Effective Painkillers Research Articles

SYNTHESIS AND BIOLOGICAL ACTIVITIES OF ACETAMINOPHEN AND IBUPROFEN METAL COMPLEXES OR DERIVATIVES: A REVIEW

We reviewed scientific literature on the synthesis of acetaminophen and ibuprofen, as well as their derivatives and biological properties. The synthesis of acetaminophen involves the acetylation of 4-aminophenol and acetic anhydride, while ibuprofen is synthesised by reacting isobutyl benzene and acetic anhydride in four continuous reaction stages, which are Friedel-Crafts acylation, carbonyl reduction, chloride substitution, and Grignard reaction. To obtain their derivatives, modifications have been made either by complexing the main structure of the drug compound with metal elements or adding certain desired moieties, such as thiourea, amide, ammonium, halogen, silicon, and 1,3,4-oxadiazole. Ibuprofen and acetaminophen have been recognised as effective painkillers and anti-inflammatories. Recently, their derivatives have been implicated in a variety of biological effects. The biological activities of acetaminophen and ibuprofen derivatives have been reported to exhibit urease inhibition and inflammatory inhibition, as well as inhibit the proliferation of breast cancer cells MCF-7. Overall, this review article describes the synthesis of acetaminophen and ibuprofen derivatives, complete with their biological activities such as antimicrobial, antifungal, anti-inflammatory, urease inhibitors, and anticancer.

Bioinspired composite packed in blunt needles, integrated microextraction and determination of oxycodone and naloxone in saliva by substrate spray mass spectrometry

BackgroundOpioids are effective painkillers used for medical purposes. Their prolonged ingestion can provoke some side effects (including overdose or constipation) that are minimized by using opioid antagonists (e.g., naloxone). The rapid determination of opioids and their antagonists in biosamples is essential for an effective medical treatment. The direct combination of sample preparation and mass spectrometry (MS) fits well in this scenario. It can speed up the analysis achieving a good selectivity, which relies on the sample preparation and MS, and sensitivity levels. ResultsThis article presents a novel substrate-spray mass spectrometry interface based on a polydopamine-cotton (PDA-Cel) composite hosted inside the inner diameter of a 14-gauge blunt needle to determine oxycodone and naloxone in saliva samples. The needle is used as a microextraction device and a substrate for mass spectrometric analysis. The lack of sharpness of the 14-gauge (14G) blunt needles challenges the formation of the electrospray (ESI), and a commercial 10 μL pipette tip is proposed as a simple solution to this shortcoming. Under the optimum parameters, the proposed method was validated, obtaining limits of detection lower than 0.6 μg L−1, linear range up to 200 μg L−1, and linearity better than 0.9915. Relative standard deviation (RSD) and relative recoveries (RR) were studied at three different concentration levels (2, 40, and 200 μg L−1). RSD values were better than 20.7 %, and RR ranged from 90 to 114 %. Finally, a positive sample from a patient under medical treatment was analyzed. Significance and novelty14G blunt needles have been demonstrated as effective extraction devices due to their low price (<0.15 € per extraction unit), their better safety (avoiding finger pricking), and their higher hosting capacity (up to 8 mg of sorbent). The conductivity of stainless steel permits their use as electrospray emitters, making their direct combination to MS easier. The large variety of fibrous sorbents makes this approach versatile enough to be adapted to other analytical problems.

Targeting TRPV1 for Cancer Pain Relief: Can It Work?

Chronic intractable pain affects a large proportion of cancer patients, especially those with metastatic bone disease. Blocking sensory afferents for cancer pain relief represents an attractive alternative to opioids and other drugs acting in the CNS in that sensory nerve blockers are not addictive and do not affect the mental state of the patient. A distinct subpopulation of sensory afferents expresses the capsaicin receptor TRPV1. Intrathecal resiniferatoxin, an ultrapotent capsaicin analog, ablates TRPV1-expressing nerve endings exposed to the cerebrospinal fluid, resulting in permanent analgesia in women with cervical cancer metastasis to the pelvic bone. High-dose capsaicin patches are effective pain killers in patients with chemotherapy-induced peripheral neuropathic pain. However, large gaps remain in our knowledge since the mechanisms by which cancer activates TRPV1 are essentially unknown. Most important, it is not clear whether or not sensory denervation mediated by TRPV1 agonists affects cancer progression. In a murine model of breast cancer, capsaicin desensitization was reported to accelerate progression. By contrast, desensitization mediated by resiniferatoxin was found to block melanoma growth. These observations imply that TRPV1 blockade for pain relief may be indicated for some cancers and contraindicated for others. In this review, we explore the current state of this field and compare the analgesic potential of TRPV1 antagonism and sensory afferent desensitization in cancer patients.

Targeting Members of the Chemokine Family as a Novel Approach to Treating Neuropathic Pain.

Neuropathic pain is a debilitating condition that affects millions of people worldwide. Numerous studies indicate that this type of pain is a chronic condition with a complex mechanism that tends to worsen over time, leading to a significant deterioration in patients' quality of life and issues like depression, disability, and disturbed sleep. Presently used analgesics are not effective enough in neuropathy treatment and may cause many side effects due to the high doses needed. In recent years, many researchers have pointed to the important role of chemokines not only in the development and maintenance of neuropathy but also in the effectiveness of analgesic drugs. Currently, approximately 50 chemokines are known to act through 20 different seven-transmembrane G-protein-coupled receptors located on the surface of neuronal, glial, and immune cells. Data from recent years clearly indicate that more chemokines than initially thought (CCL1/2/3/5/7/8/9/11, CXCL3/9/10/12/13/14/17; XCL1, CX3CL1) have pronociceptive properties; therefore, blocking their action by using neutralizing antibodies, inhibiting their synthesis, or blocking their receptors brings neuropathic pain relief. Several of them (CCL1/2/3/7/9/XCL1) have been shown to be able to reduce opioid drug effectiveness in neuropathy, and neutralizing antibodies against them can restore morphine and/or buprenorphine analgesia. The latest research provides irrefutable evidence that chemokine receptors are promising targets for pharmacotherapy; chemokine receptor antagonists can relieve pain of different etiologies, and most of them are able to enhance opioid analgesia, for example, the blockade of CCR1 (J113863), CCR2 (RS504393), CCR3 (SB328437), CCR4 (C021), CCR5 (maraviroc/AZD5672/TAK-220), CXCR2 (NVPCXCR220/SB225002), CXCR3 (NBI-74330/AMG487), CXCR4 (AMD3100/AMD3465), and XCR1 (vMIP-II). Recent research has shown that multitarget antagonists of chemokine receptors, such as CCR2/5 (cenicriviroc), CXCR1/2 (reparixin), and CCR2/CCR5/CCR8 (RAP-103), are also very effective painkillers. A multidirectional strategy based on the modulation of neuronal-glial-immune interactions by changing the activity of the chemokine family can significantly improve the quality of life of patients suffering from neuropathic pain. However, members of the chemokine family are still underestimated pharmacological targets for pain treatment. In this article, we review the literature and provide new insights into the role of chemokines and their receptors in neuropathic pain.

Treatment of acute and chronic cervical musculoskeletal pain

Pain in the cervical spine is a widespread condition that significantly disrupts the quality of life, often leads to disability and requires significant economic costs. The most common type of neck pain is nonspecific (vertebrogenic cervicalgia). The most frequent (in 36–67% of cases) anatomical source of nonspecific neck pain is considered to be the lesion of the intervertebral facet joints. Tests to determine the anatomical sources of nonspecific pain are unreliable, in addition, their detection does not significantly affect treatment. Degenerative changes of the spine are often detected during neuroimaging, depend on age, but do not correlate with clinical symptoms and severity of symptoms. In the absence of red flags of anxiety and negative results of neurological examination, neuroimaging or laboratory methods of research are not required. An assessment of prognostic factors is important. Factors contributing to chronization include: female sex, old age, high intensity of pain at the onset of the disease, the presence of psychosocial problems. Modern classifications, the basics of diagnosis, treatment and prevention of nonspecific neck pain are given. Modern effective methods of treatment are physical therapy, manual therapy and psychological programs, a multimodal approach to treatment is optimal. There is a very low level of evidence for electrotherapy, traction, laser therapy, acupuncture, dry needle treatment, thermal or cold procedures. The use of drug therapy is recommended, both separately and in combination with other methods of treatment. The most effective painkillers for neck pain are non-opioid analgesics – NSAIDs and paracetamol. The use of cervical orthosis is not recommended. Clinical cases of patients with acute and chronic nonspecific neck pain are described. The effectiveness of an integrated approach to the management of this category of patients, in accordance with modern recommendations, is shown. The treatment included drug and non-drug methods (therapeutic gymnastics, educational conversation). Dexketoprofen was used as pharmacotherapy according to a step-by-step regimen.

Cancer patients with chronic pain syndrome: can we improve their quality of life?

Many patients with different malignancies require analgesic therapy not only at advanced stages of the disease, but also during their diagnosis and treatment, as well as after treatment completion to ensure pain relief. New highly effective painkillers with a lower adverse event burden are critical to improve the quality of life of cancer patients with chronic pain syndrome. Tafalgin (tyrosyl-arginyl-phenylalanyl-glycinamide) is a highly specific μ1-opioid receptor agonist. It is an innovative Russian drug for subcutaneous administration, which has no analogues abroad. This article discusses the results of phase I–III clinical trials assessing tafalgin efficacy, safety, and potential to improve patients’ quality of life.

Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism: WLB-73502, an analgesic with improved efficacy and safety profile compared to strong opioids.

Opioids are the most effective painkillers, but their benefit-risk balance often hinder their therapeutic use. WLB-73502 is a dual, bispecific compound that binds sigma-1 (S1R) and mu-opioid (MOR) receptors. WLB-73502 is an antagonist at the S1R. It behaved as a partial MOR agonist at the G-protein pathway and produced no/unsignificant β-arrestin-2 recruitment, thus demonstrating low intrinsic efficacy on MOR at both signalling pathways. Despite its partial MOR agonism, WLB-73502 exerted full antinociceptive efficacy, with potency superior to morphine and similar to oxycodone against nociceptive, inflammatory and osteoarthritis pain, and superior to both morphine and oxycodone against neuropathic pain. WLB-73502 crosses the blood-brain barrier and binds brain S1R and MOR to an extent consistent with its antinociceptive effect. Contrary to morphine and oxycodone, tolerance to its antinociceptive effect did not develop after repeated 4-week administration. Also, contrary to opioid comparators, WLB-73502 did not inhibit gastrointestinal transit or respiratory function in rats at doses inducing full efficacy, and it was devoid of proemetic effect (retching and vomiting) in ferrets at potentially effective doses. WLB-73502 benefits from its bivalent S1R antagonist and partial MOR agonist nature to provide an improved antinociceptive and safety profile respect to strong opioid therapy.

Bifunctional μ opioid and σ1 receptor ligands as novel analgesics with reduced side effects.

Opioid analgesics are highly effective painkillers for the treatment of moderate or severe pain, but they are associated with a number of undesirable adverse effects, including the development of tolerance, addiction, constipation and life-threatening respiratory depression. The development of new and safer analgesics with innovative mechanisms of action, which can enhance the efficacy in comparison to available treatments and reduce their side effects, is urgently needed. The sigma-1 receptor (σ1R), a unique Ca2+-sensing chaperone protein, is expressed throughout pain-modulating tissues and affects neurotransmission by interacting with different protein partners, including molecular targets that participate in nociceptive signalling, such as the μ-opioid receptor (MOR), N-methyl-d-aspartate receptor (NMDAR) and cannabinoid 1 receptor (CB1R). Overwhelming pharmacological and genetic evidence indicates that σ1R antagonists induce anti-hypersensitive effects in sensitising pain conditions (e.g. chemically induced, inflammatory and neuropathic pain) and enhance opioid analgesia but not opioid-mediated detrimental effects. It has been suggested that balanced modulation of MORs and σ1Rs may improve both the therapeutic efficacy and safety of opioids. This review summarises the functional profiles of ligands with mixed MOR agonist and σ1R antagonist activities and highlights their therapeutic potentials for pain management. Dual MOR agonism/σ1R antagonism represents a promising avenue for the development of potent and safer analgesics.

Detection of Opioids on Mail/Packages Using Open Port Interface Mass Spectrometry (OPI-MS).

Opioids (and their more potent synthetic analogues) are used therapeutically as effective pain killers; however, recreational use and consequent overdoses are implicated in the deaths of thousands of people across the world annually. Trafficking of opioids and other illegal drugs through international mail has become a significant challenge for law enforcement personnel. Hundreds of millions of letters are sorted by the U.S. and Canadian postal services every day. Chemical analysis of this immense volume of mail requires a very fast sampling/detection method. This work explores the use of real-time mass spectrometry analysis with the recently developed Open Port Interface (OPI) for acoustically dispensed nanoliter volume sample droplets, a type of liquid microjunction surface sampling probe, for rapid and easy non-intrusive detection of fentanyl, heroin, and oxycodone. The OPI coupled to mass spectrometry is a novel sample introduction method that allows the rapid analysis of sample surfaces without preparation or modification. Opioids on different packaging materials (e.g., paper, bubble wrap, Ziploc bags) were rapidly (<10 s) interrogated by the OPI, and the sensitivities of the method compared. Furthermore, an opioid surrogate (caffeine) could be facilely detected on envelopes after processing through postal services.

TREK1 channel activation as a new analgesic strategy devoid of opioid adverse effects.

Opioids are effective painkillers. However, their risk-benefit ratio is dampened by numerous adverse effects and opioid misuse has led to a public health crisis. Safer alternatives are required, but isolating the antinociceptive effect of opioids from their adverse effects is a pharmacological challenge because activation of the μ opioid receptor triggers both the antinociceptive and adverse effects of opioids. The TREK1 potassium channel is activated downstream of μ receptor and involved in the antinociceptive activity of morphine but not in its adverse effects. Bypassing the μ opioid receptor to directly activate TREK1 could therefore be a safer analgesic strategy. We developed a selective TREK1 activator, RNE28, with antinociceptive activity in naive rodents and in models of inflammatory and neuropathic pain. This activity was lost in TREK1 knockout mice or wild-type mice treated with the TREK1 blocker spadin, showing that TREK1 is required for the antinociceptive activity of RNE28. RNE28 did not induce respiratory depression, constipation, rewarding effects, or sedation at the analgesic doses tested. This proof-of-concept study shows that TREK1 activators could constitute a novel class of painkillers, inspired by the mechanism of action of opioids but devoid of their adverse effects.

COMPARATIVE STUDY ON THE USING OF THE ORIGINAL VS GENERIC BALANCED COX-1,2 INHIBITORS IN THYROID SURGERY

Background. Recently balanced analgesia (BA) has become the standard for postoperative (post-op) pain management. One of the most effective painkillers are ketoprofen and its derivatives, including dexketoprofen. Discussions on the clinical efficacy of generic drugs over the original molecules continue quite lively, especially, over cheaper generic drugs. But no direct clinical studies to compare original vs generic dexketoprofen molecules in clinical practice were found.The Goal of Study. To investigate the therapeutic efficacy and safety of the use of original vs generic dexketoprofen in the complex of BA in patients with thyroidectomy. To assess a pharmacoeconomic comparison of the use of different dexketoprofen molecules.Materials and Methods. 440 patients with thyrotoxicosis syndrome were examined and then thyroidectomy was performed. 56 patients, who met the including/excluding criteria, were included in double-blinded study. By the method of adaptive randomization, patients were split on two groups: group D (n=27), who received original dexketoprofen (Dexalgin inject) and group S (n=29), who received generic dexketoprofen (Sertofen) from EU country. Complex BA included IV bolus dexketoprofen (DEX) 50 mg, IV lidocaine 1 mg/kg, IV dexamethasone 8 mg and bilateral blockade of superficial cervical plexus (BBSCP) by 0,5% bupivacaine 75-100 mg was used as pre-emptive analgesia 30 minutes before surgery in both groups. Maintenance anaesthesia was done by sevoflurane. According to study design in post-op preventive analgesia was done by DEX 50 mg every 8 hours (h) together with paracetamol (PAR) 1 g IV in the first 6h and following by oral 500 mg every 8 h. 100 mm NRS score was used for pain control. The laboratory markers of post-op stress (LMPOS), such as cortisol (CORT), prostaglandin E2 (PG E2), glucose (GLU) with NRS also were measured.Results and Discussion. Gender distribution: women were 21 (88,9%) and 25 (86,2 %) respectively in group D and group S (not statistically differences, NS). Average age was 48,7±2,3 in group D and 49,6±2,5 in group S (NS). No differences were found between both groups according to ASA physical status score. Duration of surgery and anesthesia were 63,6±3,4 min and 84,7±3,7 min in group D, in group S these indicators were 62,9±3,9 min and 83,5±4,1 min respectively. Pain level according to NRS after 3h, 6h, 12h, 24 h was 18,9 ± 1,4 mm, 23,1 ± 1,7 mm, 24,1 ± 1,8 mm і 20,2 ± 1,2 mm respectively and was assessed as weak in group D. In group S according to NRS after 3h, 6h, 12h, 24 h pain level was 19,1 ± 1,6 mm, 23,1 ± 1,7 mm, 23,9 ± 1,9 mm і 20,3 ± 1,4 mm. Statistically difference (p<0,05, Wilcoxon test) was noted between all check-points in comparison with previous pain level by NRS, however no difference found between groups. Nobody needed more PAR doses or an addition of morphine. Dynamics of LMPOS were as follows: an increase in the GLU was noted at the end of operation in 6,2% (group D) and 7,3% (group S) (difference NS) due to surgical aggression and dexamethasone usage in the BA complex. CORT level was grown before premedication from 387,9 ± 21,2 nmol/l to 406,5 ± 36,1 nmol/l at the end of operation in group D, in group S from 390,7 ± 24,5 nmol/l to 410,3 ± 38,1 nmol/l respectively. No statistically difference was noted between groups neither before nor after the operation. However, after 24 hours CORT level was broken down till 38,4 ± 7,8 nmol/l (group D) and 41,1 ± 8,1 nmol/l (group S) (glucocorticosteroid suppression by dexamethasone). PG E2 level decreased from 281,2 ± 43,6 pg/ml till 192,1 ± 38,2 pg/ml after 24 hours in group D (p=0,018), from 288,5 ± 41,5 pg/ml till 186,8 ± 41,3 pg/ml in group S respectively without statistically differences between groups. No major bleeding complication were found in both groups, 2 cases in each group were erythematosis gastritis and erosis gastropathy. Safety level complex BA was assessed in 92,6% (group D) and 93,1% in group S (р=0,941, NS). Pharmacoeconomic analysis was shown, that using original DEX in scheme BA was more expensive by 48,2% (+additionally 58, 24 UAH per patient) vs generic DEX origin EU country.Conclusions. In double-blind randomized study has shown the therapeutic equivalence of the generic dexketoprofen solution for injection to the original drug according to the NRS and the dynamics of LMPOS. High safety of use of dexketoprofen in the complex of balanced multimodal analgesia was established. No found significant difference between groups for efficacy and safety. Pharmacoeconomic analysis has shown that the use of generic drug dexketoprofen with confirmed clinically therapeutic equivalence has significant advantages.

Lessons on lymphangioleiomyomatosis: positivity and possibilities

Lessons on lymphangioleiomyomatosis: positivity and possibilities

BPR1M97, a dual mu opioid receptor/nociceptin-orphanin FQ peptide receptor agonist, produces potent antinociceptive effects with safer properties than morphine

There is unmet need to design an analgesic with fewer side effects for severe pain management. Although traditional opioids are the most effective painkillers, they are accompanied by severe adverse responses, such as respiratory depression, constipation symptoms, tolerance, withdrawal, and addiction. We indicated BPR1M97 as a dual mu opioid receptor (MOP)/nociceptin-orphanin FQ peptide (NOP) receptor full agonist and investigated the pharmacology of BPR1M97 in multiple animal models. In vitro studies on BPR1M97 were assessed using cyclic-adenosine monophosphate production, β-arrestin, internalization, and membrane potential assays. In vivo studies were characterized using the tail-flick, tail-clip, lung functional, heart functional, acetone drop, von Frey hair, charcoal meal, glass bead, locomotor activity, conditioned place preference (CPP) and naloxone precipitation tests. BPR1M97 elicited full agonist properties for all cell-based assays tested in MOP-expressing cells. However, it acted as a G protein-biased agonist for NOP. BPR1M97 initiated faster antinociceptive effects at 10 min after subcutaneous injection and elicited better analgesia in cancer-induced pain than morphine. Unlike morphine, BPR1M97 caused less respiratory, cardiovascular, and gastrointestinal dysfunction. In addition, BPR1M97 decreased global activity and induced less withdrawal jumping precipitated by naloxone. Thus, BPR1M97 could serve as a novel small molecule dual receptor agonist for antinociception with fewer side effects than morphine.This article is part of the Special Issue entitled ‘New Vistas in Opioid Pharmacology’.

Використання Тантум Верде® в лікуванні хронічної механічної травми слизової оболонки порожнини рота

Actuality. In the treatment of erosive-ulcerative lesions of oral mucous membrane, caused by chronic mechanical trauma, it is reasonable to use the agents of complex action which would produce a local anti-inflammatory effect and reduce mucosal pain, and would have antiseptic and antimicrobial properties. One of them is Tantum Verde®, a local non-steroidal drug based on benzidamine hydrochloride.The aim of the research was to evaluate the effectiveness of the use of the preparation «Tantum Verde®» in the local treatment of erosive-ulcerative lesions of the oral mucous membrane caused by chronic mechanical trauma.Results of the research. There were treated 30 patients aged 18–58 with erosive-ulcerative lesions of oral mucous membrane, caused by chronic mechanical trauma of orthopedic structures or orthodontic devices. It was noted that 6 patients with removable prostheses had the growth of mucous membrane in areas of contact with the edges of the prosthesis. Among 15 patients from the experimental group, the preparation «Tantum Verde®» was additionally used. Absence or significant reduction of clinical signs of erosive-ulcerative lesions caused by mechanical trauma of orthopedic structures or orthodontic devices occurred 1–1,5 days earlier among the patients of experimental group. It is noted the positive effect of Tantum Verde® on pain reduction, hygienic condition, improvement of tissue trofics and healing of mucous membrane areas after surgical removal of prosthetic granulomas.Conclusions. The preparation «Tantum Verde®» is an effective painkiller that accelerates the disappearance of inflammatory signs, improves trophics, accelerates healing and epithelization of defects at patients with erosive-ulcerative lesions of oral mucous membrane, caused by chronic mechanical trauma with dental prostheses and non-removable orthodontic devices. It weakens the reactive inflammatory reaction of tissues to surgery after prosthetic granulomas removal, improves hygiene, accelerates healing and suture removal for 1–1,5 days.Keywords: «Tantum Verde®», chronic mechanical trauma of oral mucous membrane, erosive-ulcerative lesions, local treatment.

Opioids: From Being a Doctor to Being a Patient.

Opioids: From Being a Doctor to Being a Patient.

Failure to Find a Conditioned Placebo Analgesic Response.

Background: Associative learning has, in several studies, been modulated by the sex of the participant. Consistent with this, a recent review found that conditioned nocebo effects are stronger in females than in males.Purpose: It has been suggested that conditioned placebo responses are stronger in females, and this hypothesis was investigated in the present study. Cortisol and measures of negative emotions were taken to investigate if these processes could mediate any conditioned placebo effects.Methods: Cold pain was applied to the volar forearm. The Conditioned group received inert capsules prior to two presentations of less painful stimulations, to associate intake of the capsules with reduced pain. The pain control group received the same painful stimulation as the Conditioned group, but no capsules. The Capsule control group received the capsules in the same way as the Conditioned group, but no decrease in the painful stimulation. Participant sex was crossed across groups. It was hypothesized that in the Conditioned group, an expectation of reduced pain should be induced after administration of the capsules, and this should generate placebo analgesia, and mostly so in females.Results: The Conditioned group reported lower pain during conditioning, and rated the capsules as more effective painkillers than the capsule control group. However, placebo analgesia was not reliably observed in the Conditioned group.Conclusion: The placebo capsules were rated as effective painkillers, but this did not translate into a placebo analgesic effect. This could be due to violation of response expectancies, too few conditioning trials, and differences in pain ratings in the pre-test that could be due to previous experience with painkillers.

Acetaminophen loaded nanofibers as a potential contact layer for pain management in Burn wounds

Application of drugs at local site is beneficial with less side effects. This study dealt with the development of nanofibers (NFs) based drug delivery system for local pain management in burn wounds with acetaminophen as model drug which has been proven to be an effective pain killer in mid to moderate burn wounds. The electrospinning process parameters were optimized by using Taguchi method. The optimized NFs were then selected for further characterization i.e. Fourier Transform Infra-Red Spectroscopy (FTIR), Scanning Electron Microscope (SEM), x-ray Diffraction (XRD) and Differential Scanning Calorimetry (DSC). The NFs final diameter varied from 185 to 375 nm. The optimized NFs showed good liquid absorption properties (∼11 g g−1) with fast release of drug (∼80% in 60 min). The equilibrium drug release data was best followed by Ritger-Peppas kinetic model and showed case II transport mechanism. FTIR analysis confirmed that the drug was successfully incorporated within the NFs. DSC and XRD confirmed that the addition of drug increased the crystallinity of NFs but reduced the liquid absorption to some extent. The desired fast drug delivery along with good liquid absorption and moist environment of the fabricated NFs could be promising solution to manage pain in burn wounds at local site.

Evaluation of the effectiveness and efficiency of the triage emergency department nursing protocol for the management of pain.

IntroductionPain is a common symptom presented in the emergency department (ED) although it is often underestimated, poorly evaluated and treated. The application of a protocol for timely pain management ensured by the nurse can avoid the delays in the analgesic treatment and improve the patient’s quality of waiting.AimsTo check the effectiveness and efficiency of the protocol aimed at early pain management in triage, active in our ED. In particular, the response to analgesic treatment was evaluated 60 minutes after the administration and at discharge. Patient satisfaction was also evaluated using two anonymous questionnaires both at discharge and 48 hours later via telephone.MethodsA single-center, observational study was conducted on a prospective cohort of patients (aged ≥4 years) with a pain symptom at admission in ED with no surgical picture.ResultsIn the observation period (June 2015–May 2016), 382 patients were enrolled, and of these, 312 (84.8%) accepted pain therapy during triage stage in the ED. In 97.4% of the cases, orosoluble paracetamol 1000 mg was administered. In the re-evaluation done 60 minutes later, 65.9% of the patients showed a reduction of at least 2 points on Numeric Rating Scale (NRS), equal to a mean reduction of 2.24 points (95% CI: 2.03–2.45). The mean time of analgesia intake was equal to 5.9 minutes (95% CI: 3.8–8.1). In the re-evaluation done at discharge, 33.2% of the patients showed a reduction of NRS score >50%, leading to a mean reduction of 39% (95% CI: 35.3%−41.9%). The level of patient satisfaction was high with a mean value >9 points (maximum satisfaction =10).ConclusionThis protocol shows that optimal pain management was achieved by patients rapidly receiving an effective painkiller therapy at triage, leading to substantial patient satisfaction. In moderate pain, orosoluble paracetamol 1000 mg provided a reduction of NRS score by 2 points in 67.6% of the patients, confirming to be the analgesic of choice in ED.

A nontoxic pain killer designed by modeling of pathological receptor conformations.

Indiscriminate activation of opioid receptors provides pain relief but also severe central and intestinal side effects. We hypothesized that exploiting pathological (rather than physiological) conformation dynamics of opioid receptor-ligand interactions might yield ligands without adverse actions. By computer simulations at low pH, a hallmark of injured tissue, we designed an agonist that, because of its low acid dissociation constant, selectively activates peripheral μ-opioid receptors at the source of pain generation. Unlike the conventional opioid fentanyl, this agonist showed pH-sensitive binding, heterotrimeric guanine nucleotide-binding protein (G protein) subunit dissociation by fluorescence resonance energy transfer, and adenosine 3',5'-monophosphate inhibition in vitro. It produced injury-restricted analgesia in rats with different types of inflammatory pain without exhibiting respiratory depression, sedation, constipation, or addiction potential.

Use of Chronic Methadone Before Total Knee Arthroplasty

BackgroundA subset of patients who undergo total knee arthroplasty (TKA) are on methadone maintenance. They require more and often unpredictable quantities of opioids to function as effective painkillers. This study aims to compare the opioid requirements and the immediate postoperative course for patients on methadone maintenance with those who are not, after a TKA. MethodsA retrospective, case-control study was performed. From 2005 to 2010, 36 patients, who underwent a unilateral TKA, on chronic methadone maintenance were identified. A control group matched for age, gender, and body mass index comprised patients from the same period, who did not self-report taking methadone. Chart review and analysis of patient demographics, type of anesthesia used, preoperative methadone use, inpatient opioid use (converted to oral morphine equivalent doses), need for in-house pain management consult, length of hospital stay, and need for reoperation were performed. ResultsPatients on chronic methadone maintenance used significantly more opioids than patients not on methadone during their entire inpatient stay (P < .001). This was demonstrated by a higher median daily usage of opioids and higher patient-controlled analgesia usage. Patients on methadone maintenance had a significantly longer postoperative inpatient hospitalization (P < .001). Finally, these patients required significantly more inpatient pain management referrals (P = .025). ConclusionThere is a significantly higher opioid requirement, length of stay, and pain management consults in patients on methadone maintenance compared with those who are not after a TKA. These patients may benefit from a nonroutine approach to perioperative care in TKA.