Pain-relieving Drugs Research Articles

The Use of Analgesic and Other Pain-Relief Drugs to Manage Chronic Low Back Pain: Results from a National Survey.

To analyze and characterize the intake profile of pain-relief drugs in a population-based study of adults with chronic low back pain (CLBP). EpiReumaPt was a cross-sectional Portuguese population-based study (10,661 subjects). Self-reported active CLBP was considered to be low back pain on the day of enrollment and for ≥ 90 days. Prevalence and profile of analgesic intake was characterized among those self-reporting active CLBP, taking into account the intensity of pain and the World Health Organization (WHO) analgesic ladder. We further investigated whether the presence of active CLBP was a factor independently associated with the intake of analgesics (adjusted for potential confounders). Among 1,487 subjects with active CLBP, only 18.7% were using analgesic/pain-relief drugs. Estimated prevalence was anxiolytics, 14.1%; nonsteroidal anti-inflammatory drugs (NSAIDs), 12.3%; antidepressants, 10.1%; analgesic, antipyretics, 6.6%; anticonvulsants, 3.4%; central muscle relaxants, 2.6%; and analgesic opioids, 1.6%. Most subjects with severe pain were in the first step of the WHO analgesic ladder: NSAIDs plus anxiolytics (4.6%), NSAIDs plus antidepressants (3.2%), or NSAIDs plus muscle relaxants (2.5%). The presence of active CLBP was significantly associated with the intake of all therapeutic groups: antidepressants (odds ratio [OR] = 12.56; P < 0.001); centrally acting muscle relaxants (OR = 12.01; P < 0.001); anticonvulsants (OR = 9.27; P < 0.001); anxiolytics, sedatives, and hypnotics (OR = 8.86; P < 0.001); NSAIDs (OR = 8.56; P < 0.001); and analgesic opioids (OR = 8.13; P < 0.001). Analgesic/pain-relief drug intake in patients with active CLBP was very low, even for those with severe pain. The WHO analgesic ladder was carefully followed, with an extremely conservative use of analgesic opioids even for those with severe pain.

Overlapping Mechanisms of Stress-Induced Relapse to Opioid Use Disorder and Chronic Pain: Clinical Implications.

Over the past two decades, a steeply growing number of persons with chronic non-cancer pain have been using opioid analgesics chronically to treat it, accompanied by a markedly increased prevalence of individuals with opioid-related misuse, opioid use disorders, emergency department visits, hospitalizations, admissions to drug treatment programs, and drug overdose deaths. This opioid misuse and overdose epidemic calls for well-designed randomized-controlled clinical trials into more skillful and appropriate pain management and for developing effective analgesics that have lower abuse liability and are protective against stress induced by chronic non-cancer pain. However, incomplete knowledge regarding effective approaches to treat various types of pain has been worsened by an under-appreciation of overlapping neurobiological mechanisms of stress, stress-induced relapse to opioid use, and chronic non-cancer pain in patients presenting for care for these conditions. This insufficient knowledge base has unfortunately encouraged common prescription of conveniently available opioid pain-relieving drugs with abuse liability, as opposed to treating underlying problems using team-based multidisciplinary, patient-centered, collaborative-care approaches for addressing pain and co-occurring stress and risk for opioid use disorder. This paper reviews recent neurobiological findings regarding overlapping mechanisms of stress-induced relapse to opioid misuse and chronic non-cancer pain, and then discusses these in the context of key outstanding evidence gaps and clinical-treatment research directions that may be pursued to fill these gaps. Such research directions, if conducted through well-designed randomized-controlled trials, may substantively inform clinical practice in general medical settings on how to effectively care for patients presenting with pain-related distress and these common co-occurring conditions.

κ-Opioid receptor participates of NSAIDs peripheral antinociception

NSAIDs represent some of the most widely prescribed drugs for relief of short-term fever, pain and inflammation. The participation of the opioid system in the peripheral is poorly understood. The aim of this study was evaluate the role of opioid system in the peripheral antinociception by diclofenac and dipyrone. To test this hypothesis, opioid receptor antagonists were evaluated using the rat paw pressure test, in which pain sensitivity is increased by intraplantar injection of prostaglandin E2 (PGE2, 2μg). Diclofenac (20μg/paw) and Dipyrone (40μg/paw) administered locally into the right paw elicited an antinociceptive effect. It was used naloxone (50μg/paw), a non-selective opioid receptor antagonist, which antagonized peripheral antinociception induced by diclofenac and dipyrone. Selectively, it was evaluated the μ-, δ- and κ-opioid receptor antagonists, respectively, clocinnamox (40μg/paw), naltrindole (50μg/paw) and nor-binaltorphimine (20, 40 and 80μg/paw). Our data indicated that only the κ-opioid antagonist was capable to reverse the peripheral antinociception by NSAIDs. The present results provide evidence that the opioid system participated in the diclofenac and dipyrone-induced peripheral antinociception by indirect activation of κ-opioid receptor probable by release of endogenous opioids such as dynorphins.

Systematic review: Is Metoclopramide more effective than Sumatriptan in relieving pain from migraine in adults in the Emergency Department (ED) setting?

Migraine headache is a common disorder; patients attending Emergency Departments (ED) for migraine symptoms internationally account for 1–3% of total ED annual attendances.A systematic review was undertaken of reports comparing the effectiveness of metoclopramide intravenously (IV) with that of sumatriptan subcutaneously (SC), in an ED setting, for the immediate relief of migraine and their measurable effects in relieving pain intensity.Findings of two identified comparable reports confirm the individual efficacy of the study drugs in pain relief. However, whilst one report concludes that there is no statistical or significant clinical advantage for one drug over the other, the other report suggests that metoclopramide has a distinct advantage.One study is well structured methodologically, but the other has significant risk of bias.The analysis of the chosen studies demonstrates the need for rigorous study design and robust reporting requirements to obviate this risk. Further studies are required to explore comparable effect.Implications for clinical practice from the report outcomes indicate the individual effectiveness of both study drugs in providing pain relief for migraine in the Emergency setting, but not the comparable efficacy of one drug over the other.

Evidence of Core-Shell Formation between NdFeO3 Nano-Perovskite and Ionic Liquid Crystal and Its Application in Electrochemical Sensing of Metoclopramide

A simple and sensitive electrochemical method for determination of metoclopramide was developed based on the in-situ modification of carbon paste electrode (CpE) with NdFeO3 (NF) nano-perovskite and 2-chloro-1,3-dimethyl-imidazolinium hexafluorophosphate ionic liquid crystal (ILC) in presence of sodium dodecyl sulfate (SDS); NFILCMCpE…SDS. A core-shell formation between NdFeO3 and ILC was confirmed affecting the catalytic activity of the nanocomposite. XRD, FTIR, TEM, BET, SEM and EDAX were used to elucidate the orthorhombic structure of NdFeO3 and give a complete characterization of the proposed composite sensor. Cyclic voltammetry and electrochemical impedance spectroscopy measurements revealed enhanced electrochemical activity for metoclopramide at the proposed sensor surface. The components of the composite sensor exhibit synergistic role in enhancing the sensor signal toward the drug. A linear calibration curve for metoclopramide was obtained at the proposed sensor in the concentration range of 0.4 μmol L−1 to 300 μmol L−1 with detection limit of 1.91 nmol L−1 and sensitivity of 203.56 μA/mmol L−1. NFILCMCpE…SDS was successfully applied for the sensitive determination of metoclopramide in its commercial tablets and real samples; urine and blood serum. Also, the proposed sensor exhibited anti-interference properties toward metoclopramide determination in presence of common interferents, pain relief drugs or neurotransmitters. The proposed sensor was very stable toward the electrochemical response of metoclopramide up to one month of storage.

INVESTIGATION OF THE EFFECTIVENESS OF ACUPUNCTURE IN THE TREATMENT OF FROZEN SHOULDER.

Background:Adhesive capsulitis is a common disease that causes pain and reduced range of motion, but vague on the shoulder. Woman are affected fewer than men, but there is no known racial or genetic tendency. Most patients with adhesive capsulitis will improve with nonsurgical treatment. Acetaminophen and nonsteroidal anti-inflammatory drugs for pain relief in patients without contraindication are first-line options. Acupuncture considered being safe and effective in reducing pain. The aim of this study was to Investigation of the effectiveness of acupuncture in the treatment of frozen shoulder.Materials and Methods:In a controlled clinical trial, patients referred to the Baqiatallah clinic in 91 years with shoulder pain, frozen shoulder diagnosed based on history and physical exam, they have been enrolled. Indicators measured in the study was included the involved joint pain, range of motion and quality of life. Patients, first at baseline, one and a half months later (end of session) and then 3 months after the examination information about each individual entered in the from of questionnaires were pre-determined and data were analyzed by SPSS 17 software.Results:In this clinical trial study total 40 patients with frozen shoulder (20 interference with the acupuncture and 20 people control) study that patients average age 55/54. Age maximum 71 years and minimum 44 years. Acupuncture in the treatment of frozen shoulder with the results achieved in the general case acupuncture may improve shoulder motion in patients. VAS index at three months after treatment compared with the control group had a greater improvement.Conclusion:In the case of acupuncture and ultimately improve the overall look of all the movement of flexion and adduction of the shoulder, but the movement has been further improved, VAS index at three months after treatment compared with the control group had a greater improvement and finally, we perform acupuncture as a way to improve shoulder motion in patients with frozen shoulder offered.

Rectal indomethacin use in pain relief during hysterosalpingography: A randomized placebo controlled trial.

To evaluate the effectiveness of a rectal nonsteroidal anti-inflammatory drug (indomethacin) for pain relief during a hysterosalpingography (HSG). This prospective, randomized study included 82 women divided randomly into two groups. The study group received self-administered rectal indomethacin, while the control group received a placebo before the procedure. Degrees of pain were evaluated using the visual analog scale (VAS) at four different steps during the procedure and 30 min afterwards. The anxiety-depression status of the patients was evaluated using a validated Turkish version of the Beck anxiety-depression form before the procedure. There were no statistically significant differences in the demographic characteristics of patients. The mean pain scores during tenaculum application (step 2), cervical traction (step 3), contrast injection (step 4) and 30 min after the procedure, were significantly lower in the study than the control group (P < 0.05). Step 4 was the most painful in both groups (VAS scores 3.2 ± 0.6 study vs. 5.3 ± 1.1 control). The mean pain score in step 4 for patients with abnormal HSG results was significantly higher than in patients with normal HSG results (P < 0.05). The mean anxiety and depression scores immediately before the procedure were not statistically different between the groups (P = 0.610 and P = 0.129, respectively). Our study demonstrated a significant reduction in pain in patients who received a single rectal dose of indomethacin; therefore, we recommend the use of rectal indomethacin for reducing pain during a HSG procedure.

Resonance Energy Transfer Relates the Gas-Phase Structure and Pharmacological Activity of Opioid Peptides.

Enkephalins are efficient pain-relief drugs that bind to transmembrane opioid receptors. One key structural parameter that governs the pharmacological activity of these opioid peptides and is typically determined from condensed-phase structures is the distance between the aromatic rings of their Tyr and Phe residues. We use resonance energy transfer, detected by a combination of cold ion spectroscopy and mass spectrometry, to estimate the Tyr-Phe spacing for enkephalins in the gas phase. In contrast to the condensed-phase structures, these distances appear to differ substantially in enkephalins with different pharmacological efficiencies, suggesting that gas-phase structures might be a better pharmacophoric metric for ligand peptides.

Resonance Energy Transfer Relates the Gas‐Phase Structure and Pharmacological Activity of Opioid Peptides

AbstractEnkephalins are efficient pain‐relief drugs that bind to transmembrane opioid receptors. One key structural parameter that governs the pharmacological activity of these opioid peptides and is typically determined from condensed‐phase structures is the distance between the aromatic rings of their Tyr and Phe residues. We use resonance energy transfer, detected by a combination of cold ion spectroscopy and mass spectrometry, to estimate the Tyr–Phe spacing for enkephalins in the gas phase. In contrast to the condensed‐phase structures, these distances appear to differ substantially in enkephalins with different pharmacological efficiencies, suggesting that gas‐phase structures might be a better pharmacophoric metric for ligand peptides.

Lidocaine Skin Patch (Lidopat® 5%) Is Effective in the Treatment of Traumatic Rib Fractures: A Prospective Double-Blinded and Vehicle-Controlled Study

Objective: The purpose of this study was to determine the efficacy of the Lidopat® 5% skin patch in relieving rib fracture pain. Subjects and Methods: From June 2009 to May 2011, 44 trauma patients with isolated rib fractures were enrolled in this study and randomized in a double-blind method into 2 groups. The experimental group (group E: 27 patients) used a Lidopat® 5% skin patch at the trauma site and took an oral analgesic drug for pain relief. The placebo group (group P: 17 patients) used a placebo vehicle patch and an oral analgesic drug. Results: The mean age, weight and hospital stay of patients were 56.8 ± 13.8 years, 67.4 ± 12.6 kg and 6.34 ± 1.3 days, respectively. In the first 4 days, there were no significant differences in pain scores between the groups (p > 0.05). After the 5th day, the average pain score was significantly less in group E (mean 1.5) than in group P (mean 3.10; p < 0.05). There was no significant difference in the number of fractured ribs between groups (p = 0.904). The use of meperidine and the length of hospital stay (6.0 vs. 6.9 days) were both significantly less in group E (p = 0.043 and 0.009, respectively). Conclusion: In this study, the use of the Lidopat® 5% skin patch in patients with isolated rib fractures alleviated pain and shortened the hospital stay, and a lower dose of pain-relieving medication was used.

Prolonged Suppression of Neuropathic Pain by Sequential Delivery of Lidocaine and Thalidomide Drugs Using PEGylated Graphene Oxide

The management of patients with neuropathic pain is challenging. Monotherapy with a single pain relief drug may encounter different difficulties, such as short duration of efficacy and hence too many times of drug administration, and inadequate drug delivery. Recently, nanocarrier-based drug delivery systems have been proved to provide promising strategies for efficient drug loading, delivery, and release. In the present study, we developed poly(ethylene glycol) methyl ether functionalized graphene oxide (GO) bearing two commonly used drugs of lidocaine (LDC) and thalidomide (THD) as an agent for the treatment of neuropathic pain. The sequential drug release of LDC and THD from the developed LDC-THD-GO nanosheets exhibited a synergistic effect on neuropathic pain in vitro and in vivo, as evidenced by the increased pain threshold in mechanical allodynia and hyperalgesic response tests, and the improved inhibition of proinflammatory cytokines TNF-α, IL-1β, IL-6, and nitric oxide. We believed that the present study herein would hold promise for future development of a new generation of potent agents for neuropathic pain relief.

Electrospun nanofibrous CMC/PEO as a part of an effective pain-relieving wound dressing

A novel two-layered pain-relieving wound dressing was prepared from a combination of biocompatible polymers: carboxymethylcellulose and polyethyleneoxide, and two types of pain-relieving drugs: the non-steroid anti-inflammatory diclofenac and the local anesthetic lidocaine. To achieve the two-layered structure, electrospinning and impregnation of a commercially available wound dressing Aquacel® were used for preparation of respective layers. The electrospun nanofibers have been shown to possess similar features as found in the extracellular matrix, an important component of the skin. This characteristic could significantly contribute to the efficiency of wound healing. The second layer is based on Aquacel®, an important wound dressing in modern wound care. Since pain can drastically lower the wound healing process, as well as it is known to decrease the overall quality of patient life, pain-relieving drugs are very interesting for wound care applications. For efficient pain reduction, two types of drugs were used. When combined, these can cover different types of wound-related pain (due to the cause and treatment) and hence additionally aid the wound healing process. The combined features of the incorporated pain-relieving drugs and the mentioned materials are therefore very interesting for future studies toward clinical testing of possible prototype products.

INVESTIGAÇÃO DA SUSPEITA DE DESVIO DE QUALIDADE EM UMA SOLUÇÃO INJETÁVEL DE CITRATO DE FENTANILA

&lt;p&gt;A fentanila é um fármaco analgésico de uso hospitalar principalmente indicado como componente da anestesia. Devido a uma queixa técnica de um hospital de São Paulo apontando a ineficácia terapêutica de uma solução injetável de citrato de fentanila após o uso na anestesia, amostras do produto foram colhidas pela vigilância sanitária para análise. O objetivo deste trabalho foi realizar ensaios físico-químicos nas amostras, com prioridade para identificação e teor do fármaco, utilizando-se um cromatógrafo líquido de alta eficiência equipado com detector de arranjo de diodos. Os dois lotes analisados apresentaram identificação positiva para citrato de fentanila e 97,30% do teor declarado do fármaco; resultados satisfatórios em relação ao especificado pelo fabricante do produto. Assim, foi possível excluir desvios no teor do fármaco como a causa da ineficácia terapêutica, indicando a necessidade de investigações complementares e levantando maiores discussões sobre o caso.&lt;/p&gt;

Structure activity studies of an analgesic drug tapentadol hydrochloride by spectroscopic and quantum chemical methods

Tapentadol is a novel opioid pain reliever drug with a dual mechanism of action, having potency between morphine and tramadol. Quantum chemical calculations have been carried out for tapentadol hydrochloride (TAP.Cl) to determine the properties. The geometry is optimised and the structural properties of the compound were determined from the optimised geometry by B3LYP method using 6–311++G(d,p), 6–31G(d,p) and cc–pVDZ basis sets. FT-IR and FT–Raman spectra are recorded in the solid phase in the region of 4000–400 and 4000–100 cm−1, respectively. Frontier molecular orbital energies, LUMO–HOMO energy gap, ionisation potential, electron affinity, electronegativity, hardness and chemical potential are also calculated. The stability of the molecule arising from hyperconjugative interactions and charge delocalisation has been analysed using NBO analysis. The 1H and 13C nuclear magnetic resonance chemical shifts of the molecule are analysed.

Removal of pain-relieving drugs from aqueous solutions using Octolig and selected metalloligs

The possibility of removing certain pharmaceuticals (acetaminophen and naproxen) from water was tested using Octolig, a commercially available material with polyethylenediimine moieties covalently attached to high-surface area silica gel. In addition, the efficacy of two transition metals (cupric and ferric) derivatives of Octolig was tested. Previously amoxicillin had been successfully subjected to column chromatography for removal by means of ion encapsulation, the effectiveness of which would depend upon having appropriate anionic functional groups. Both pharmaceuticals were removed by passage over Octolig columns, though with less effectiveness than was achieved previously with xanthenylbenzenes or selected food dyes. Somewhat greater removal, ca 90%, was achieved using Cuprilig, the copper(II) derivative, but not with Ferrilig the iron(III) derivative, perhaps because the hydroxide counter ion was more closely associated with the transition metal ion and was not available to assist in proton removal.

Analgesic treatment of cancer pain

Cancer pain can be nociceptive, neuropathic or mixed. It is linked to the tumour, to the metastases and to the treatments for the disease and is managed by multimodal analgesia corresponding to the pain relief drugs of the WHO's pain ladder, antidepressants, antiepileptic drugs and local anaesthetics.

(338) Human sensory neurons: cellular excitability, sensitization, and ion channel conductances

Biological differences in sensory processing between human and model organisms may present significant obstacles to translational approaches in treating chronic pain. Such obstacles may include functional differences in target receptor pharmacology and signaling or fundamental differences in neuronal physiology. While cultures of rodent dorsal root ganglion (rDRG) neurons have proven useful for identifying new analgesic targets and elucidating signaling pathways, notable translational failures have recently raised questions about the wisdom of developing drugs for pain relief in rodents for eventual use in humans.

Inhibitory effects of pain relief drugs on neurological enzymes: Implications on their potential neurotoxicity to aquatic animals

Pain relief medications commonly occur in the aquatic environment at measurable levels. While the neurotoxicity of pain relievers to higher vertebrates is currently known, little is known about their effects on aquatic animals. This study investigated the neurotoxicity of pain relievers to aquatic animals. We used three neurological enzymes, cholinesterase (ChE), adenosine triphosphatase (ATPase), and monoamine oxidase (MAO), from a freshwater planarian (Dugesia japonica) and green neon shrimp (Neocaridina denticulata) as biomarkers to examine the effects of pain relievers on in vitro activity. The activity of MAO and ChE, but not ATPase, was significantly inhibited by acetaminophen, but not by other pain relievers examined. It was likely that the inhibitory effects of acetaminophen on shrimp neurological enzymes were more severe than on the planarian. These findings suggest that acetaminophen is potentially neurotoxic to aquatic animals, at least in terms of neurotransmission disturbance.

&lt;i&gt;In Vitro&lt;/i&gt; Controlled Release of Topically Applied Capsaicin from Silk Hydrogel: A Study Contributed to the Pain Relief System

The availability of a safety and efficient vehicle for pain relief system remains major challenge. The clinical applications of capsaicin are restricted by lacking a long-term drug delivery system The purpose of the present study is to control the release of topically applied capsaicin from silk fibroin hydrogel, all factors including proportions of silk fibroin, amount of capsaicin and penetration enhancer are studied. The capsaicin release behavior was measured by using x-ray fluorescence spectroscopy (XRF). X-ray diffraction (XRD) was used to investigate structure of the silk fibroin hydrogels. The results indicate that the silk can protect the capsaicin and also all factors involved influence the capsaicin release behavior. The release of the capsaicin may be controlled exactly by changing the factors involved. So the silk fibroin hydrogels make the capsaicin a promising pain relief drug used in clinic in the future.

Neck pain and headache as the only manifestation of cervical artery dissection

To analyze clinical and neuroimaging data in patients with neck pain and headache as the only manifestation of the internal carotid artery (ICA) dissection (ICAD) and vertebral artery (VA) dissection (VAD). One hundred and sixty-one patients (mean age - 37.4±4,99 years, 84 women, 52%) with cervical artery dissection (CAD) verified by magnetic resonance imaging (MRI) were enrolled. Neck pain and headache were the only CAD manifestation in 33 patients (mean age 37,3±7,4 yars, 28 women, 85%). The localization of the dissections in these patients was the following: one VA (15 patients), two VA (9), one ICA (7), two ICA (1), one ICA + two VA (1). The whole number of dissected arteries was 45: extracranial localization - 38, extra-intracranial - 6, intracranial - 1. Dissection led to stenosis of the arterial lumen in 41 arteries, to occlusion - in 2 and to dual lumen in 2 arteries. Small aneurism was found in 4 arteries. Combination of headache and the neck pain was observed in 26 out of 33 patients (79%), the only headache in 4 patients, the only neck pain in 3 patients. Along with this, 9 out of 24 VAD patients had the shoulder and/or arm pain. Headache in VAD patients was located more often in the occipital region (18 out of 24) that had never been observed in ICAD patients (p=0.0009). Fronto-temporal pain was observed more often in ICAD patients (5 out of 8 patients) than in VAD (2 out of 24 patients) (p=0.003). Neck pain in all VAD patients in comparison with 3 out ofI8 [CAD patients had posterior localization (p=0,007). Anterolateral neck pain was observed in 4 out ofI8 ICAD patients and in no patients with VAD (p=0.0009). The pain appearance was abrupt in all ICAD patients and most of the VAD patients. In 8 VAD patients the pain has been increasing during several hours. The pain intensity was severe in 19 patients, moderate in 12 and mild in 2. The characteristics of the pain were as following: constrictive/dull (26 patients), throbbing (1 patient) or combined (6 patients). Pain was increasing in a stepwise manner during the first days in 14 out of 24 VAD patients and in no one of ICAD patients (p=0.008). The mean pain duration period was 31 8 ± 15,7 days. Pain relief drugs were ineffective or had a short effect in 97% of patient. Isolated pain is more characteristic for women with VAD. Usually pain is presented as a combination of headache and neck pain. Pain localization, mode of appearance and the course are different in VAD and ICAD. The rarity of occlusion among patients with <<pain-only>> manifestation let to suggest that the intramural hematoma in this group of patients spreads to the adventitia that can reflect media weakness. Arterial wall changes underlying its weakness seem to be sex-hormone dependent taking into consideration the high predominace of women in cad manifested by isolated pain.