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International Journal of Molecular... Mar 2022One of the strategies in the search for safe and effective analgesic drugs is the design of multitarget analgesics. Such compounds are intended to have high affinity and... (Review)
Review
One of the strategies in the search for safe and effective analgesic drugs is the design of multitarget analgesics. Such compounds are intended to have high affinity and activity at more than one molecular target involved in pain modulation. In the present contribution we summarize the attempts in which fentanyl or its substructures were used as a μ-opioid receptor pharmacophoric fragment and a scaffold to which fragments related to non-opioid receptors were attached. The non-opioid 'second' targets included proteins as diverse as imidazoline I binding sites, CB cannabinoid receptor, NK tachykinin receptor, D dopamine receptor, cyclooxygenases, fatty acid amide hydrolase and monoacylglycerol lipase and σ receptor. Reviewing the individual attempts, we outline the chemistry, the obtained pharmacological properties and structure-activity relationships. Finally, we discuss the possible directions for future work.
Topics: Analgesics; Analgesics, Opioid; Fentanyl; Receptors, Drug; Receptors, Opioid, mu; Structure-Activity Relationship
PubMed: 35269909
DOI: 10.3390/ijms23052766 -
Pharmaceutical Biology Dec 2023Linn (Leguminosae) is often used in Yi ethnic medicine to treat pain, fracture, and rheumatism.
CONTEXT
Linn (Leguminosae) is often used in Yi ethnic medicine to treat pain, fracture, and rheumatism.
OBJECTIVE
To explore the therapeutic potential of doliroside B (DB) from and its disodium salt (DBDS) and the underlying mechanism in pain.
MATERIALS AND METHODS
In the writhing test, Kunming mice were orally treated with DB and DBDS at doses of 0.31, 0.62, 1.25, 2.5, and 5 mg/kg. Vehicle, morphine, indomethacin, and acetylsalicylic acid were used as negative and positive control on the nociception-induced models, respectively. In the hot plate test, mice were orally treated with DB and DBDS at doses of 2.5, 5, 10, and 20 mg/kg. In the formalin test, mice were orally treated with DB and DBDS at doses of 2.5, 5, 10, and 20 mg/kg. In the meanwhile, lipopolysaccharide-induced inflammatory model in RAW264.7 macrophages was adopted to study the mechanism of pain alleviation for DBDS.
RESULTS
DBDS (5 mg/kg) inhibited the writhing number by 80.2%, which exhibited the highest antinociceptive activity in pain models. DBDS could selectively inhibite the activity of COX-1. Meanwhile, it also reduced the production of NO, iNOS, and IL-6 by 55.8%, 69.0%, and 49.9% inhibition, respectively. It was found that DBDS also positively modulated the function of GABA receptor.
DISCUSSION AND CONCLUSIONS
DBDS displayed antinociceptive activity by acting on both the peripheral and central nervous systems, which may act on multitargets. Further work is warranted for developing DBDS into a potential drug for the treatment of pain.
Topics: Animals; Mice; Analgesics; Pain; Plant Extracts
PubMed: 36628487
DOI: 10.1080/13880209.2022.2163407 -
Journal of the American Academy of... Sep 2023The aging population and the obesity epidemic have led to an increased rate of joint arthroplasty procedures, specifically total knee arthroplasty and total hip... (Review)
Review
The aging population and the obesity epidemic have led to an increased rate of joint arthroplasty procedures, specifically total knee arthroplasty and total hip arthroplasty. These surgeries are associated with increased hospital length of stay and, consequently, higher costs. Despite the benefits of outpatient surgery, only a small percentage of total joint arthroplasties (TJAs) are done in this manner. We reviewed the most up-to-date trends for outpatient TJA and discussed essential factors for a successful outpatient program, including the proper patient selection process and best available anesthetic and analgesic options, along with their risks and benefits. Risk stratification tools, such as the Outpatient Arthroplasty Risk Assessment, are helpful for predicting outcomes regarding outpatient TJA, and neuraxial anesthesia should be considered to minimize complications and facilitate early discharge. A multimodal analgesia regimen could be effective for pain management in outpatient TJA, and the currently recommended peripheral nerve blocks for total hip arthroplasty and total knee arthroplasty are the fascia iliaca compartment block and adductor canal block, respectively. However, blocks should be carefully considered for outpatient procedures. Enhanced recovery after surgery (ERAS) protocols help to guide perioperative care teams and allow for improved patient recovery, decreased length of stay, and increased patient satisfaction.
Topics: Humans; Aged; Outpatients; Anesthesiology; Analgesics; Arthroplasty, Replacement, Knee; Anesthesia, Conduction
PubMed: 37669101
DOI: 10.5435/JAAOSGlobal-D-22-00259 -
Acta Orthopaedica Jan 2022Background and purpose - Total hip arthroplasty (THA) is an effective and common procedure. However, persistent pain and analgesic requirement up to 2 years after THA...
Background and purpose - Total hip arthroplasty (THA) is an effective and common procedure. However, persistent pain and analgesic requirement up to 2 years after THA surgery are common. We examined the trends in the utilization of analgesics before and after THA, overall, and in relation to socioeconomic status (SES) in a populationbased cohort. Patients and methods - We used the Danish Hip Arthroplasty Register to identify 103,209 patients who underwent THA between 1996 and 2018. Data on prescriptions and SES markers was obtained from Danish medical databases. Prevalence rates of redeemed prescriptions for analgesics with 95% confidence intervals were calculated for 4 quarters before and 4 quarters after THA for the entire THA population, and by 3 SES markers (education, cohabiting status, and wealth). Results - Overall, the prevalence of analgesic use prior to surgery was 42% at 9-12 months and 59% at 0-3 months before the THA. The prevalence of analgesics reached its highest at 64% 0-3 months after THA but declined to 27% at 9-12 months after THA. Low education, living alone, and having low wealth (low SES) were associated with higher prevalence of analgesics use both before and after THA. Interpretation - 59% of patients used analgesics 0-3 months before surgery, which could indicate that THA might not be considered the last option for treatment and that surgery criteria might depend more on factors such as patient preferences or hip function. Moreover, health professionals should prioritize the use of a detailed plan when phasing out analgesics after THA to counteract unnecessary use, especially when treating patients with low SES.
Topics: Analgesics; Arthroplasty, Replacement, Hip; Cohort Studies; Humans; Social Class
PubMed: 34981126
DOI: 10.2340/17453674.2021.955 -
Anaesthesia Feb 2013Eighteen published trials have examined the use of neuraxial magnesium as a peri-operative adjunctive analgesic since 2002, with encouraging results. However, concurrent... (Review)
Review
Eighteen published trials have examined the use of neuraxial magnesium as a peri-operative adjunctive analgesic since 2002, with encouraging results. However, concurrent animal studies have reported clinical and histological evidence of neurological complications with similar weight-adjusted doses. The objectives of this quantitative systematic review were to assess both the analgesic efficacy and the safety of neuraxial magnesium. Eighteen trials comparing magnesium with placebo were identified. The time to first analgesic request increased by 11.1% after intrathecal magnesium administration (mean difference: 39.6 min; 95% CI 16.3-63.0 min; p = 0.0009), and by 72.2% after epidural administration (mean difference: 109.5 min; 95% CI 19.6-199.3 min; p = 0.02) with doses of between 50 and 100 mg. Four trials monitored for neurological complications: of the 140 patients included, only a 4-day persistent headache was recorded. Despite promising peri-operative analgesic effect, the risk of neurological complications resulting from neuraxial magnesium has not yet been adequately defined.
Topics: Analgesics; Headache; Humans; Magnesium Sulfate; Pain, Postoperative; Postoperative Complications; Treatment Outcome
PubMed: 23121635
DOI: 10.1111/j.1365-2044.2012.07337.x -
Journal of Science and Medicine in Sport Oct 2022To identify the prevalence, frequency, adverse effects, and reasons for analgesic use in youth athletes. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To identify the prevalence, frequency, adverse effects, and reasons for analgesic use in youth athletes.
DESIGN
Systematic review and meta-analysis.
METHODS
Systematic searches in Embase, Medline, and SPORT-Discus from inception to September 2021, screening of reference lists, and citation tracking were performed to identify observational studies including athletes aged 15-24 years and reporting data on prevalence and/or frequency of analgesic use. Study quality was assessed using the Newcastle-Ottawa Scale. Random-effect proportion meta-analyses, stratified by type of analgesic medication and prevalence measure, estimated the prevalence of analgesic use. Data on usage frequency, adverse events, and reasons for analgesic use was synthesized narratively.
RESULTS
Forty-nine studies were included (44,381 athletes), of which 19 were good/high quality. Seven categories of analgesics were identified across 10 prevalence time-points. Meta-analyses suggested common use of NSAIDs (point prevalence 48 % [95 % CI 23 % to 73 %], in-season prevalence 92 % [95 % CI 88 % to 95 %]). The lowest prevalence was found for use of local anesthetic injections within the previous 12 months (2 % [95 % CI 1 % to 3 %]). Seven to 50 % of athletes reported weekly analgesics use. The proportion of adverse events ranged from 3.3 % to 19.2 %. Reasons for using analgesics included treatment of sports-related pain or injury, to treat illness, and to enhance performance.
CONCLUSIONS
Analgesics are commonly used in youth athletes, but estimates vary depending on type of analgesic and prevalence measure. As the majority of studies were of poor methodological quality, future high-quality research should include prospective data collection of analgesic use to understand consumption trajectories.
Topics: Adolescent; Analgesics; Anesthetics, Local; Anti-Inflammatory Agents, Non-Steroidal; Athletes; Humans; Prevalence
PubMed: 36100523
DOI: 10.1016/j.jsams.2022.08.018 -
Pharmacology Research & Perspectives Dec 2021Chemotherapy-induced peripheral neuropathy (CIPN) frequently occurs in cancer patients. This side effect lowers the quality of life of patients and may cause the... (Review)
Review
Chemotherapy-induced peripheral neuropathy (CIPN) frequently occurs in cancer patients. This side effect lowers the quality of life of patients and may cause the patients to abandon chemotherapy. Several medications (e.g., duloxetine and gabapentin) are recommended as remedies to treat CIPN; however, usage of these drugs is limited because of low efficacy or side effects such as dizziness, nausea, somnolence, and vomiting. From ancient East Asia, the decoction of medicinal herbal formulas or single herbs have been used to treat pain and could serve as alternative therapeutic option. Recently, the analgesic potency of medicinal plants and their phytochemicals on CIPN has been reported, and a majority of their effects have been shown to be mediated by glial modulation. In this review, we summarize the analgesic efficacy of medicinal plants and their phytochemicals, and discuss their possible mechanisms focusing on glial modulation in animal studies.
Topics: Analgesics; Animals; Antineoplastic Agents; Humans; Neoplasms; Neuralgia; Neuroglia; Phytochemicals; Plant Preparations; Plants, Medicinal; Quality of Life
PubMed: 34676990
DOI: 10.1002/prp2.819 -
Molecules (Basel, Switzerland) Jul 2023Neuropathic 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... (Review)
Review
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.
Topics: Humans; Analgesics, Opioid; Quality of Life; Neuralgia; Neuroglia; Analgesics; Receptors, Chemokine
PubMed: 37570736
DOI: 10.3390/molecules28155766 -
Molecules (Basel, Switzerland) Apr 2024Various plant species from the genus have been claimed to be beneficial for pain relief. The PRISMA approach was adopted to identify studies that reported analgesic... (Review)
Review
Various plant species from the genus have been claimed to be beneficial for pain relief. The PRISMA approach was adopted to identify studies that reported analgesic properties of plants from the genus. Out of 450 records returned, 19 primary studies revealed the analgesic potential of nine species including (1) , (2) , (3) , (4) , (5) , (6) , (7) , (8) and (9) . Six of the species, 1, 3, 4, 7, 8 and 9, demonstrated peripheral antinociceptive properties as they inhibited acetic-acid-induced writhing in animal models. Species 1, 3, 4, 8 and 9 further showed effects via the central analgesic route at the spinal level by increasing the latencies of heat stimulated-nocifensive responses in the tail flick assay. The hot plate assay also revealed the efficacies of 4 and 9 at the supraspinal level. Species 6 was reported to ameliorate hyperalgesia induced via partial sciatic nerve ligation (PSNL). The antinociceptive effects of 1 and 3 were attributed to the regulatory effects of their bioactive compounds on inflammatory mediators. As for 2 and 5, their analgesic effect may be a result of their activity with the 5-hydroxytryptamine 1A receptor (5-HTR) which disrupted the pain-stimulating actions of 5-HT. Antinociceptive activities were documented for various major compounds of the plants. Overall, the findings suggested species as good sources of antinociceptive compounds that can be further developed to complement or substitute prescription drugs for pain management.
Topics: Litsea; Analgesics; Animals; Plant Extracts; Pain; Humans
PubMed: 38731572
DOI: 10.3390/molecules29092079 -
BMC Emergency Medicine Sep 2023BACKGROUND: Treatment of acute pain is an essential element of pre-hospital care for injured and critically ill patients. Clinical studies indicate the need for...
ABSTRAC
BACKGROUND: Treatment of acute pain is an essential element of pre-hospital care for injured and critically ill patients. Clinical studies indicate the need for improvement in the prehospital analgesia.
OBJECTIVE
The aim of this study is to assess the current situation in out of hospital pain management in Germany regarding the substances, indications, dosage and the delegation of the use of analgesics to emergency medical service (EMS) staff.
MATERIAL AND METHODS
A standardized survey of the medical directors of the emergency services (MDES) in Germany was carried out using an online questionnaire. The anonymous results were evaluated using the statistical software SPSS (Chi-squared test, Mann-Whitney-U test).
RESULTS
Seventy-seven MDES responsible for 989 rescue stations and 397 EMS- physician bases in 15 federal states took part in this survey. Morphine (98.7%), Fentanyl (85.7%), Piritramide (61%), Sufentanil (18.2%) and Nalbuphine (14,3%) are provided as opioid analgesics. The non-opioid analgesics (NOA) including Ketamine/Esketamine (98,7%), Metamizole (88.3%), Paracetamol (66,2%), Ibuprofen (24,7%) and COX-2-inhibitors (7,8%) are most commonly available. The antispasmodic Butylscopolamine is available (81,8%) to most rescue stations. Fentanyl is the most commonly provided opioid analgesic for treatment of a traumatic pain (70.1%) and back pain (46.8%), Morphine for visceral colic-like (33.8%) and non-colic pain (53.2%). In cases of acute coronary syndrome is Morphine (85.7%) the leading analgesic substance. Among the non-opioid analgesics is Ketamine/Esketamine (90.9%) most frequently provided to treat traumatic pain, Metamizole for visceral colic-like (70.1%) and non-colic (68.6%) as well as back pain (41.6%). Butylscopolamine is the second most frequently provided medication after Metamizole for "visceral colic-like pain" (55.8%). EMS staff (with or without a request for presence of the EMS physician on site) are permitted to use the following: Morphine (16.9%), Piritramide (13.0%) and Nalbuphine (10.4%), and of NOAs for (Es)Ketamine (74.1%), Paracetamol (53.3%) and Metamizole (35.1%). The dosages of the most important and commonly provided analgesic substances permitted to independent treatment by the paramedics are often below the recommended range for adults (RDE). The majority of medical directors (78.4%) of the emergency services consider the independent application of analgesics by paramedics sensible. The reason for the relatively rare authorization of opioids for use by paramedics is mainly due to legal (in)certainty (53.2%).
CONCLUSION
Effective analgesics are available for EMS staff in Germany, the approach to improvement lies in the area of application. For this purpose, the adaptations of the legal framework as well as the creation of a guideline for prehospital analgesia are useful.
Topics: Adult; Humans; Ketamine; Analgesics, Non-Narcotic; Dipyrone; Acetaminophen; Nalbuphine; Pirinitramide; Butylscopolammonium Bromide; Physician Executives; Analgesics; Analgesics, Opioid; Fentanyl; Germany; Acute Pain; Morphine Derivatives
PubMed: 37710177
DOI: 10.1186/s12873-023-00878-8