting with overlap trimming to compare outcomes among those that filled an opioid and a non-opioid analgesic to those that filled only an opioid analgesic. In secondary analyses, we used separate models to compare those that filled a prescription for each specific non-opioid analgesic type with opioids to those that filled only opioids.ResultsOf 29 489 patients, most filled an opioid prescription alone (58.4%) or an opioid and non-opioid (22.0%). In the weighted proportional hazards regression model accounting for relevant covariates and total MME, filling both a non-opioid analgesic and an opioid analgesic was associated with 1.63 times increased risk of SOREs compared with filling an opioid analgesic only (95% CI 1.41 to 1.89). Filling a gabapentin prescription in combination with an opioid was associated with an increased risk of SOREs compared with those that filled an opioid only (adjusted HR: 1.84 (95% CI1.48 to 2.27)).ConclusionsFilling a non-opioid analgesic in combination with an opioid was associated with an increased risk of SOREs after long bone fracture.Level of evidenceLevel III, prognostic/epidemiological.Study typeRetrospective cohort study.
| S-EPMC11253739 | biostudies-literature
Project description:A 2012 committee opinion from the American College of Obstetricians and Gynecologists highlights the considerable increase in opioid addiction in recent years, yet little is known about clinical correlates of prescribed opioids among pregnant women. This study examines clinical and demographic factors associated with the use of opioid analgesics in pregnancy. Data were derived from a prospective cohort study of pregnant women. Participants were administered the Composite International Diagnostic Interview to identify depressive and anxiety disorders and data on medication use were gathered at three assessment points and classified according to the Anatomical Therapeutic Chemical Code (ATC) classification system ATC group N02A. Participants included 2,748 English or Spanish speaking pregnant women. Six percent (n = 165) of women used opioid analgesics at any point in pregnancy. More pregnant women using opioids met diagnostic criteria for major depressive disorder (16 vs. 8 % for non users), generalized anxiety disorder (18 vs. 9 % for non users), post-traumatic stress disorder (11 vs. 4 % for non users) and panic disorder (6 vs. 4 % for non users). Women who reported opioid use were also significantly more likely than non users to report using illicit drugs and almost three times as likely to report smoking cigarettes in the second or third trimester of pregnancy (4 and 23 %, respectively) as compared to non-opioid users (0.5 and 8 %). The use of opioids in pregnancy was associated with higher levels of psychiatric comorbidity and use of other substances as compared to non-opioid users.
| S-EPMC4272915 | biostudies-literature
Project description:BACKGROUND:Levorphanol is a potent analgesic that has been used for decades. Most commonly used for acute and cancer pain, it also is effective against neuropathic pain. The recent appreciation of the importance of functional bias and the uncovering of multiple µ opioid receptor splice variants may help explain the variability of patient responses to different opioid drugs. METHODS:Here, we evaluate levorphanol in a variety of traditional in vitro receptor binding and functional assays. In vivo analgesia studies using the radiant heat tail flick assay explored the receptor selectivity of the responses through the use of knockout (KO) mice, selective antagonists, and viral rescue approaches. RESULTS:Receptor binding studies revealed high levorphanol affinity for all the ?, ?, and ? opioid receptors. In S-GTP?S binding assays, it was a full agonist at most µ receptor subtypes, with the exception of MOR-1O, but displayed little activity in ?-arrestin2 recruitment assays, indicating a preference for G-protein transduction mechanisms. A KO mouse and selective antagonists confirmed that levorphanol analgesia was mediated through classical µ receptors, but there was a contribution from 6 transmembrane targets, as illustrated by a lower response in an exon 11 KO mouse and its rescue with a virally transfected 6 transmembrane receptor splice variant. Compared to morphine, levorphanol had less respiratory depression at equianalgesic doses. CONCLUSIONS:While levorphanol shares many of the same properties as the classic opioid morphine, it displays subtle differences that may prove helpful in its clinical use. Its G-protein signaling bias is consistent with its diminished respiratory depression, while its incomplete cross tolerance with morphine suggests it may prove valuable clinically with opioid rotation.
| S-EPMC6181797 | biostudies-literature
Project description:Opioid misuse is a public health crisis in the United States. The origin of this crisis is associated with a sharp increase in opioid analgesic prescribing. We used the urban scaling framework to analyze opioid prescribing patterns in US commuting zones (CZs), i.e., groups of counties based on commuting patterns. The urban scaling framework postulates that a set of scaling relations can be used to predict health outcomes and behaviors in cities. We used data from the Drug Enforcement Administration's Automated Reports and Consolidated Ordering System (ARCOS) to calculate counts of oxycodone/hydrocodone pills distributed to 607 CZs in the continental US from 2006 to 2014. We estimated the scaling coefficient of opioid pill counts by regressing log(pills) on log(population) using a piecewise linear spline with a single knot at 82,363. Our results show that CZs with populations below the knot scaled superlinearly (β = 1.36), i.e., larger CZs had disproportionally larger pill counts compared to smaller CZs. On the other hand, CZs with populations above the knot scaled sublinearly (β = 0.92), i.e., larger CZs had disproportionally smaller pill counts compared to smaller CZs. This dual scaling pattern was consistent across US census regions. For CZs with population below the knot, the superlinear scaling of pills is consistent with the explanation that an increased number of successful matches between prescribers and users will lead to higher prescribing rates. The non-linear scaling behavior observed could be the result of a combination of factors, including stronger health care systems and prescribing regulation in largely populated commuting zones, as well as high availability of other opioids such as heroin in these commuting zones. Future research should explore potential mechanisms for the non-linearity of prescription opioid pills.
| S-EPMC8509933 | biostudies-literature
Project description:Previous studies indicated that addition of the antihistaminic chlorpheniramine to the usual combination of acetylsalicylic acid, acetaminophen, and caffeine further increases their synergism both in terms of anti-inflammatory and analgesic effect. The present non-interventional study tested the superiority of two Algopirin® tablets, containing a total of 250 mg acetylsalicylic acid (ASA), 150 mg acetaminophen (paracetamol, PAR), 30 mg caffeine (CAF) and 4 mg chlorpheniramine (CLF) vs. a combination containing 250 mg ASA, 250 mg PAR, and 65 mg CAF recognized as "safe and effective" by FDA in treating migraine. Patients evaluated their pain intensity on the Visual Analog Scale-VAS(PI) before and 30, 60, 120, 180, and 240 min after drug intake. Interpretation of the pain curves as "survival pain curves" was considered as a method for direct comparison of the pain curves. This interpretation permitted the application of the log rank test for comparison of pain hazards. The results of the applied parametric and non-parametric statistical tests indicated significant differences between the main endpoints: both Areas Under Pain Curves and time to decrease of the pain intensity to less than 50% of the initial value comparisons highlighted that Algopirin® was more efficient in spite of smaller doses of PAR and CAF. Comparison of "survival of pain" led to the same conclusion concerning the superiority of Algopririn. Consequently, the addition of CLF permitted decreasing of ASA, PAR, and CAF doses as well as their potential side effects, without a loss of analgesic effect.
| S-EPMC5660851 | biostudies-literature
Project description:In a previous communication, our efforts leading from 1 to the identification of spiro[cyclohexane-dihydropyrano[3,4-b]indole]-amine 2a as analgesic NOP and opioid receptor agonist were disclosed and their favorable in vitro and in vivo pharmacological properties revealed. We herein report our efforts to further optimize lead 2a, toward trans-6'-fluoro-4',9'-dihydro-N,N-dimethyl-4-phenyl-spiro[cyclohexane-1,1'(3'H)-pyrano[3,4-b]indol]-4-amine (cebranopadol, 3a), which is currently in clinical development for the treatment of severe chronic nociceptive and neuropathic pain.
| S-EPMC4137374 | biostudies-literature
Project description:The prescription of opioid analgesics by dental professionals is widespread in the United States. Policy makers, government agencies, and professional organizations consider this phenomenon a growing public health concern. This study examined trends in the prescription of opioid analgesics for adults by dental professionals and associated factors in the United States. Data from the Medical Expenditure Panel Survey (1996-2013) were analyzed. Descriptive statistics were calculated separately for each year. Logistic regression analyses were conducted to estimate the overall trend during the period with and without adjusting for dental procedures and personal characteristics. Survey weights were incorporated to handle the sampling design. The prescription of opioid analgesics following dental care increased over time. After adjusting for sociodemographic factors, source of payment, and type of dental procedure, the odds ratio (OR) of prescribing opioid analgesics following a dental visit per each decade difference was 1.28 (95% confidence interval [CI], 1.19-1.38). Surgical, root canal, and implant procedures had the highest rates of opioid prescriptions and the greatest increases in rates over the study period. After adjusting for personal characteristics and type of dental procedure, the OR of receiving a prescription for opioids comparing blacks, Asians, and Hispanics to whites was 1.29 (95% CI, 1.17-1.41), 0.57 (95% CI, 0.47-0.70), and 0.84 (95% CI, 0.75-0.95), respectively. Opioid analgesic prescriptions following dental visits increased over time after adjusting for personal characteristics and type of dental procedure. The odds of receiving a prescription for opioids were higher for certain racial/ethnic minority groups. Knowledge Transfer Statement: This study highlights dental professionals prescribing practices of opioid analgesics by following dental treatments in the United States. With this knowledge, appropriate guidelines, protocols, and policies can be developed and implemented to address any inappropriate prescribing practices of opioid analgesics. In addition, this information could lead to an improvement in the prescribing practices of dental professionals and to evidence-based therapeutic decision making.
| S-EPMC5576054 | biostudies-literature
Project description:Background and purposeThe midbrain periaqueductal grey (PAG) plays a central role in modulating pain through a descending pathway that projects indirectly to the spinal cord via the rostroventral medial medulla (RVM). While opioids are potent analgesics that target the PAG, their cellular actions on descending projection neurons are unclear.Experimental approachPatch clamp recordings in voltage- and current-clamp mode were made from acutely prepared PAG slices from animals that received retrograde tracer injections into the RVM.Key resultsThe μ-agonist DAMGO reduced GABAergic evoked inhibitory postsynaptic currents (IPSCs) in retro-labelled, RVM-projecting neurons to a greater extent than in unlabelled neurons. The κ-opioid agonist U69593 reduced evoked IPSCs to a similar extent in both neuronal groups, while the δ-opioid agonist deltorphin-II was without effect. DAMGO and U69593 both produced a reduction in the rate, but not amplitude of spontaneous miniature IPSCs and asynchronous evoked IPSCs in retro-labelled neurons. DAMGO and U69593 also suppressed glutamatergic EPSCs in retro-labelled and unlabelled neurons. The DAMGO inhibition of evoked EPSCs, however, was less than that for evoked IPSCs in retro-labelled, but not unlabelled neurons. In current clamp, DAMGO produced a depolarizing increase in evoked postsynaptic potentials in retro-labelled neurons, but directly inhibited unlabelled neurons.Conclusion and implicationsThese findings suggest that μ-opioids activate the descending analgesic pathway from the midbrain PAG by a combination of presynaptic disinhibition of RVM-projecting neurons and postsynaptic inhibition of presumptive interneurons.
| S-EPMC7174888 | biostudies-literature
Project description:Opioid analgesic tolerance, a root cause of opioid overdose and misuse, can develop through an associative learning. Despite intensive research, the locus and central pathway subserving the associative opioid analgesic tolerance (AOAT) remains unclear. Using a combination of chemo/optogenetic manipulation with calcium imaging and slice physiology, here we identify neuronal ensembles in a hierarchically organized pathway essential for AOAT. The association of morphine-induced analgesia with an environmental condition drives glutamatergic signaling from ventral hippocampus (vHPC) to dorsomedial prefrontal cortex (dmPFC) cholecystokininergic (CCKergic) neurons. Excitation of CCKergic neurons, which project and release CCK to basolateral amygdala (BLA) glutamatergic neurons, relays AOAT signal through inhibition of BLA μ-opioid receptor function, thereby leading to further loss of morphine analgesic efficacy. This work provides evidence for a circuit across different brain regions distinct for opioid analgesic tolerance. The components of this pathway are potential targets to treat opioid overdose and abuse.
| S-EPMC9908028 | biostudies-literature