Acute Pain Therapy Research Articles

(290) - A novel targeted local analgesia platform to mitigate neuroinflammation and promote neuroregeneration

The management of acute neuropathic pain (ANP) remains a significant therapeutic challenge. Drug delivery targeted directly to the area of neuroinflammation in ANP could allow timely, site-specific therapeutic interventions with minimized systemic and off-target side effects. Our goal was the design, development, in vitro validation and pilot in vivo assessment of a new Theranostic Analgesic Regenerative Gel-Emulsion Technology (TARGET) platform for local anti-inflammatory drug delivery. The TARGET platform is biocompatible, thermoresponsive nanoemulgel laden with NIRF labelled theranostic nanoemulsions designed for macrophage targeted drug delivery of COX-2 inhibitors. Given their established pathogenic role in neuroinflammation, macrophages are critical cellular targets for therapy in both acute and chronic pain. Furthermore, modulation of macrophage behaviour with intracellular delivery of a COX-2 inhibitor in the context of neuronal injury can enhance neuroregeneration through stimulation of the M2 phenotype. Integration of dual therapeutic and diagnostic functions in a single local delivery platform provides an imaging signature of the underlying pathology, delivers a therapeutic agent (COX-2 inhibitor), and allows for monitoring drug delivery and therapeutic efficacy by live NIRF imaging. The TARGET platform represents a theranostic nanoemulgel which incorporates a triphasic perfluoropolyether (PFPE) nanoemulsion into a thermoresponsive hydrogel matrix. The nanoemulgel material is designed to flow at temperatures up to 90°F while gelling at body temperature to facilitate extended drug release for up to 30 days. Nanoemulsions incorporated into the hydrogel retain their size, shape and drug loading/release properties. We present in vitro characterization, product quality assessment and pharmacological validation and demonstrate in vivo efficacy in pilot testing in rat models of neuronal injury supported by behaviour assays and NIRF imaging. To the best of our knowledge, the TARGET platform represents the first paradigm of site specific analgesia with COX-2 inhibitors designed to augment neuroregeneration and suppress neuroinflammation in cell targeted manner.

Opiate & Benzodiazepine Confirmations: To Hydrolyze or Not to Hydrolyze is the Question.

Opiates/opioids and benzodiazepines are commonly prescribed drug therapies for acute and chronic pain. Urine drug testing is often employed to assess adherence to these mediations. Opioids and benzodiazepines are drug classes that undergo extensive metabolism through glucuronidation/sulfation. Conjugated glucuronide and sulfate drug metabolites can be difficult to detect by immunoassay and mass spectrometry methods. Consequently, false-negative or false-positive results can have a damaging impact on patient care. A common dilemma among drug-testing laboratories is whether to perform preanalytical hydrolysis to increase detection of drugs that are highly conjugated as metabolites. The purpose of hydrolysis is to cleave the glucuronide or sulfate compounds to enhance analyte detection by increasing the parent drug concentration of those drugs that are primarily metabolized by glucuronidation or sulfation. Hydrolysis procedures can be performed by acid, base, or enzyme sources (β-glucuronidase). Preanalytical hydrolysis can improve the overall detection of most opioids and benzodiazepine drugs. However, the limitation of this procedure is that the process can be time-consuming and prolong the turnaround time to result. In addition, chemical hydrolysis has the potential to degrade opioid and benzodiazepine drugs, whereas incomplete hydrolysis and variable hydrolysis efficiencies can occur with an enzymatic approach. Preanalytical hydrolysis can improve the sensitivity of drug detection for drug classes such as opiates/opioids and benzodiazepines, which are highly metabolized by glucuronidation and sulfation and should be implemented in analytical procedures to convert conjugated metabolites into the free (unbound) form.

Delegation of medical activities in acute pain therapy

Acute pain management is an interprofessional and interdisciplinary task and requires agood and trustful cooperation between stakeholders. Despite provisions in Germany according to which medical treatment can only be rendered by aformally qualified physician ("Arztvorbehalt"), aphysician does not have to carry out every medical activity in person. Under certain conditions, some medical activities can be delegated to medical auxiliary personnel but they need to be (1)instructed, (2)supervised and (3)checked by the physician himself; however, medical history, diagnostic assessment and evaluation, indications, therapy planning (e.g. selection, dosage), therapeutic decisions (e. g. modification or termination of therapy) and obtaining informed consent cannot be delegated. With respect to drug therapy, monitoring of the therapy remains the personal responsibility of the physician, while the actual application of medication can be delegated. From alegal perspective, the current practice needs to be stressed about what is within the mandatory requirements and what is not when medical activities are delegated to non-medical staff. The use of standards of care improves treatment quality but like any medical treatment it must be based on the physician's individual assessment and indications for each patient and requires personal contact between physician and patient. Delegation on the ward and in acute pain therapy requires the authorization of the delegator to give instructions in the respective setting. The transfer of non-delegable duties to non-medical personnel is regarded as medical malpractice.

Prospective study on prevalence, intensity, type, and therapy of acute pain in a second-level urban emergency department.

AimPain represents the most frequent cause for patient admission to emergency departments (EDs). Oligoanalgesia is a common problem in this field. The aims of this study were to assess prevalence and intensity of pain in patients who visited a second-level urban ED and to evaluate the efficacy of pharmacological treatment administered subsequent to variations in pain intensity.MethodsA 4-week prospective observational study was carried out on 2,838 patients who visited a second-level urban ED. Pain intensity was evaluated using the Numeric Rating Scale at the moment of triage. The efficacy of prescribed analgesic therapy was evaluated at 30 and 60 minutes, and at discharge. Data concerning pain intensity were classified as absent, slight, mild, or severe. Pain was evaluated in relation to the prescribed therapy.ResultsPain prevalence was 70.7%. Traumatic events were the primary cause in most cases (40.44%), followed by pain linked to urologic problems (13.52%), abdominal pain (13.39%), and nontraumatic musculoskeletal pain (7.10%). Only 32.46% of patients were given pharmacological therapy. Of these, 76% reported severe pain, 19% moderate, and 5% slight, and 66% received nonsteroidal anti-inflammatory drugs or paracetamol, 4% opioids, and 30% other therapies. A difference of at least 2 points on the Numerical Rating Scale was observed in 84% of patients on reevaluation following initial analgesic therapy.ConclusionPain represents one of the primary reasons for visits to EDs. Although a notable reduction in pain intensity has been highlighted in patients who received painkillers, results show that inadequate treatment of pain in ED continues to be a problem.

Regional anesthesia - are the standards changing?

Regional anesthesia has undergone many changes over the years and the increasing use of ultrasound has certainly played an important role in this. Apart from individual case reports in the literature of very different blocking options, some new procedures seem to have become established and can be broadly applied. Among these are blockades, by which ultrasound-guided injection of local anesthetics is carried out in fascial or muscular layers rather than around target nerves (e.g. cervical plexus blocks and truncal blocks). In addition, the precision with which ultrasound can be used to identify nerve structures led to an increasingly better definition of targets exemplified for interscalene or femoral nerve blocks. The use of ultrasound also seems to be helpful in the performance of neuraxial blocks, particularly in obese patients or patients with adifficult anatomy. With the implementation 10 years ago of aregistry for safety in regional anesthesia and acute pain therapy by the German Society of Anesthesiology and Intensive Care Medicine (DGAI) and the Association of German Anesthesiologists (BDA), it has been possible to answer important safety questions and define protective measures (e.g. tunnelling, antibiotic prophylaxis and sedation). Moreover, this registry can be used as abenchmark to compare the quality of regional anesthesia in individual hospitals with all other participating centers.

Prevalence and Predictors of Patient Nonadherence to Pharmacological Acute Pain Therapy at Home After Day Surgery: A Prospective Cohort Study.

Good adherence to prescribed analgesics can be crucial to suppress or even prevent acute postoperative pain after day surgery. The aim of this study was to analyze prevalence and predictors of analgesic nonadherence after day surgery. Elective patients scheduled for day surgery were prospectively enrolled from November 2008 to April 2010. Outcome parameters were measured by using questionnaire packages at 2 time points: 1week preoperatively and 4days postoperatively. The primary outcome parameter was analgesic nonadherence. Adherence was defined according to the patient's response to the questionnaire item "analgesia use as prescribed": full adherence, "yes"; partial adherence, "yes, sometimes"; nonadherence, "no." Bivariate and multivariate logistic regression analyses were performed to identify predictors of analgesic nonadherence. A total of 1,248 patients were included. The prevalence rates of analgesic nonadherence and partial adherence were 21.6% and 20.0%, respectively, in the total study population but dropped to 9.4% and 19.8%, respectively, in patients with moderate to severe pain. Low postoperative pain intensity and short duration of surgery were the most important predictors of analgesic nonadherence. The most important preoperative predictors for analgesic nonadherence were low preoperative pain intensity, low preoperative expectations of pain, and low fear of short-term effects of surgery. Analgesic nonadherence and partial adherence are common after day surgery but decrease as average pain intensity increases. Patients at risk for analgesic nonadherence can be identified during the preoperative period based on preoperative pain intensity, preoperative expectations of pain, and fear of surgery.

Effect on healthcare utilization and costs of spinal manual therapy for acute low back pain in routine care: A propensity score matched cohort study.

Spinal manual therapy (SMT) is a popular treatment option for low back pain (LBP). The aim of our analysis was to evaluate the effects of manual therapy delivered by general practitioners and ambulatory orthopedic surgeons in routine care on follow up consultations, sick leave, health service utilization and costs for acute LBP compared to matched patients not receiving manual therapy. This is a propensity score matched cohort study based on health claims data. We identified a total of 113.652 adult patients with acute LBP and no coded red flags of whom 21.021 (18%) received SMT by physicians. In the final analysis 17.965 patients in each group could be matched. Balance on patients’ coded characteristics, comorbidity and prior health service utilization was achieved. The provision of SMT for acute LBP had no relevant impact on follow up visits and days of sick leave for LBP in the index billing period and the following year. SMT was associated with a higher proportion of imaging studies for LBP (30.6% vs. 23%, SMD: 0.164 [95% CI 0.143–0.185]). SMT did not lead to meaningful savings by replacing other health services for LBP. SMT for acute non-specific LBP in routine care was not clinically meaningful effective to reduce sick leave and reconsultation rates compared to no SMT and did not lead to meaningful savings by replacing other health services from the perspective of health insurance. This does not imply that SMT is ineffective but might reflect a problem with selection of suitable patients and the quality and quantity of SMT in routine care. National Manual Medicine societies should state clearly that imaging is not routinely needed prior to SMT in patients with low suspicion of presence of red flags and monitor the quality of provided services.

Acute Pain Therapy in Appendectomy

The acute pain therapy in the setting of conventional or laparoscopic appendectomy has to be initiated by the surgeon. The success of acute pain therapy holds a direct relevance for quality of life, morbidity, chronification of pain, and economic aspects. A written consent between participating occupational groups and medical faculties based on existing guidelines is a crucial prerequisite for a well-functioning acute pain therapy. An adequately informed patient is able to actively take part in the process of his acute pain therapy. He becomes "part of the team". An efficient acute pain therapy always consists of a combination of non-medical procedures, technical operative aspects, and medical procedures.

Characteristics of Initial Prescription Episodes and Likelihood of Long-Term Opioid Use - United States, 2006-2015.

Because long-term opioid use often begins with treatment of acute pain (1), in March 2016, the CDC Guideline for Prescribing Opioids for Chronic Pain included recommendations for the duration of opioid therapy for acute pain and the type of opioid to select when therapy is initiated (2). However, data quantifying the transition from acute to chronic opioid use are lacking. Patient records from the IMS Lifelink+ database were analyzed to characterize the first episode of opioid use among commercially insured, opioid-naïve, cancer-free adults and quantify the increase in probability of long-term use of opioids with each additional day supplied, day of therapy, or incremental increase in cumulative dose. The largest increments in probability of continued use were observed after the fifth and thirty-first days on therapy; the second prescription; 700 morphine milligram equivalents cumulative dose; and first prescriptions with 10- and 30-day supplies. By providing quantitative evidence on risk for long-term use based on initial prescribing characteristics, these findings might inform opioid prescribing practices.

Cost-Effectiveness of Primary Care Management With or Without Early Physical Therapy for Acute Low Back Pain: Economic Evaluation of a Randomized Clinical Trial.

Economic evaluation of a randomized clinical trial. Compare costs and cost-effectiveness of usual primary care management for patients with acute low back pain (LBP) with or without the addition of early physical therapy. Low back pain is among the most common and costly conditions encountered in primary care. Early physical therapy after a new primary care consultation for acute LBP results in small clinical improvement but cost-effectiveness of a strategy of early physical therapy is unknown. Economic evaluation was conducted alongside a randomized clinical trial of patients with acute, nonspecific LBP consulting a primary care provider. All patients received usual primary care management and education, and were randomly assigned to receive four sessions of physical therapy or usual care of delaying referral consideration to permit spontaneous recovery. Data were collected in a randomized trial involving 220 participants age 18 to 60 with LBP <16 days duration without red flags or signs of nerve root compression. The EuroQoL EQ-5D health states were collected at baseline and after 1-year and used to compute the quality adjusted life year (QALY) gained. Direct (health care utilization) and indirect (work absence or reduced productivity) costs related to LBP were collected monthly and valued using standard costs. The incremental cost-effectiveness ratio was computed as incremental total costs divided by incremental QALYs. Early physical therapy resulted in higher total 1-year costs (mean difference in adjusted total costs = $580, 95% CI: $175, $984, P = 0.005) and better quality of life (mean difference in QALYs = 0.02, 95% CI: 0.005, 0.35, P = 0.008) after 1-year. The incremental cost-effectiveness ratio was $32,058 (95% CI: $10,629, $151,161) per QALY. Our results support early physical therapy as cost-effective relative to usual primary care after 1 year for patients with acute, nonspecific LBP. 2.

Association of Single-Nucleotide Polymorhism C3435T in the ABCB1 Gene with Opioid Sensitivity in Treatment of Postoperative Pain.

The minimal effective analgesic concentration of opioids required for satisfactory analgesia may differ significantly among the patients. Genetic factors may contribute to the variable response to opioids by affecting their pharmacokinetics or pharmacodynamics. Ninety nine patients undergoing abdominal surgery with colorectal anastomosis because of colorectal carcinoma were enrolled in the present study. C34535T was genotyped in all subjects and the patients were divided into three groups according to their genotype: CC-wild type homozygous, CT-mutant heterozygous and TT-mutant homozygous. Intravenous fentanyl, patient controlled analgesia was provided postoperatively for pain control in the first 24 hour after surgery. Opioid consumption, pain scores and the adverse side effects were evaluated. Our main result is that the patients in the CC genotype group consumed significantly more fentanyl (375.0 μg ± 43.1) than the patients in the TT group (295.0 μg ± 49.1) and the CT (356.4 μg ± 41.8) group in the treatment of postoperative pain. The patients in the TT group had lower VAS scores at 6h, 12h, 18 h and 24h postoperatively. There were no significant differences in the side effects among the three groups regarding the vomiting and the sedation score. The patients in the TT group had more frequently nausea score 1, than the patients in the other two groups. Our study indicates that the C3435T SNPs of the ABCB1 gene is associated with differences in the opioid sensitivity. The ABCB1 polymorphism may serve as an important genetic predictor to guide the acute pain therapy in postoperative patients.

CDC recommends limiting duration of opioid therapy for acute pain

CDC recommends limiting duration of opioid therapy for acute pain

SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL PROPERTIES OF NEW CODEINE FE(III) COMPLEX

ABSTRACT The reaction of FeCl 3 hexahydrate with C 18 H 20 NO 3 .PO 4 in acetonitrile produced new complex with general formula [Fe(L)]Cl 2 , (L= codeine). Characterization of the ligand and its complex were made by elemental analysis, FT-IR, 1 H-NMR, Raman and UV–visible spectroscopy. This new complex showed antitumor activity against two kinds of cancer cell lines: AGS (Stomach) and MCF-7 (Breast). Cell cytotoxic effects of the ligand and its complex were assayed by MTT and Natural-red tests. The antibacterial activity of ligand and complex against Pseudomonas aeruginosa , Staphylococcus aureus , Streptococcus pyogenes and Escherichia coli were also examined. Keywords: Codeine; Fe(III) complex; Synthesis; Anti-tumor; AGS and MCF-7; Antibacterial. e-mail: mojdeh.golzani@gmail.com INTRODUCTION Natural products play an important role in diseases control and treatment. The plants extracts are used in the treatment of human diseases all the time. From the last century, a scientific interest for phototherapy increased in several medical fields such as immunology, hematology and oncology [1-5].Currently there are three major ways of treating cancer: radiation therapy, surgery and cytotoxic drugs. Application of plants in medicine has affected the identification of natural compounds such as cocaine, morphine, vinblastine, tax land codeine [5-8].Many different coordination compounds and the mechanism of cytotoxic action have been discussed with regard to the development of new antitumor agents [8-15]. Numerous medicinal plants have been screened extensively for their antimicrobial potential worldwide [1, 11]. Morphine and its derivatives have received considerable attention as narcotic and used in lenitive drudge products. Morphine plays an important role in the therapy of acute and chronic pain. Exogenously delivered morphine acts in the body by activating different subtypes of opioid receptors [14].Over the last decades, proposals have accumulated that morphine present in mammalian tissues and fluids comes not only from an exogenous or dietary origin, but may also be biosynthesized de novo. Latest studies have unequivocally proven the existence of a mammalian morphine biosynthetic pathway [15], which consists of at least 19 steps and is different in its primary steps from that occurring in plants [16]. Meanwhile the endogenous morphine biosynthesis takes place in mammals, their cells and tissues are constantly exposed to certain amounts of morphine and its precursors [17].Investigation of lithium effect in opioid receptors on inhibitory avoidance response in mice has been reported. The results suggest that the opioid receptors in the central nervous system may be involved in the retrieval of lithium state dependent learning [18]. The lithium efficacy in controlling behaviors related with dopamine stimulants and manic states has been proposed [19]. Thus, it may be suggested that lithium‘s action may be mediated through dopamine receptors [20].Furthermore interactions between lithium and opioids have been reported. There is evidence that lithium is able to affect some actions of morphine. In particular, it has been shown that lithium inhibits morphine withdrawal signs in morphine-dependent mice [21], reduces the self-stimulation facilitated by morphine and the expression of tolerance to morphine [22] and alters the morphine induced analgesia in mice [23]. Both drugs produce a conditioned taste avoidance response and suppress schedule-induced polydipsia [24]. Another morphine precursor codeine, which stands in the biosynthetic pathway after salutaridinol, had a higher partial agonist efficacy. Their metal chelates are of interest due to their fascinating chemistry as well as antimicrobial and anti-cancer activities. The other natural ligand from plants such as phenolic compound of mono and sesquiterpenoid, flavonoids also can be used in synthesis of metal complex [25].Codeine is generally named codeine phosphate (Cod.P), morphine-3-methyl ether phosphate, methyl-morphine phosphate, or morphine monomethyl ether phosphate. It takes the general formulae of C

Effect of solubility enhancement on nasal absorption of meloxicam

Besides the opioids the standard management of the World Health Organization suggests NSAIDs (non-steroidal anti-inflammatory drugs) alone or in combination to enhance analgesia in malignant and non-malignant pain therapy. The applicability of NSAIDs in a nasal formulation is a new approach in pharmaceutical technology.In order to enhance the nasal absorption of meloxicam (MX) as an NSAID, its salt form, meloxicam potassium monohydrate (MXP), registered by Egis Plc., was investigated in comparison with MX. The physico-chemical properties of the drugs (structural analysis, solubility and dissolution rate) and the mucoadhesivity of nasal formulations were controlled. In vitro and in vivo studies were carried out to determine the nasal applicability of MXP as a drug candidate in pain therapy.It can be concluded that MX and MXP demonstrated the same equilibrium solubility at the pH5.60 of the nasal mucosa (0.017mg/ml); nonetheless, MXP indicated faster dissolution and a higher permeability through the synthetic membrane. The animal studies justified the short Tmax value (15min) and the high AUC of MXP, which is important in acute pain therapy. It can be assumed that the low mucoadhesivity of MXP spray did not increase the residence time in the nasal cavity, and the elimination from the nasal mucosa was therefore faster than in the case of MX. Further experiments are necessary to prove the therapeutic relevance of this MXP-containing innovative intranasal formulation.

Efficacy of intradiscal ozone gas therapy combined with physical therapy in contained lumber disc prolapse

Percutaneous intra-discal ozone therapy has promising results in contained lumber disc prolapse but the effectiveness of this treatment has been tested in large clinical studies show a positive outcome in 70%–80% of patients. To increase success rate of ozone discectomy and prevention of disc surgery, intradiscal ozone therapy combined with physical therapy may bring new options for the management of low back pain (LBP) due to lumber disc prolpase. This prospective experimental study was done from August 2014 to Octber 2014 at the Popular Medical College Hospital, Dhanmondi, Dhaka, Bangladesh with the intention to assess the efficacy of percutaneous intra-discal ozone therapy combined with physical therapy in acute and chronic low back pain due to contained prolapsed intervertebral lumber disc (PLID). Seven (7) ml of oxygen-ozone mixture at a concentration of 30 mc/ml was injected in the disc by ozone resistant syringe over a period of 15-20 seconds. All patients got physiotherapy for 30 minutes, two times/day, up to two weeks and strictly maintained activities of daily living (ADL). The main outcome variable was VAS(Visual Analogue Scale) &amp; ODI (Oswestry Disability Index). 100% patient experienced radiation of pain in the leg before ozone gas &amp; physical therapy and 90% had relieved radiation till 4th week. The reduction of VAS score from baseline to four weeks following treatment was 8.0±1.63 to 0.30±0.95. Reduction of Oswestry Disability Index (ODI) from baseline to four weeks following treatment was 37.7±6.5 to 15.8±1.0. Percutaneous intra-discal ozone therapy in combination with physical therapy is an effective treatment for management of low back pain (LBP) due to contained lumber disc prolpase.Bangladesh Med J. 2015 Sep; 44 (3): 146-151

Use of Scrambler Therapy in Acute Paediatric Pain: A Case Report and Review of the Literature.

We report our clinical experience on the effect of Scrambler Therapy (ST) for a child with acute mixed pain refractory to pharmacological treatment. ST, recently proposed as an alternative treatment for chronic neuropathic pain in adults, is a noninvasive approach to relieve pain, by changing pain perception at brain level. It is safe and has no side effects. Further research is needed to assess its efficacy for acute pain and for paediatric population.

Postoperative nausea and vomiting and opioids in children

Background We developed and implemented an interdisciplinary pain concept to assess and prevent pain as well as therapyrelated side effects with the objective of outcome improvement. Each pain management starts with profound preoperative information concerning the expected postoperative pain and what can be done to prevent it. For acute pain therapy a regular basic medication with non-opioids and an analgesic on demand (usually opioids) for the management of breakthrough pain of ≥ 4 is provided postoperatively [1]. There are several studies and risk scores concerning postoperative nausea and vomiting (PONV) related to opioid-treatment in adults [2-6]. We performed a study about this topic in children.

Acute inpatient multimodal pain therapy and rehabilitation

Acute inpatient multimodal pain therapy and rehabilitation

Trigger Point Therapy for Acute Back Pain

Trigger Point Therapy for Acute Back Pain

The Chiropractic Hospital-Based Interventions Research Outcomes Study: Consistency of Outcomes Between Doctors of Chiropractic Treating Patients With Acute Lower Back Pain

ObjectiveThe aim of this study was to determine if effectiveness differs between community-based doctors of chiropractic administering standardized evidence-based care that includes high-velocity low-amplitude spinal manipulative therapy (SMT) for acute low back pain (LBP). MethodsA secondary analysis of randomized controlled trial and observational pilot study data was performed with nonrandom allocation to 4 DCs. Patients included those with Quebec Task Force categories less than or equal to 2 and acute LBP of 2 to 4 weeks' duration. The intervention provided was clinical practice guidelines–based care including high-velocity low-amplitude SMT. Primary outcomes included changes from baseline in modified Roland Disability Questionnaire (RDQ) at 24 weeks. Comparisons of simple main effects at 24 weeks and of marginal main effects in repeated-measures analyses were performed. ResultsBetween groups, adjusted point-specific differences in RDQ change were minimally clinically important but not statistically significant at 24 weeks (largest pairwise difference, −3.1; 95% confidence interval, −6.3 to 0.1; overall P = .10). However, in optimal analyses that considered the repeated nature of the measurements for each outcome, significant differences in marginal mean RDQ changes were found between groups (largest pairwise difference, −3.8; 95% confidence interval, −4.9 to 2.6; overall P = .03). ConclusionsOverall, DCs differed modestly in their effectiveness in improving LBP-specific disability. The point estimates mirrored typically reported effect sizes from recent systematic reviews of SMT; however, confidence limits did not exclude clinically negligible effects.