SciCombinator

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Concept: Analgesics

32

Aspirin, nonsteroidal antiinflammatory drugs (NSAID), and acetaminophen are commonly used. Frequent use of analgesics has been associated with a higher risk of hearing loss. However, the association between duration of analgesic use and the risk of hearing loss is unclear. We investigated the relationship between duration of analgesic use and self-reported hearing loss among 55,850 women in the Nurses' Health Study. Cox proportional hazards regression was used to adjust for potential confounders. During 873,376 person-years of follow-up (1990-2012), longer durations of NSAID use (for >6 years of use compared with <1 year, multivariable-adjusted relative risk = 1.10, 95% confidence interval: 1.06, 1.15; P for trend < 0.001) and acetaminophen use (for >6 years of use compared with <1 year, multivariable-adjusted relative risk = 1.09, 95% confidence interval: 1.04, 1.14; P for trend < 0.001) were associated with higher risks of hearing loss. Duration of aspirin use was not associated with hearing loss (for >6 years of use compared with <1 year, multivariable-adjusted relative risk = 1.01, 95% confidence interval: 0.97, 1.05; P for trend = 0.35). In this cohort of women, longer durations of NSAID and acetaminophen use were associated with slightly higher risks of hearing loss, but duration of aspirin use was not. Considering the high prevalence of analgesic use, this may be an important modifiable contributor to hearing loss.

Concepts: Cyclooxygenase, Non-steroidal anti-inflammatory drug, Paracetamol, Ibuprofen, Diclofenac, Aspirin, Analgesic, Analgesics

27

We analyze the effects of a multimodal analgesic regimen on postoperative pain, function, adverse effects and satisfaction compared to patient-controlled analgesia (PCA). Thirty-six patients undergoing TKA were randomized to receive either (1) periarticular injection before wound closure (30cc 0.5% bupivacaine, 10mg MSO4, 15mg ketorolac) and multimodal analgesics (oxycodone, tramadol, ketorolac; narcotics as needed) or (2) hydromorphone PCA. Preoperative and postoperative data were collected for VAS pain scores, time to physical therapy milestones, hospital stay length, patient satisfaction, narcotic consumption and medication-related adverse effects. The multimodal group had lower VAS scores, fewer adverse effects, lower narcotic usage, higher satisfaction scores and earlier times to physical therapy milestones. Multimodal pain management protocol decreases narcotic usage, improves pain scores, increases satisfaction and enhances early recovery.

Concepts: Opioid, Pain, Morphine, Analgesic, Hydrocodone, Tramadol, Codeine, Analgesics

27

To perform a meta-analysis on the use of combined epidural-intrathecal analgesia during labor, including intrathecal fentanyl and/or morphine compared to usual epidural techniques.

Concepts: Systematic review, Morphine, Heroin, Meta-analysis, Epidural, Pethidine, Analgesics

27

The objective of this study was to compare the postoperative analgesic effects of dexketoprofen, tramadol, and buprenorphine in dogs undergoing ovariohysterectomy. Seventy-five adult female dogs were randomly assigned to receive an intravenous injection (IV) of 1mg/kg of dexketoprofen (D), 0.02mg/kg of buprenorphine (B) or 2mg/kg of tramadol (T). Pain assessment was performed during 48h after ovariohysterectomy using a dynamic interactive visual analogue scale (DIVAS) and Glasgow composite measure pain scale (CMPS-SF). Rescue analgesia was required in 43%, 21%, and 5% of dogs in the B, T, and D groups, respectively, with significant differences between B and D (p=0.010) groups. The DIVAS and CMPS-SF values of the B group were significantly higher than those of the T and D groups. The most common undesirable effect was dysphoria in dexketoprofen group. Tramadol and dexketoprofen provide superior postoperative analgesia compared with buprenorphine in dogs undergoing ovariohysterectomy.

Concepts: Opioid, Pain, Morphine, Analgesic, Buprenorphine, Methadone, Tramadol, Analgesics

26

Embryo transfer is a surgical technique that is widely used in reproductive biotechnology. Despite the ethical obligation to relieve animals' post-operative pain, analgesia is not routinely provided after embryo transfer surgery because it has been suggested that analgesics may be detrimental to embryo survival. Studies suggest, however, that the potential for adverse effects varies depending on the type of analgesic used and the timing of its administration. The authors carried out a study to determine whether pre-operatively administered tramadol, a synthetic analogue of codeine, influenced birth rate, litter survival or the post-operative body weights of surrogate dams. Compared with controls that were not given any analgesic, surrogate dams given tramadol had similar birth rates and similar body weights at all time points. The tramadol-treated surrogate dams showed a statistically significant increase in the number of offspring that survived to weaning. The authors conclude that pre-operatively administered tramadol does not harm the success rate of embryo transfer surgery and even may improve litter survival.

Concepts: Opioid, Paracetamol, Morphine, Analgesic, Hydrocodone, Tramadol, Codeine, Analgesics

12

Nonsteroidal anti-inflammatory drugs are used extensively for the management of acute and chronic pain, with ketorolac tromethamine being one of the most frequently used parenteral analgesics in the emergency department (ED). The drugs may commonly be used at doses above their analgesic ceiling, offering no incremental analgesic advantage while potentially adding risk of harm. We evaluate the analgesic efficacy of 3 doses of intravenous ketorolac in ED patients with acute pain.

Concepts: Non-steroidal anti-inflammatory drug, Paracetamol, Ibuprofen, Diclofenac, Analgesic, Celecoxib, Analgesics, Analgesic nephropathy

11

Grip strength deficit is a measure of pain-induced functional disability in rheumatic disease. We tested whether this parameter and tactile allodynia, the standard pain measure in preclinical studies, show parallels in their response to analgesics and basic mechanisms. Mice with periarticular injections of complete Freund’s adjuvant (CFA) in the ankles showed periarticular immune infiltration and synovial membrane alterations, together with pronounced grip strength deficits and tactile allodynia measured with von Frey hairs. However, inflammation-induced tactile allodynia lasted longer than grip strength alterations, and therefore did not drive the functional deficits. Oral administration of the opioid drugs oxycodone (1-8 mg/kg) and tramadol (10-80 mg/kg) induced a better recovery of grip strength than acetaminophen (40-320 mg/kg) or the nonsteroidal antiinflammatory drugs ibuprofen (10-80 mg/kg) or celecoxib (40-160 mg/kg); these results are consistent with their analgesic efficacy in humans. Functional impairment was generally a more sensitive indicator of drug-induced analgesia than tactile allodynia, as drug doses that attenuated grip strength deficits showed little or no effect on von Frey thresholds. Finally, ruthenium red (a nonselective TRP antagonist) or the in vivo ablation of TRPV1-expressing neurons with resiniferatoxin abolished tactile allodynia without altering grip strength deficits, indicating that the neurobiology of tactile allodynia and grip strength deficits differ. In conclusion, grip strength deficits are due to a distinct type of pain that reflects an important aspect of the human pain experience, and therefore merits further exploration in preclinical studies to improve the translation of new analgesics from bench to bedside.

Concepts: Opioid, Non-steroidal anti-inflammatory drug, Paracetamol, Ibuprofen, Morphine, Analgesic, Codeine, Analgesics

6

Bingpian is a time-honored herb in traditional Chinese medicine (TCM). It is an almost pure chemical with a chemical composition of (+)-borneol and has been historically used as a topical analgesic for millennia. However, the clinical efficacy of topical borneol lacks stringent evidence-based clinical studies and verifiable scientific mechanism. We examined the analgesic efficacy of topical borneol in a randomized, double-blind, placebo-controlled clinical study involving 122 patients with postoperative pain. Topical application of borneol led to significantly greater pain relief than placebo did. Using mouse models of pain, we identified the TRPM8 channel as a molecular target of borneol and showed that topical borneol-induced analgesia was almost exclusively mediated by TRPM8, and involved a downstream glutamatergic mechanism in the spinal cord. Investigation of the actions of topical borneol and menthol revealed mechanistic differences between borneol- and menthol-induced analgesia and indicated that borneol exhibits advantages over menthol as a topical analgesic. Our work demonstrates that borneol, which is currently approved by the US FDA to be used only as a flavoring substance or adjuvant in food, is an effective topical pain reliever in humans and reveals a key part of the molecular mechanism underlying its analgesic effect.

Concepts: Clinical trial, Effectiveness, Opioid, Pain, Placebo, Analgesic, Food and Drug Administration, Analgesics

3

Attrition rates of new analgesics during drug development are high; poor assay sensitivity with reliance on subjective outcome measures being a crucial factor.

Concepts: Opioid, Codeine, Analgesics

3

The classification of morphine as a step III analgesic, based on pharmacological data, creates a strong bias toward a belief in the efficacy of this drug. However, double-blind emergency-room trials showed similar levels of pain relief with intravenous acetaminophen as with intravenous morphine in patients with renal colic, low back pain or acute limb pain. In patients with chronic noncancer low back pain, morphine and other strong opioids in dosages of up to 100mg/day were only slightly more effective than their placebos, no more effective than acetaminophen, and somewhat less effective than nonsteroidal anti-inflammatory drugs (NSAIDs). In patients with osteoarthritis, strong opioids were not more effective than NSAIDs and, in some studies, than placebos. The only randomized controlled trial in patients with sciatica found no difference with the placebo. Chronic use of strong opioids can induce hyperalgesia in some patients. Hyperpathia with increased sensitivity to cold leading the patient to request higher dosages should suggest opioid-induced hyperalgesia. Pain specialists in the US have issued a petition asking that strong opioids be used in dosages no higher than 100mg/day of morphine-equivalent, in an effort to decrease the high rate of mortality due to the misuse and abuse of strong opioids (10,000 deaths/year in the US). Healthcare providers often overestimate the efficacy of step III analgesics, despite pain score decreases of only 0.8 to 1.2 points.

Concepts: Opioid, Non-steroidal anti-inflammatory drug, Paracetamol, Ibuprofen, Diclofenac, Analgesic, Celecoxib, Analgesics