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A triple-blind randomized clinical trial of different associations between dexamethasone and non-steroids anti-inflammatories for preemptive action in third molar extractions.
Momesso, GAC, Grossi-Oliveira, GA, Silva, WPP, Akira, R, Chiba, F, Polo, TOB, de Lima Neto, TJ, Rios, BR, Bassi, APF, Sumida, DH, et al
Scientific reports. 2021;(1):24445
Abstract
The aim of this study is to evaluate the preemptive analgesic effects of dexamethasone (DEX) alone or combined with non-steroidal anti-inflammatory drugs (NSAIDs) in third molar surgeries. The subjects were divided into five groups (n = 20 teeth/group); subjects received only 8 mg of dexamethasone 1 h before the surgical procedure (DEX group), or in combination with etodolac (DEX + ETO), ketorolac (DEX + KET), ibuprofen (DEX + IBU), loxoprofen (DEX + LOX). Paracetamol 750 mg was provided as the number of rescue analgesics (NRA). Salivary PGE2 expression was measured preoperatively and at 48 h. Edema and Maximum mouth opening (MMO) were measured postoperatively at 48 h and 7 days. A visual analog scale (VAS) was performed postoperatively at 6, 12, 24, 48, 72 h, and 7 days. Salivary expression of PGE2 showed a decrease only for the DEX group. Edema and MMO and NRA consumption showed no significant differences among the groups (P > 0.05). The VAS showed a significantly lower pain perception at 6 h after the surgery for the DEX + ETO and DEX + KET groups (P < 0.05). The combination of DEX and NSAIDS should be considered for preemptive acute postsurgical pain management in third molar surgery. In some drug associations such as dexamethasone 8 mg + NSAIDS (ETO and KET) in the pre-operative time, only a few rescue analgesics are necessary.
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A randomized comparative study of methylcobalamin, methylcobalamin plus pregabalin and methylcobalamin plus duloxetine in patients of painful diabetic neuropathy.
Sharma, C, Kaur, I, Singh, H, Grover, IS, Singh, J
Indian journal of pharmacology. 2021;(5):358-363
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CONTEXT Diabetic neuropathy affects 10.5%-32.2% of diabetic population posing clinical burden onto society. AIMS We aimed to study the efficacy, safety, and tolerability of methylcobalamin, methylcobalamin plus pregabalin, and methylcobalamin plus duloxetine in patients of painful diabetic neuropathy. SETTINGS AND DESIGN It is a prospective, randomized, open-label, interventional, and parallel-group study done in patients of painful diabetic neuropathy. MATERIALS AND METHODS A total of 100 patients were recruited and randomized to three study groups A, B, and C on methylcobalamin, methylcobalamin and pregabalin, and methylcobalamin and duloxetine, respectively. Patients were assessed at day 0 and 4, 8, and 12 weeks. The tuning fork test, monofilament test, Thermal Sensitivity testing, and Visual Analog Scale (VAS) were used to analyze vibration, pressure, thermal sensitivity, and pain. STATISTICAL ANALYSIS USED The results are expressed as mean ± standard deviation. Appropriate statistical methods were used to calculate P value (<0.05 - significant). RESULTS The increase in number of patients with vibration perception is 11.6%, 37.9%, and 41.4%; pressure sensation is 7.6%, 37.9%, and 37.9%; and thermal sensitivity is 15.4%, 31.1%, and 37.9% in Groups A, B, and C, respectively. The decrease in VAS scores is 0.58 ± 0.14, 3.82 ± 0.05, and 4.17 ± 0.48 in Groups A, B, and C correspondingly. The adverse effects reported in Groups A, B, and C are 0%, 6.9%, and 10.3%, respectively. CONCLUSIONS Group C is more efficacious when compared to Groups A and B while Group B is safer.
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Lack of Detection of the Analgesic Properties of PF-05089771, a Selective Nav 1.7 Inhibitor, Using a Battery of Pain Models in Healthy Subjects.
Siebenga, P, van Amerongen, G, Hay, JL, McDonnell, A, Gorman, D, Butt, R, Groeneveld, GJ
Clinical and translational science. 2020;(2):318-324
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Sodium channel blockers are used for the treatment of pain, but this is limited by the lack of selectivity for different sodium channel subtypes, which can result in central nervous system and cardiovascular side effects. As such, there is special interest in the Nav 1.7 subtype, which is expressed predominantly in nociceptive and sympathetic neurons. The aim was to demonstrate analgesic properties of a potent selective Nav 1.7 sodium channel blocker, PF-05089771, alone and concomitantly with pregabalin in healthy subjects using a battery of human evoked pain models. This was a double-blind, double-dummy, randomized, placebo-controlled, five-period cross-over study with PF-05089771 alone and PF-05089771 concomitantly with pregabalin as treatment arms with pregabalin, ibuprofen, and placebo as control arms (NCT02349607). A battery of human evoked pain models was used to investigate analgesic properties of PF-05089771. Twenty-five subjects were enrolled in the study of which 23 subjects completed all five periods. PF-05089771 alone did not differ from placebo on the primary pain end points. The same holds when comparing PF-05089771 concomitantly with pregabalin and pregabalin alone. Pregabalin showed significant effects relative to placebo on thermal pain on the normal skin and UVB skin (least squares means with 90% confidence interval: 0.63 (0.32-0.93) and 0.53 (0.11-0.96)), pressure stimulation (1.10 (1.04-1.18)), and cold pressor (1.22 (1.14-1.32)). Ibuprofen demonstrated significant effects on thermal pain UVB skin (1.26 (0.82-1.70)) and pressure stimulation assessment (1.08 (1.01-1.15)), consistent with historical results. This study did not demonstrate analgesic properties of PF-05089771 alone or concomitantly with pregabalin in a battery of pain models.
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Greater analgesic effects of sucrose in the neonate predict greater weight gain to age 18 months.
Lumeng, JC, Li, X, He, Y, Gearhardt, A, Sturza, J, Kaciroti, NA, Li, M, Asta, K, Lozoff, B
Appetite. 2020;:104508
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Intraoral sucrose has analgesic effects in the newborn period. The hedonic and analgesic effects of sucrose overlap and hedonic response to sweet food is associated with adiposity. The potential association between the analgesic effects of intraoral sucrose in the newborn period and subsequent weight gain has not been examined. Healthy, term newborns received 25% intraoral sucrose or water prior to metabolic screen heel stick. Negative affect, quiet alert behavior, and sleepiness were coded during heel stick. Weight and length were measured and z-score (WLZ) calculated at birth, 9, and 18 months. Mixed models tested associations of behavioral response to heel stick with WLZ trajectory among infants receiving sucrose (n = 154) versus water (n = 117). Among infants receiving sucrose prior to heel stick with birth WLZ ≥ the median, less negative affect and more sleepiness during heel stick were each associated with greater increases in WLZ. These associations were not present among infants receiving water only prior to heel stick. Greater analgesic effects of sucrose in the neonate were associated with greater future increases in WLZ, especially among infants with higher birth WLZ. Greater opioid-mediated newborn behavioral response to intraoral sucrose may be a marker for future obesity risk. CLINICAL TRIALS NUMBER NCT02728141.
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Long-term safety and efficacy of mirogabalin in Asian patients with diabetic peripheral neuropathic pain.
Baba, M, Matsui, N, Kuroha, M, Wasaki, Y, Ohwada, S
Journal of diabetes investigation. 2020;(3):693-698
Abstract
AIMS/INTRODUCTION Diabetic peripheral neuropathic pain (DPNP) affects the functionality, mood and sleep patterns of patients with diabetes. Mirogabalin, an α2 δ ligand with a slower dissociation for α2 δ-1 versus α2 δ-2 subunits, showed efficacy and safety in a randomized, double-blind, placebo-controlled, 14-week study in Asian patients with DPNP. This open-label extension study evaluated the long-term safety and efficacy of mirogabalin in Asian patients with DPNP. MATERIAL AND METHODS This 52-week open-label extension study was carried out in Japan, Korea and Taiwan in patients with DPNP. Patients received mirogabalin, initiated at 5 mg twice daily and increased to a flexible maintenance dosage of 10 or 15 mg twice daily. Adverse events were monitored throughout the study. Patients provided a self-assessment of pain using the Short-Form McGill Pain Questionnaire. RESULTS Of the 214 patients who entered the study, 172 (80.4%) completed the extension study. Of 172 patients who completed the study, 149 received the highest dosage of mirogabalin (15 mg twice daily). The most common treatment-emergent adverse events were nasopharyngitis, diabetic retinopathy, peripheral edema, somnolence, diarrhea, increased weight and dizziness. Most treatment-emergent adverse events were mild or moderate in severity. The incidence of treatment-emergent adverse events leading to treatment discontinuation was 13.1%. The visual analog scale and all other Short-Form McGill Pain Questionnaire subscales (sensory score, affective score, total score and present pain intensity) generally decreased over time from baseline until week 52. CONCLUSIONS This extension study showed the safety and efficacy of a long-term flexible dosing regimen of mirogabalin 10 or 15 mg twice daily in patients with DPNP.
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Effect of KATP channel blocker glibenclamide on levcromakalim-induced headache.
Al-Karagholi, MA, Ghanizada, H, Kokoti, L, Paulsen, JS, Hansen, JM, Ashina, M
Cephalalgia : an international journal of headache. 2020;(10):1045-1054
Abstract
INTRODUCTION Administration of ATP-sensitive potassium channel opener levcromakalim triggers headache in healthy volunteers and migraine attacks in migraine patients. Here, we investigated the effect of ATP-sensitive potassium channel blocker glibenclamide on levcromakalim-induced headache in healthy volunteers. METHODS In a randomized, double-blind, placebo-controlled, three-way cross-over study, 15 healthy volunteers aged 18-40 years were randomly allocated to receive glibenclamide and levcromakalim (day 1), glibenclamide and placebo (day 2), and placebo and placebo (day 3) on three different days separated by at least 1 week. The primary endpoints were the difference in incidence of headache and the difference in area under the curve for headache intensity scores (0-12 hours) between the days. RESULTS Fifteen healthy volunteers completed the 3 days of the study. More participants (12/15, 80%) developed headache on the glibenclamide-levcromakalim day compared to the glibenclamide-placebo day (5/15, 33%) (p = 0.01; mean difference 47%; 95% confidence interval 18-75%) and compared to the placebo-placebo day (1/15, 7%) (p = 0.001; mean difference 73%; 95% confidence interval 48-99%). We found no difference in headache incidence between glibenclamide-placebo day and placebo-placebo day (p = 0.12; mean difference 27%; 95% confidence interval 1.3-52%). The area under the curve for headache intensity was significantly larger on the glibenclamide-levcromakalim day compared to the glibenclamide-placebo day (p = 0.003); and compared to the placebo-placebo day (p = 0.001). We found no difference in the area under the curve between the glibenclamide-placebo day compared to the placebo-placebo day (p = 0.07). The median time to onset for headache after levcromakalim infusion with glibenclamide pretreatment was delayed (180 min) compared to levcromakalim without pretreatment (30 min) from a previously published study. CONCLUSION Glibenclamide administration did not cause headache, and glibenclamide pretreatment did not prevent levcromakalim-induced headache. However, glibenclamide delayed the onset of levcromakalim-induced headache. More selective blockers are needed to further elucidate the role of the ATP-sensitive potassium channel in headache initiation.Trial Registration: ClinicalTrials.gov NCT03886922.
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A comparative evaluation of transdermal diclofenac patch with oral diclofenac sodium as an analgesic drug following periodontal flap surgery: A randomized controlled clinical study.
Diwan, V, Srinivasa, TS, Ramreddy, KY, Agrawal, V, Nagdeve, S, Parvez, H
Indian journal of dental research : official publication of Indian Society for Dental Research. 2019;(1):57-60
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BACKGROUND Pain is an inevitable outcome of any periodontal surgery. Controlling postoperative pain is of utmost importance so as to increase patient compliance. The present study aims to compare the degree of postoperative analgesia with the use of oral diclofenac sodium and transdermal diclofenac patch following periodontal flap surgery in patients with chronic periodontitis. MATERIALS AND METHODS A total of 20 patients requiring full mouth flap surgery were selected for this study. Flap surgery was performed quadrant-wise and transdermal diclofenac patch was applied on the right arm following surgery of one of the quadrants and 100 mg oral diclofenac sodium twice daily was prescribed following surgery of the subsequent quadrant. The postoperative pain was recorded on visual analog scale and pain intensity scale 24 h after the surgery. RESULTS Both the statistical and clinical observation showed that diclofenac sodium administered transdermally has equal efficacy as compared to drug administered orally. CONCLUSION The study concludes that the diclofenac administered transdermally has equal potency in relieving postoperative pain as compared to orally administered diclofenac sodium following modified flap surgery. Transdermal patch has an added advantage of better patient compliance as it does not cause gastric disturbance.
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Comparison of the Post-Total Knee Arthroplasty Analgesic Effect of Intraoperative Periarticular Injection of Different Analgesics.
Liu, M, Zhang, D, Shi, B
Journal of the College of Physicians and Surgeons--Pakistan : JCPSP. 2019;(12):1169-1172
Abstract
OBJECTIVE To compare post-TKA (total knee arthroplasty) analgesic effect of periarticular injection of different analgesics during surgery. STUDY DESIGN Experimental study. PLACE AND DURATION OF STUDY Tianjin People's Hospital, from December 2016 to July 2018. METHODOLOGY Patients undergoing unilateral TKA were randomly divided into Group A and Group B, with 67 patients in each group. In Group A, compound analgesics of ropivacaine, ketorolac, adrenaline, morphine and normal saline were injected periarticularly during surgery. While in Group B, compound analgesics of bupivacaine, methylprednisolone, adrenalin, morphine and normal saline were injected periarticularly during surgery. Visual analogue scale (VAS), range of motion (ROM) of knee joint, and rehabilitation of knee joint of both groups were compared. RESULTS VAS scores of Group A at 6-hour, 24-hour, 48-hour and 72-hour after surgery was lower than those of Group B (p=0.046, p<0.001, p<0.001 and p<0.001, respectively). ROM of knee joint of Group A on the 3rd, 7th, 10th and 14th day after surgery was superior to that of Group B (all p<0.001). On the 14th day after surgery, excellent and good rate of rehabilitation of knee joint of Group A was higher than that of Group B (p=0.032). CONCLUSION Compared with periarticular injection of compound analgesics of bupivacaine, methylprednisolone, adrenaline, morphine and normal saline during surgery, periarticular injection of compound analgesics of ropivacaine, ketorolac, adrenaline, morphine and normal saline during surgery can alleviate post-TKA pain more effectively, improve early ROM of joint knee after surgery, increase rehabilitation effect of knee joint.
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Efficacy of pethidine, ketorolac, and lidocaine gel as analgesics for pain control in shockwave lithotripsy: A single-blinded randomized controlled trial.
Hashem, A, Ghobrial, FK, Elbaset, MA, Atwa, AM, Fadallah, M, Laymon, M, El-Assmy, A, Sheir, KZ, Abol-Enein, H
Investigative and clinical urology. 2019;(4):251-257
Abstract
PURPOSE To compare the safety and efficacy of xylocaine gel and ketorolac as opioid-sparing analgesia compared with pethidine for shock wave lithotripsy (SWL) pain. MATERIALS AND METHODS A single-blinded randomized controlled trial (RCT) was performed in 132 patients with renal and upper ureteral stones amenable to treatment with SWL. The first patient group received intravenous (IV) pethidine and placebo gel; the second group received IV ketorolac plus placebo gel; the third group received lidocaine gel locally plus normal saline IV. Stone disintegration was classified as none (no change from basal by kidney, ureter, bladder X-ray or ultrasound [US] imaging), partial (fragmented and >4-mm residual fragments), and complete (≤4-mm residual fragments). Stone disintegration was assessed by kidney-ureter-bladder X-ray and US imaging. Pain was evaluated by use of the Numeric Pain Rating Scale (NPRS). RESULTS The NPRS scores were highest in the xylocaine group at 10, 20, and 30 minutes (p=0.0001) with no significant difference between the ketorolac and pethidine groups, except at 10 minutes (p=0.03) and a near significant difference at 30 minutes (p=0.054) in favor of ketorolac. Results for stone disintegration (none, partial, and complete, respectively) were as follows: 25 (50.0%), 23 (46.0%), and 2 (4.0%) for pethidine; 19 (35.8%), 23 (43.4%), and 11 (20.8%) for ketorolac; and 26 (89.7%), 3 (10.3%), and 0 (0.0%) for lidocaine (p=0.008). CONCLUSIONS Ketorolac is a safe and more effective alternative to morphine derivatives for SWL analgesia. Lidocaine gel should not be used as mono-analgesia for SWL.
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A Single Preoperative Administration of Dexamethasone, Low-dose Pregabalin, or a Combination of the 2, in Spinal Surgery, Does Not Provide a Better Analgesia Than a Multimodal Analgesic Protocol Alone.
Momon, A, Verdier, B, Dolomie, JO, Gardette, M, Pereira, B, Curt, I, Dualé, C
The Clinical journal of pain. 2019;(7):594-601
Abstract
OBJECTIVES A single perioperative dose of glucocorticoid or gabapentinoid, or a combination of the 2, may improve postoperative analgesia, but data are still insufficient to be conclusive. In this single-center, randomized, double-blind, and double-dummy trial, we aimed to test whether the analgesic effect of adding preoperative pregabalin, at a dose unlikely to induce side effects, to preoperative dexamethasone improves early mobilization after spinal surgery. MATERIALS AND METHODS A total of 160 patients undergoing scheduled lumbar disk surgery (145 analyzed) comprised the study cohort. The patients received either 0.2 mg/kg intravenous dexamethasone before incision, or 150 mg oral pregabalin 1 hour before surgery, or a combination of the 2, or none of the above (control). Analgesia was supplemented by acetaminophen and ketoprofen, plus oxycodone ad libitum. The primary outcome was pain intensity during the first attempt to sit up, assessed the morning of the first postoperative day on an 11-point Numerical Rating Scale. Pain at rest and when standing up, opioid consumption, and tolerance were also assessed. RESULTS None of the treatments tested differed from the control group in terms of efficacy or tolerance, even 6 months after surgery. The overall quality of analgesia was good, with only 10% and 30% of pain scores exceeding 3/10 for pain at rest and during movement, respectively. DISCUSSION In this surgical model with the given anesthetic and analgesic environment, there was no advantage gained by adding low-dose pregabalin or dexamethasone. The multimodal analgesic protocol applied to all patients may have reduced the size of the effect.