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Comparing Intradermal Sterile Water with Intravenous Morphine in Reducing Pain in Patients with Renal Colic: A Double-Blind Randomized Clinical Trial.
Mozafari, J, Verki, MM, Tirandaz, F, Mahjouri, R
Reviews on recent clinical trials. 2020;(1):76-82
Abstract
OBJECTIVE The present study was conducted to investigate the effect of intradermal administration of sterile water compared to intravenous morphine on patients with renal colic. METHODS This double-blind, randomized clinical trial study was conducted in 2017 to compare the therapeutic effects of intradermal sterile water with those of intravenous morphine on patients with renal colic presenting to the emergency departments (ED) of Imam Khomeini and Golestan Hospitals in Ahvaz, Iran. The first group received 0.5 ml of intradermal sterile water, and the second group 0.1mg/kg of intravenous morphine plus 0.5 ml of intradermal sterile water in the most painful area or the center of the painful area in the flank. The pain severity was measured using a visual analogue scale (VAS), and the medication side-effects were recorded at the beginning of the study and minutes 15, 30,45 and 60. RESULTS A total of 94 patients were studied in two groups. The mean severity of pain was 2.97 ± 1.51 in the sterile water group and 2.34 ± 1.89 in the morphine group at minute 30 (P=0.042), 2.58 ± 1.43 in the sterile water group and 1 ± 1.23 in the morphine group at minute 45 (P<0.001), and 1.89 ± 1.7 in the sterile water group and 0.52 ± 0.79 in the morphine group at minute 60 (P<0.001). CONCLUSION Morphine reduces pain faster and more effectively than intradermal sterile water; nevertheless, treatment with intradermal sterile water can be used as an appropriate surrogate or adjunct therapy for pain control, particularly in special patients or in case of medication scarcity.
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Prospective randomized trial of interventions for vincristine-related neuropathic pain.
Anghelescu, DL, Tesney, JM, Jeha, S, Wright, BB, Trujillo, L, Sandlund, JT, Pauley, J, Cheng, C, Pei, D, Pui, CH
Pediatric blood & cancer. 2020;(9):e28539
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Abstract
BACKGROUND To evaluate the efficacy of gabapentin at 20 mg/kg per day in the treatment of vincristine-related neuropathic pain. PROCEDURE Children aged 1-18 years who developed vincristine-induced neuropathy on a St Jude frontline acute lymphoblastic leukemia trial were prospectively enrolled on a randomized, double-blind, placebo-controlled, phase II trial with two treatment arms: gabapentin plus opioid versus placebo plus opioid. Daily evaluations of morphine dose (mg/kg per day) and pain scores were conducted for up to 21 days; the values of the two arms were compared to assess analgesic efficacy. RESULTS Of 51 study participants, 49 were eligible for analyses. Twenty-five participants were treated with gabapentin, with a mean (SD) dose of 17.97 (2.76) mg/kg per day (median 18.26, range 6.82-21.37). The mean (SD) opioid doses taken, expressed as morphine equivalent daily (mg/kg per day), were 0.26 (0.43) in the gabapentin group (25 patients, 432 days) and 0.15 (0.22) in the placebo group (24 patients, 411 days; P = .15). Only the risk classification of acute lymphoblastic leukemia was significantly associated with the daily morphine dosage (P = .0178): patients in the lower risk arm received higher daily morphine dosages. Multivariate analyses revealed a significant difference between the groups' average daily scores for the previous 24 h and "right now." CONCLUSION In this population of children with vincristine-related neuropathic pain, opioid consumption and pain scores were higher in the gabapentin group than in the placebo group. Future randomized, double-blind, placebo-controlled studies should test gabapentin given longer or at a higher dose.
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Breakthrough pain in patients with head & neck cancer. A secondary analysis of IOPS MS study.
Mercadante, S, Masedu, F, Valenti, M, Aielli, F
Oral oncology. 2019;:87-90
Abstract
AIM: To characterize breakthrough pain (BTcP) in patients with Head and neck (H&N) cancer. METHODS This was a secondary analysis of multicenter study of BTcP. Background pain intensity and opioid dose were recorded. The number of BTcP episodes, their intensity, predictability, onset, duration and interference with daily activities were collected. Opioids used for BTcP, and the mean time to meaningful pain relief after taking medication, were assessed. The presence of mucositis was also assessed. RESULTS 205 patients with H&N cancer were examined. The mean number of BTcP episodes was 2.8/day, which was higher than in general population. The mean intensity of BTcP was 7.4. BTcP was more predictable in H&N cancer than in other tumors. The main trigger of predictable BTcP was the ingestion of food (76.5%). BTcP onset was fast in 148 patients (72.2%). The mean time to meaningful pain relief after taking a BTcP medication was 15.3 min and BTcP interference with daily activity was relevant in most patients (89.2%). Transdermal drugs and nasal fentanyl preparations were more frequently used for background pain and BTcP, respectively. A consistent number of patients with H&N cancer (38.5%) exhibited different levels of oral mucositis. CONCLUSION BTcP in patients with H&N cancer is characterized by a larger number of episodes/day and the predictability, particularly with ingestion of food. The use of drugs for background analgesia and BTcP were conditioned by the possible interference with swallowing or local mucosal damage.
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Comparing the Efficacy of Peritonsillar Injection of Tramadol With Honey in Controlling Post-Tonsillectomy Pain in Adults.
Hatami, M, Mirjalili, M, Ayatollahi, V, Vaziribozorg, S, Zand, V
The Journal of craniofacial surgery. 2018;(4):e384-e387
Abstract
INTRODUCTION The authors investigated the effect of honey on post-tonsillectomy pain and compare its efficacy with tramadol. METHODS This clinical trial was performed on 60 patients with American Society of Anesthesia I and II aged between 18 and 55 years and underwent tonsillectomy. Induction of anesthesia was carried out using 2 mg/kg propofol and 0.5 atracurium following 1.5 μg/kg fentanyl administration. Group B was given tramadol at dose of 2 mg/kg and with volume of 4 mL and Group A was given normal saline with the same volume 2 mL of medications were injected using needle (25) into tonsil bed and anterior old of each tonsil by an anesthesiologist. Three minutes after injection, the surgery was performed by the same ENT residents for all patients. In the recovery room Group B received antibiotics and oral acetaminophen. Group A was given antibiotics, oral acetaminophen, and honey dissolved in 40 mL warm water every 6 hours from when the patient was fully awake. Patients in Group A were told to eat honey 3 times a day 7 days postoperatively. Pain was scored using Numeric Rating Scale at the time points of 2, 6, 12, and 24 hours as well as 3 and 7 days postoperatively. Moreover, the healing status and epithelialization degree of tonsillar bed were considered on 1 and 7 days after the surgery by ENT specialist. RESULTS The mean of pain score was significantly higher in Group A within 24 hours postoperatively as compared with Group B (P < 0.01). The mean of pain score was lower in Group B after 3 and 7 days but this difference was not statistically significant (P > 0.05). Considering restoration status and epithelialization degree of tonsillar bed on the 1st and 7th days, there was no statistically significant difference between 2 groups; however, tonsillar bed healing process was better in Group B on the 7th day. CONCLUSION The current investigation confirmed the positive impact of tramadol on post-tonsillectomy pain relief in adults. The authors also found that honey can be used as a complementary treatment along with acetaminophen and other analgesics for reducing post-tonsillectomy pain. Considering honey impact on wound healing and its anti-inflammatory effect, it is suggested for relieving complications after surgery.
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Randomized open-label phase II study comparing oxycodone-naloxone with oxycodone in early return of gastrointestinal function after laparoscopic colorectal surgery.
Creamer, F, Balfour, A, Nimmo, S, Foo, I, Norrie, JD, Williams, LJ, Fearon, KC, Paterson, HM
The British journal of surgery. 2017;(1):42-51
Abstract
BACKGROUND Combined oral modified-release oxycodone-naloxone may reduce opioid-induced postoperative gut dysfunction. This study examined the feasibility of a randomized trial of oxycodone-naloxone within the context of enhanced recovery for laparoscopic colorectal resection. METHODS In a single-centre open-label phase II feasibility study, patients received analgesia based on either oxycodone-naloxone or oxycodone. Primary endpoints were recruitment, retention and protocol compliance. Secondary endpoints included a composite endpoint of gut function (tolerance of solid food, low nausea/vomiting score, passage of flatus or faeces). RESULTS Eighty-two patients were screened and 62 randomized (76 per cent); the attrition rate was 19 per cent (12 of 62), leaving 50 patients who received the allocated intervention with 100 per cent follow-up and retention (modified intention-to-treat cohort). Protocol compliance was more than 90 per cent. Return of gut function by day 3 was similar in the two groups: 13 (48 per cent) of 27 in the oxycodone-naloxone group and 15 (65 per cent) of 23 in the control group (95 per cent c.i. for difference -10·0 to 40·7 per cent; P = 0·264). However, patients in the oxycodone-naloxone group had a shorter time to first bowel movement (mean(s.d.) 87(38) h versus 111(37) h in the control group; 95 per cent c.i. for difference 2·3 to 45·4 h, P = 0·031) and reduced total (oral plus parenteral) opioid consumption (mean(s.d.) 78(36) versus 94(56) mg respectively; 95 per cent c.i. for difference -10·2 to 42·8 mg, P = 0·222). CONCLUSION High participation, retention and protocol compliance confirmed feasibility. Potential benefits of oxycodone-naloxone in reducing time to bowel movement and total opioid consumption could be tested in a randomized trial. Registration number: NCT02109640 (https://www.clinicaltrials.gov/).
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The effect of toothpicks containing flavoring and flavoring plus jambu extract (spilanthol) to promote salivation in patients -diagnosed with opioid-induced dry mouth (xerostomia).
Davis, B, Davis, K, Bigelow, S, Healey, P
Journal of opioid management. 2017;(5):335-340
Abstract
OBJECTIVE To determine if the use of toothpicks infused with flavoring and flavoring plus the food additive spilanthol (Xerosticks™) improve saliva flow in people with opioid-induced dry mouth. DESIGN Time series, nonrandomized, double-blind within-subject design. SETTING Private practice/academic multidisciplinary pain and palliative care clinic. PARTICIPANTS Ten subjects with opioid-induced dry mouth were recruited, and all finished the study. METHODS Salivary flow and pH were measured consecutively at baseline, following use of a mango-flavored toothpick, and again after use of a mango-flavored toothpick infused with spilanthol. Salivary flow rates and saliva pH were compared between flavored and baseline, between flavored + spilanthol and baseline, and between the flavored and flavored + spilanthol. Mouthfeel of each toothpick was assessed using the Bluestone Mouthfeel Questionnaire. OUTCOMES The primary measure was salivary flow, and the secondary measures were salivary pH and mouthfeel. RESULTS Saliva flow increased 440 percent over baseline with use of a flavored toothpick and 628 percent over baseline with similarly flavored toothpicks infused with spilanthol, and these differences are significant (p = 0.00002). Saliva pH increased with both toothpicks (p = 0.04). The addition of spilanthol produced a greater increase in salivary flow (p = 0.05) compared to control toothpicks with flavoring alone. Furthermore, addition of spilanthol improved the "mouthfeel" of the toothpick (p = 0.00001). CONCLUSIONS Toothpicks infused with either flavoring or flavoring plus spilanthol are likely to be an effective remedy for opioid-induced dry mouth. Addition of spilanthol may improve effectiveness over flavoring alone and may be better ac-cepted because spilanthol appears to improve mouthfeel.
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Dexketoprofen/tramadol: randomised double-blind trial and confirmation of empirical theory of combination analgesics in acute pain.
Moore, RA, Gay-Escoda, C, Figueiredo, R, Tóth-Bagi, Z, Dietrich, T, Milleri, S, Torres-Lagares, D, Hill, CM, García-García, A, Coulthard, P, et al
The journal of headache and pain. 2015;:541
Abstract
BACKGROUND Combination analgesics are effective in acute pain, and a theoretical framework predicts efficacy for combinations. The combination of dexketoprofen and tramadol is untested, but predicted to be highly effective. METHODS This was a randomised, double-blind, double-dummy, parallel-group, placebo-controlled, single-dose trial in patients with moderate or severe pain following third molar extraction. There were ten treatment arms, including dexketoprofen trometamol (12.5 mg and 25 mg) and tramadol hydrochloride (37.5 mg and 75 mg), given as four different fixed combinations and single components, with ibuprofen 400 mg as active control as well as a placebo control. The study objective was to evaluate the superior analgesic efficacy and safety of each combination and each single agent versus placebo. The primary outcome was the proportion of patients with at least 50 % max TOTPAR over six hours. RESULTS 606 patients were randomised and provided at least one post-dose assessment. All combinations were significantly better than placebo. The highest percentage of responders (72%) was achieved in the dexketoprofen trometamol 25 mg plus tramadol hydrochloride 75 mg group (NNT 1.6, 95% confidence interval 1.3 to 2.1). Addition of tramadol to dexketoprofen resulted in greater peak pain relief and greater pain relief over the longer term, particularly at times longer than six hours (median duration of 8.1 h). Adverse events were unremarkable. CONCLUSIONS Dexketoprofen trometamol 25 mg combined with tramadol hydrochloride 75 mg provided good analgesia with rapid onset and long duration in a model of moderate to severe pain. The results of the dose finding study are consistent with pre-trial calculations based on empirical formulae. TRIAL REGISTRATION EudraCT (2010-022798-32); Clinicaltrials.gov (NCT01307020).
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Catechol-O-methyltransferase genotype modulates opioid release in decision circuitry.
Mitchell, JM, O'Neil, JP, Jagust, WJ, Fields, HL
Clinical and translational science. 2013;(5):400-3
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Impulsivity, a risk factor for substance abuse disorders, is modulated by the Val158 variant of the catechol-O-methyltransferase (COMT) gene. Rodent studies have shown that opioids enhance impulsivity. Furthermore, alcohol consumption leads to endogenous opioid release in the cortex and nucleus accumbens (NAc), and this opioid release is correlated with greater positive hedonic effect. Using the selective mu opioid receptor radioligand [¹¹C] carfentanil, we find that, following alcohol consumption, individuals with the COMT Val158 allele have greater opioid release in the right NAc but less release in medial orbital frontal cortex (OFC). These data suggest that genetic regulation of dopamine levels can affect alcohol consumption in part by modulating endogenous opioid release in specific brain regions implicated in reward, which in turn promotes impulsive choice.
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Topical fentanyl in a randomized, double-blind study in patients with corneal damage.
Zöllner, C, Mousa, S, Klinger, A, Förster, M, Schäfer, M
The Clinical journal of pain. 2008;(8):690-6
Abstract
OBJECTIVES Corneal damage causes severe pain. This study investigated whether peripheral opioid receptors are present in the human cornea and assessed the efficacy of topical fentanyl in patients with corneal erosion. METHODS Immunohistochemical staining experiments were performed to examine the presence of both mu and delta-receptors on peripheral nerve fibers within human corneal tissue. In a randomized, double-blind clinical trial dexpanthenol (n=20) or dexpanthenol plus 10 microg fentanyl (n=20) were topically applied every 4 hours to the eye of patients with a surgical intervention of corneal damage and subjective pain intensity was determined by a numerical rating scale. RESULTS Immunohistochemical staining identified peripheral nerve fibers in human cornea expressing both mu and delta-opioid receptors. In patients with corneal damage the ophthalmic intervention in local anesthesia decreased the subjective pain intensity significantly. At 4-hour intervals after the ophthalmic intervention, moderate pain intensity levels were not altered by the application of dexpanthenol with or without fentanyl. At 24 hours pain intensity dropped significantly, most likely owing to a natural decrease in pain, because the erosion was almost healed. DISCUSSION Both mu and delta-receptors are localized on nerve fibers within the cornea, which are accessible for topical opioid treatment. However, our formulation and dose of topical fentanyl in combination with dexpanthenol did not show any benefit in relieving pain from corneal erosion. Future studies are planned to determine the optimal protocol and dose of topical opioid treatment.
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Imaging human cerebral pain modulation by dose-dependent opioid analgesia: a positron emission tomography activation study using remifentanil.
Wagner, KJ, Sprenger, T, Kochs, EF, Tölle, TR, Valet, M, Willoch, F
Anesthesiology. 2007;(3):548-56
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BACKGROUND Previous imaging studies have demonstrated a number of cortical and subcortical brain structures to be activated during noxious stimulation and infusion of narcotic analgesics. This study used O-water and positron emission tomography to investigate dose-dependent effects of the short-acting mu-selective opioid agonist remifentanil on regional cerebral blood flow during experimentally induced painful heat stimulation in healthy male volunteers. METHODS Positron emission tomography measurements were performed with injection of 7 mCi O-water during nonpainful heat and painful heat stimulation of the volar forearm. Three experimental conditions were used during both sensory stimuli: saline, 0.05 microg x kg x min remifentanil, and 0.15 microg x kg x min remifentanil. Cardiovascular and respiratory parameters were monitored noninvasively. Across the three conditions, dose-dependent effects of remifentanil on regional cerebral blood flow were analyzed on a pixel-wise basis using a statistical parametric mapping approach. RESULTS During saline infusion, regional cerebral blood flow increased in response to noxious thermal stimulation in a number of brain regions as previously reported. There was a reduction in pain-related activations with increasing doses of remifentanil in the thalamus, insula, and anterior and posterior cingulate cortex. Increasing activation occurred in the cingulofrontal cortex (including the perigenual anterior cingulate cortex) and the periaqueductal gray. CONCLUSIONS Remifentanil induced regional cerebral blood flow increases in the cingulofrontal cortex and periaqueductal gray during pain stimulation, indicating that mu-opioidergic activation modulates activity in pain inhibitory circuitries. This provides direct evidence that opioidergic analgesia is mediated by activation of established descending antinociceptive pathways.