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1.
BMC Palliat Care ; 22(1): 4, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36609269

RESUMO

BACKGROUND: Limited efficacy has been observed when using opioids to treat neuropathic pain. Lidocaine patches reduce neuropathic pain in postherpetic neuralgia, but their benefits for cancer-related neuropathic pain remain unclear. This study aimed to investigate a treatment for cancer-related neuropathic pain. METHODS: We conducted a prospective, open-label, single-arm study to assess the efficacy and safety of lidocaine transdermal patches in patients experiencing localized, superficial, neuropathic cancer pain. Terminal cancer patients already receiving opioid treatment participated in the 3-day study. The primary endpoint was pain intensity evaluated by the numerical rating scale (NRS). The secondary endpoints were the pain relief score and the quality of analgesic treatment. RESULTS: The results showed a significant difference in the median NRS over 3 days (Kruskal-Wallis test, p < 0.0001). The median NRS pain intensity from Day 1 to Day 3 was 4.0 with 95% C.I. (3.3, 5.0), 3.0 (2.5, 3.5), and 2.6 (2.0, 3.0), respectively. The difference between the median NRS pain intensities of any 2 days was significant (Wilcoxon signed-rank test, p < 0.0001). The generalized estimating equation (GEE) estimation model showed significant differences between the NRS pain intensities on any 2 days. There was no significant difference in the pain relief score or the quality of analgesic treatment. CONCLUSIONS: In this study, the 5% lidocaine transdermal patch reduced the NRS pain intensity in neuropathic cancer patients already receiving opioid treatment. Treatment of localized and superficial neuropathic pain caused by cancer was well tolerated and effective.


Assuntos
Neoplasias , Neuralgia , Humanos , Lidocaína/uso terapêutico , Lidocaína/efeitos adversos , Analgésicos Opioides/uso terapêutico , Medição da Dor , Estudos Prospectivos , Adesivo Transdérmico , Neuralgia/etiologia , Neuralgia/induzido quimicamente , Analgésicos/uso terapêutico , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Resultado do Tratamento
2.
Trials ; 24(1): 13, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36609307

RESUMO

BACKGROUND: Although opioids are commonly prescribed in clinical anaesthesia, the significant side effects attributed to their overuse are raising increasing concerns. One way to reduce perioperative opioid consumption is to apply opioid-reduced anaesthesia (ORA) and even opioid-free anaesthesia (OFA), which involves regional techniques, neuraxial anaesthesia, nonopioid analgesics or combined use. The aim of this study was to investigate whether the application of OFA by using esketamine in intraoperative analgesia could minimize the side effects of postoperative nausea and vomiting (PONV), as well as other short-term side effects related to anaesthesia. METHODS/DESIGN: The study was designed as a prospective, randomized, controlled, multicentre trial. A total of 278 patients were enrolled; participants were nonsmoking female patients aged 18-50 years and scheduled for laparoscopic appendectomy or cholecystectomy, ASA at I-III, with no serious physical or mental diseases. Both groups received usual perioperative care except for the analgesic medication of either esketamine or sufentanil. The primary outcome was the incidence of PONV 3 days after surgery. Secondary outcomes included recovery status, pain, sedation level and overall recovery, delirium and cognition, anxiety and depression and total consumption of analgesic agents. DISCUSSION: This trial may show that the synergy of esketamine and propofol anaesthesia reduces PONV as well as other short-term adverse events, thereby providing a better safety and satisfaction profile of ERAS for laparoscopic appendectomy and cholecystectomy. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100047169. Registered on June 9, 2021.


Assuntos
Anestesia , Laparoscopia , Humanos , Feminino , Náusea e Vômito Pós-Operatórios/prevenção & controle , Analgésicos Opioides/efeitos adversos , Estudos Prospectivos , Analgésicos/uso terapêutico , Laparoscopia/efeitos adversos , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
3.
Int J Colorectal Dis ; 38(1): 4, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36609578

RESUMO

PURPOSE: To evaluate the clinical efficacy and safety of different analgesic interventions in the treatment of pain after open hemorrhoidectomy by systematic review and network meta-analysis. METHODS: Randomized controlled trials that met the inclusion criteria in PubMed, Cochrane Library, Embase, Web of Science, Scopus, CNKI, WANFANG DATA, and VIP were searched from the date of database construction to June 28, 2022. RESULTS: Among the 13 randomized controlled trials (RCTs), 731 patients were included in the network meta-analysis. Most interventions are more effective than placebo in relieving postoperative pain. 24 h postoperative Visual Analogue Scale (VAS): glyceryl trinitrate (GTN) (mean difference (MD) - 4.20, 95% CI - 5.35, - 3.05), diltiazem (MD - 1.97, 95% CI - 2.44, - 1.51), botulinum toxin (BT) (MD - 1.50, 95% CI - 2.25, - 0.75), sucralfate (MD - 1.01, 95% CI - 1.53, - 0.49), and electroacupuncture (EA) (MD - 0.45, 95% CI - 0.87, - 0.04). 48 h postoperative VAS: diltiazem (MD - 2.45, 95% CI - 2.74, - 2.15), BT (MD - 2.18, 95% CI - 2.52, - 1.84), and sucralfate (MD - 1.41, 95% CI - 1.85, - 0.97). 7 d postoperative VAS: diltiazem (MD - 2.49, 95% CI - 3.20, - 1.78) and sucralfate (MD - 1.42, 95% CI - 2.00, - 0.85). The first postoperative defecation VAS: EA (MD - 0.70, 95% CI - 0.95, - 0.46). There are few data on intervention safety, and additional high-quality RCTs are expected to study this topic in the future. CONCLUSION: Diltiazem ointment may be the most effective medication for pain relief following open hemorrhoidectomy, and it can dramatically reduce pain within one week of surgery. The second and third recommended medications are BT and sucralfate ointment. GTN has a significant advantage in alleviating pain 24 h after open hemorrhoidectomy, but whether it causes headache is debatable; thus, it should be used with caution. EA's analgesic efficacy is still unknown. There was limited evidence on the safety of the intervention in this study, and it was simply presented statistically.


Assuntos
Hemorroidectomia , Humanos , Hemorroidectomia/efeitos adversos , Diltiazem/efeitos adversos , Pomadas/uso terapêutico , Sucralfato/uso terapêutico , Metanálise em Rede , Analgésicos/efeitos adversos , Nitroglicerina/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Molecules ; 28(2)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36677775

RESUMO

The natural product Salvinorin A (SalA) was the first nitrogen-lacking agonist discovered for the opioid receptors and exhibits high selectivity for the kappa opioid receptor (KOR) turning SalA into a promising analgesic to overcome the current opioid crisis. Since SalA's suffers from poor pharmacokinetic properties, particularly the absence of gastrointestinal bioavailability, fast metabolic inactivation, and subsequent short duration of action, the rational design of new tailored analogs with improved clinical usability is highly desired. Despite being known for decades, the binding mode of SalA within the KOR remains elusive as several conflicting binding modes of SalA were proposed hindering the rational design of new analgesics. In this study, we rationally determined the binding mode of SalA to the active state KOR by in silico experiments (docking, molecular dynamics simulations, dynophores) in the context of all available mutagenesis studies and structure-activity relationship (SAR) data. To the best of our knowledge, this is the first comprehensive evaluation of SalA's binding mode since the determination of the active state KOR crystal structure. SalA binds above the morphinan binding site with its furan pointing toward the intracellular core while the C2-acetoxy group is oriented toward the extracellular loop 2 (ECL2). SalA is solely stabilized within the binding pocket by hydrogen bonds (C210ECL2, Y3127.35, Y3137.36) and hydrophobic contacts (V1182.63, I1393.33, I2946.55, I3167.39). With the disruption of this interaction pattern or the establishment of additional interactions within the binding site, we were able to rationalize the experimental data for selected analogs. We surmise the C2-substituent interactions as important for SalA and its analogs to be experimentally active, albeit with moderate frequency within MD simulations of SalA. We further identified the non-conserved residues 2.63, 7.35, and 7.36 responsible for the KOR subtype selectivity of SalA. We are confident that the elucidation of the SalA binding mode will promote the understanding of KOR activation and facilitate the development of novel analgesics that are urgently needed.


Assuntos
Diterpenos Clerodânicos , Receptores Opioides kappa , Humanos , Receptores Opioides kappa/metabolismo , Diterpenos Clerodânicos/química , Receptores Opioides , Analgésicos , Analgésicos Opioides/química
5.
Pharm Biol ; 61(1): 201-212, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36628487

RESUMO

CONTEXT: Dolichos trilobus 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 D. trilobus 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 GABAA1 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.


Assuntos
Analgésicos , Extratos Vegetais , Animais , Camundongos , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Dor/tratamento farmacológico , Dor/induzido quimicamente , Extratos Vegetais/farmacologia
6.
PLoS One ; 18(1): e0280593, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36662848

RESUMO

BACKGROUND: Pregabalin is a drug used to treat neuropathic pain, and its use has increased substantially since 2007. Early trials found a strong treatment effect on pain for post-herpetic neuralgia and diabetic neuropathy. However more recent studies have failed to replicate these results. METHODS: This meta-epidemiological study aimed to assess change in the reported effectiveness of pregabalin in neuropathic pain trials over time, and if a change is present, determine any associated factors. DATA SOURCES: We performed electronic searches for published trials in Medline, Embase and Cochrane Central Register of Controlled Trials databases; and unpublished trials on ClinicalTrials.gov, the EU Clinical Trials Register, and the Australia New Zealand Clinical Trials Registry with no restrictions. STUDY SELECTION: We included randomized, placebo-controlled trials of pregabalin for treatment of neuropathic pain in adults. DATA EXTRACTION AND SYNTHESIS: Two authors independently extracted study data: sample size and mean baseline, end-point and change in pain scores with measures of variance, trial end year, publication year, clinical indication, funding source, country of study, treatment duration, treatment dose, mean age and percentage male. PRIMARY OUTCOME MEASURE: We defined treatment effect as the mean difference in pain scores between pregabalin and placebo groups at trial end-point and assessed for change over time using a random-effects meta-regression, adjusted for sample size, indication, treatment duration (weeks) and treatment dose. RESULTS: We included 38 randomized published trials (9038 participants) and found that between 2003 and 2020, the reported treatment effect of pregabalin decreased by 0.4 points (95% CI: 0.3 to 0.6; p<0.001) on an 11-point pain scale per 5-year interval, from 1.3 points (95% CI: 1.0 to 1.5) in trials conducted in 2001-2005, to 0.3 (95% CI: -0.1 to 0.7) in trials conducted in 2016-2020. The reported treatment effect was lower than the minimal clinically important difference (MCID) of 1.7 points across all time periods, doses and most indications and was not found to be associated with study characteristics. CONCLUSIONS: The reported treatment effect or analgesic efficacy of pregabalin from clinical trials has diminished over time. Clinical recommendations may need to be re-evaluated to account for recent evidence and to consider whether pregabalin therapy is indicated.


Assuntos
Neuropatias Diabéticas , Neuralgia Pós-Herpética , Neuralgia , Adulto , Humanos , Masculino , Analgésicos/uso terapêutico , Neuropatias Diabéticas/tratamento farmacológico , Neuropatias Diabéticas/epidemiologia , Neuralgia/tratamento farmacológico , Neuralgia/epidemiologia , Neuralgia Pós-Herpética/tratamento farmacológico , Neuralgia Pós-Herpética/epidemiologia , Pregabalina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Molecules ; 28(2)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36677821

RESUMO

B. crassifolia is a species that grows in various areas of Latin America. It was known to be useful for the treatment of different human ailments. The present work evaluated the neuropharmacological and analgesic effects of hydroalcoholic and dichloromethane extracts of B. crassifolia. The effect on the central nervous system (CNS) of both extracts obtained from bark, administered by the intraperitoneal route in mice, was evaluated by different tests: spontaneous motor activity, hole-board, motor coordination, pentobarbital induced hypnosis, and rectal temperature. Analgesic activity was evaluated using a hot plate test. Phytochemical analysis was performed by high-performance liquid chromatography (HPLC) using reversed-phase and gradient of elution. The hydroalcoholic extract (dose 0.5 g dry plant/kg weigh) administration caused an important reduction of the head-dipping response in the hole board test. A decrease in spontaneous motor activity test and a disturbance of motor coordination in the rotarod test was observed. The hydroalcoholic extract produced a significant prolongation of pentobarbital induced sleeping time. This extract prevented hot plate test induced nociception. The phytochemical analysis revealed the presence of catechin, epicatechin, and procyanidin B12. Therefore, this study revealed that the hydroalcoholic extract of B. crassifolia possesses analgesic and sedative CNS activity.


Assuntos
Pentobarbital , Extratos Vegetais , Humanos , Camundongos , Animais , Extratos Vegetais/química , Pentobarbital/farmacologia , Cromatografia Líquida de Alta Pressão , Atividade Motora , Casca de Planta , Comportamento Animal , Analgésicos/farmacologia , Modelos Animais
9.
J Coll Physicians Surg Pak ; 33(1): 5-9, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36597226

RESUMO

OBJECTIVE: To compare intravenous lidocaine infusion adjunct to NSAID and Acetaminophen with regular analgesics for postoperative mean pain score and mean ambulation time after laparoscopic cholecystectomy. STUDY DESIGN: Randomised controlled trial. PLACE AND DURATION OF STUDY: Department of General Surgery, Islamabad Medical Complex, (IMC), from March 2020 to December 2021. METHODOLOGY: Sixty (n=60) adult patients, both males and females between the ages of 18-60 years planned for laparoscopic cholecystectomy, were selected and randomly allocated to two groups of treatment (Lidocaine and Ringer Lactate). The control group did not receive any other placebo other than Ringer Lactate infusion. Both groups received Intramuscular Diclofenac 12 hourly and intravenous acetaminophen infusion 8 hourly. Postoperative pain 2, 6, 12 and 24 hours (h) and mean ambulation time were compared in both groups. RESULTS: Mean VAS (Visual Analogue Scale) of group 1 versus group 2 at 2 h, 6 h, 12 h and 24 h were 3.47 ± 0.82 vs. 6.27 ± 0.52 (p=<0.001), 2.7 ± 0.75 vs. 4.8 ± 0.8 (p<0.001), 2.0 ± 0.49 vs. 3.93 ± 0.94 (p<0.001), 0.73 ± 0.82 vs. 2.2 ± 0.61 (p<0.001). Time for spontaneous ambulation after surgery was 5.57 ± 1.55 hours for Group 1 versus 7.3 ± 1.9 hours for Group 2 (p<0.001). CONCLUSION: Pain scores at all-time intervals were lower, and ambulation time was shorter in patients who received intravenous infusion of lidocaine as compared to patients who received only regular analgesics for laparoscopic cholecystectomy. KEY WORDS: Ambulation time, Laparoscopic cholecystectomy, Postoperative pain.


Assuntos
Anestésicos Locais , Colecistectomia Laparoscópica , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Acetaminofen/uso terapêutico , Analgésicos/uso terapêutico , Analgésicos Opioides , Colecistectomia , Colecistectomia Laparoscópica/efeitos adversos , Método Duplo-Cego , Infusões Intravenosas , Lactatos , Lidocaína , Dor Pós-Operatória/tratamento farmacológico
10.
Neurosciences (Riyadh) ; 28(1): 13-18, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36617449

RESUMO

Medication-overuse headache (MOH) is a disabling secondary headache disorder, with challenging consequences for affected patients and health care resources. It is defined as headache that occurs on ≥ 15 days per month in a patient known to have primary headache disorder due to regular overuse of acute or abortive headache medication for more than 3 months. MOH affects 1-2% of the world's population in their productive age. New advances in headache neurosciences and development of new treatment options specific for headache, along with an understanding of the clinical profile and pathophysiological mechanisms of MOH, can help improve patient outcomes and decrease the burden on the health care system. This work will review MOH, identify updated clinical assessments and recent management approaches.


Assuntos
Transtornos da Cefaleia Secundários , Humanos , Transtornos da Cefaleia Secundários/diagnóstico , Transtornos da Cefaleia Secundários/terapia , Transtornos da Cefaleia Secundários/epidemiologia , Cefaleia/tratamento farmacológico , Analgésicos/efeitos adversos
11.
Agri ; 35(1): 16-21, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36625186

RESUMO

OBJECTIVES: Disorders in the cervical muscles, such as myofascial trigger points and tightness, are common factors in patients with cervicogenic headache (CEH). We aimed to evaluate the effectiveness of ultrasound-guided interfascial blocks of the trapezius muscle in patients with CEH who showed tenderness in the upper cervical muscle groups. METHODS: A total of 23 patients were evaluated in the prospective observational trial. The injection was performed between the trapezius muscle and levator scapula muscle fascia with a disposable 25-gauge, 10-cm Quincke-tip spinal needle. 10 mL of 0.125% bupivacaine was injected between the muscle fascia. Numeric rating scale (NRS), neck disability index (NDI), pain frequency, and analgesic consumption in the pre-treatment and post-treatment period were evaluated. RESULTS: The NRS scores at 10 min, 1 week, 2 weeks, and 4 weeks after treatment were significantly better than the pre-treatment NRS score. The NDI scores at 1, 2, and 4 weeks after treatment were significantly better than the pre-treatment NDI score. The pain frequency at 1 and 2 weeks after treatment was significantly lower than that recorded in the pre-treatment period. Statistically significant reductions were observed in analgesic consumption at 1, 2, and 4 weeks after treatment, in comparison with consumption in the pre-treatment period. CONCLUSION: We suggest that an ultrasound-guided interfascial block of the trapezius muscle is effective for the treatment of CEH caused by muscle disorders.


Assuntos
Cefaleia Pós-Traumática , Músculos Superficiais do Dorso , Humanos , Ultrassonografia de Intervenção , Analgésicos , Dor
12.
Mymensingh Med J ; 32(1): 90-95, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36594307

RESUMO

Control of pain in patients with chronic pancreatitis is difficult because 30.0% to 50.0% of patients still experience persistence or recurrence of pain even after surgery. So a combined approach of surgery and coeliac plexus neurolysis was carried out in this study to see the relief of pain and reduce the requirement of analgesics in these patients. This prospective observational comparative study was carried out in the Department of Hepatobiliary, Pancreatic and Liver Transplant Surgery in Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from November 2017 to October 2018. Forty one (41) study participants with the diagnosis of chronic pancreatitis were included consecutively in this study. The participants were divided into two groups. Group I (n=18) underwent pancreatic surgery with coeliac plexus neurolysis by infiltration of 20ml of 100% alcohol in the loose areolar tissue 10ml each into right and left para-aortic space at the level of coeliac trunk and Group II (n=23) underwent pancreatic surgery only. Participants' preoperative data were collected from patient record file. Number, frequency and intensity of pain and requirement of amount of analgesics for the last 3 months were recorded from patients' history. The intensity of pain was categorized by visual analog scale (VAS) preoperatively. The participants of both groups were followed up at 1, 2 and 3 months interval and asked for disappearance or reduction of pain, frequency of attack and requirement of analgesics. Again visual analog scale was used for categorization of pain. Pain free period was recorded after the end of follow up period. Pain reduction occurred after surgery in both groups. But when pain relief was compared on the basis of VAS (Visual Analogue Scale), it was significantly better in Group I after 1 month of surgery than Group II (p=0.05). But 2 and 3 months after surgery this difference became insignificant (p=0.246 and 0.264). No statistical difference was found in terms of analgesic usage, severe acute attack or hospital admission (p=0.511, 0.439 and 0.495) at the end of 3 months follow up. Participants in Group I had significantly longer pain free period than Group II (p=0.025). Regarding complications, postural hypotension developed in 5.6% (1) patients. Diarrhea developed in 11.1% (2) patients in Group I and wound infection developed in 2 patients in each groups respectively. No patients developed any major complications like anastomotic leakage, deep or organ or space infection. Intraoperative coeliac plexus neurolysis reduces pain immediately after surgery and provides longer pain free period in patients with chronic pancreatitis after surgery.


Assuntos
Plexo Celíaco , Pancreatite Crônica , Humanos , Plexo Celíaco/cirurgia , Bangladesh , Pancreatite Crônica/complicações , Pancreatite Crônica/cirurgia , Analgésicos/uso terapêutico , Dor Pós-Operatória/etiologia
13.
Nat Commun ; 14(1): 4, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36596769

RESUMO

Transient receptor potential vanilloid 1 (TRPV1) ion channel is a classic analgesic target, but antagonists of TRPV1 failed in clinical trials due to their side effects like hyperthermia. Here we rationally engineer a peptide s-RhTx as a positive allosteric modulator (PAM) of TRPV1. Patch-clamp recordings demonstrate s-RhTx selectively potentiated TRPV1 activation. s-RhTx also slows down capsaicin-induced desensitization of TRPV1 in the presence of calcium to cause more calcium influx in TRPV1-expressing cells. In addition, our thermodynamic mutant cycle analysis shows that E652 in TRPV1 outer pore specifically interacts with R12 and K22 in s-RhTx. Furthermore, we demonstrate in vivo that s-RhTx exhibits long-lasting analgesic effects in noxious heat hyperalgesia and CFA-induced chronic inflammatory pain by promoting the reversible degeneration of intra-epidermal nerve fiber (IENF) expressing TRPV1 channels in mice, while their body temperature remains unaffected. Our results suggest s-RhTx is an analgesic agent as a PAM of TRPV1.


Assuntos
Analgesia , Canais de Potencial de Receptor Transitório , Camundongos , Animais , Cálcio , Canais de Cátion TRPV/genética , Dor/tratamento farmacológico , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Capsaicina/farmacologia , Peptídeos/farmacologia , Peptídeos/uso terapêutico
14.
J Appl Oral Sci ; 30: e20220304, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36629536

RESUMO

BACKGROUND: Nociceptive and inflammatory orofacial pain is highly prevalent in the population, which justifies the search for safer analgesics. There is increasing evidence of the analgesic and anxiolytic potential of Lavandula angustifolia essential oil (LAV EO), which may represent, when administered through inhalation, may represent a safer alternative for pain treatment. OBJECTIVE: to evaluate whether LAV EO has antinociceptive effect in the formalin test, and anti-hyperalgesic and anxiolytic-like effects in rats subjected to a model of orofacial postoperative pain. METHODOLOGY: Female Wistar rats were exposed to LAV EO (5%) by inhalation for 30 minutes. After exposure, animals were injected with formalin (2.5%, 50 µL) or saline into the hind paw or upper lip and the number of flinches or facial grooming time, respectively, were evaluated. Likewise, on day 3 after intraoral mucosa incision, the animals were exposed to LAV EO and facial mechanical, and heat hyperalgesia were assessed. The influence of LAV EO inhalation on anxiety-like behavior was assessed in operated rats by testing them on the open field (OF) and elevated plus maze (EPM). RESULTS: LAV EO reduced the phase II of the paw formalin test and both phases of the orofacial formalin test. On day three post-incision, LAV EO reduced heat and mechanical hyperalgesia, from 30 minutes up to three hours, and reduced the anxiety-like behavior in operated rats without causing locomotor deficit. CONCLUSION: LAV EO inhalation results in antinociceptive and anxiolytic-like effects in orofacial pain models, which encourages further studies on LAV EO indications and effectiveness on orofacial pain conditions.


Assuntos
Ansiolíticos , Lavandula , Óleos Voláteis , Ratos , Feminino , Animais , Ansiolíticos/farmacologia , Ansiolíticos/uso terapêutico , Ratos Wistar , Dor Facial/tratamento farmacológico , Analgésicos/farmacologia , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico
15.
BMC Anesthesiol ; 23(1): 22, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36639747

RESUMO

PURPOSE: The simultaneous use of drugs with different mechanisms of analgesic action is a strategy for achieving effective pain control while minimizing dose-related side effects. Choline was described to potentiate the analgesic action of parecoxib sodium at small doses in several inflammatory pain models. However, these findings are still very limited, and more associated data are required to confirm the effectiveness of the combined choline and parecoxib sodium therapy against inflammatory pain. METHODS: Adult rats were randomly divided into 9 groups (N = 6/group). The sham surgery group received an intraperitoneal (i.p.) injection of saline. Rats with chronic constriction injury (CCI) of the sciatic nerve received saline, choline (cho, 6, 12 and 24 mg/kg), parecoxib sodium (pare, 3, 6, and 12 mg/kg), or a combination of choline 6 mg/kg and parecoxib sodium 3 mg/kg. Mechanical and heat pain thresholds were measured at 30 min after drug treatment at Days 3, 5, 7, 10, and 14 after CCI. Another 30 rats were divided into 5 groups (N = 6/group): the sham, CCI + saline, CCI + cho-6 mg/kg, CCI + pare-3 mg/kg, and CCI + cho-6 mg/kg + pare-3 mg/kg groups. After repeated drug treatment for 7 days, five rats were randomly selected from each group, and the lumbar dorsal root ganglia (DRGs) (L4-6) were harvested for western blot analysis. RESULTS: Choline significantly attenuated mechanical and heat hypersensitivity in CCI rats at 12 and 24 mg/kg doses (P < 0.05) but was not effective at the 6 mg/kg dose. Parecoxib sodium exerted significant pain inhibitory effects at the 6 and 12 mg/kg doses (P < 0.05) but not at the 3 mg/kg dose. Combining a low dose of choline (6 mg/kg) and parecoxib sodium (3 mg/kg) produced significant pain inhibition in CCI rats and reduced the expression of high mobility group protein 1 (HMGB1) and nuclear factor-kappa Bp65 (NF-κBp65) in L4-6 DRGs. CONCLUSION: 1. In a rat model of chronic neuropathic pain (CCI), at a certain dose, choline or parecoxib sodium can alleviate mechanical pain and thermal hyperalgesia caused by CCI. 2. The combination of choline and parecoxib sodium in nonanalgesic doses can effectively relieve neuropathic pain, and its mechanism may be related to the inhibition of the high mobility group protein 1 (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway.


Assuntos
Colina , Isoxazóis , Neuralgia , Animais , Ratos , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Constrição , Proteína HMGB1 , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Neuralgia/tratamento farmacológico , Neuralgia/etiologia , Ratos Sprague-Dawley , Nervo Isquiático , Colina/farmacologia , Isoxazóis/farmacologia
16.
Clin J Pain ; 39(2): 85-90, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36650604

RESUMO

OBJECTIVES: The optimal dosage of dexmedetomidine (DEX) for postoperative analgesia of quadratus lumborum block (QLB) after laparoscopic myomectomy is not clear. Our study evaluated the analgesic and adverse effects of different doses of locally administered DEX. MATERIALS AND METHODS: Patients underwent laparoscopic myomectomy were enrolled in this randomized controlled trial. Transmuscular bilateral QLB was conducted postoperatively using local anesthetic plus different doses of DEX, as an adjuvant, per side. Numeric rating scales (NRS) of pain score and heart rate (HR) were assessed after performing QLB. Additional analgesics through patient-controlled analgesia pump, recovery time to first flatus, hospital stay, and other outcomes were also compared. RESULTS: A total of 150 participants were randomly divided into 3 groups (DEX1 group: 0.1 µg/kg; DEX2 group: 0.3 µg/kg; DEX3 group: 0.5 µg/kg), 50 for each group. Compared with the DEX1 group, NRS pain scores were lower in groups DEX2 and DEX3 ( P <0.017) 20 minutes after QLB and the significance lasted for 24 hours. Patients in groups DEX2 and DEX3 needed fewer additional analgesics than the group DEX1 ( P <0.017). HR in groups DEX2 and DEX3 was lower than the group DEX1 10 minutes and 20 minutes after QLB, respectively ( P <0.017). Sixty minutes after QLB, HR in the DEX3 group was still lower than the other groups. More patients in the DEX3 group were found bradycardia. Satisfaction score of postoperative analgesia was higher in groups DEX2 and DEX3 than the DEX1 group ( P <0.017). DISCUSSION: The results suggest that solution of DEX 0.3 µg/kg in ropivacaine 0.25% for QLB is recommended to relieve postoperative pain after laparoscopic myomectomy effectively and safely.


Assuntos
Dexmedetomidina , Laparoscopia , Miomectomia Uterina , Feminino , Humanos , Dexmedetomidina/uso terapêutico , Miomectomia Uterina/efeitos adversos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Anestésicos Locais/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Analgésicos/uso terapêutico , Analgesia Controlada pelo Paciente , Analgésicos Opioides , Ultrassonografia de Intervenção/métodos
17.
Anesth Analg ; 136(2): 373-386, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36638515

RESUMO

BACKGROUND: Increasing attention has been attracted to the development of bifunctional compounds to minimize the side effects of opioid analgesics. Pharmacological studies have verified the functional interaction between opioid and cannabinoid systems in pain management, suggesting that coactivation of the opioid and cannabinoid receptors may provide synergistic analgesia with fewer adverse reactions. Herein, we developed and characterized a novel bifunctional compound containing the pharmacophores of the mu-opioid receptor agonist DALDA and the cannabinoid peptide VD-Hpα-NH2, named OCP002. METHODS: The opioid and cannabinoid agonistic activities of OCP002 were investigated in calcium mobilization and western blotting assays, respectively. Moreover, the central and peripheral antinociceptive effects of OCP002 were evaluated in mouse preclinical models of tail-flick test, carrageenan-induced inflammatory pain, and acetic acid-induced visceral pain, respectively. Furthermore, the potential opioid and cannabinoid side effects of OCP002 were systematically investigated in mice after intracerebroventricular (ICV) and subcutaneous (SC) administrations. RESULTS: OCP002 functioned as a mixed agonist toward mu-opioid, kappa-opioid, and cannabinoid CB1 receptors in vitro. ICV and SC injections of OCP002 produced dose-dependent antinociception in mouse models of nociceptive (the median effective dose [ED50] values with 95% confidence interval [CI] are 0.14 [0.12-0.15] nmol and 0.32 [0.29-0.35] µmol/kg for ICV and SC injections, respectively), inflammatory (mechanical stimulation: ED50 values [95% CI] are 0.76 [0.64-0.90] nmol and 1.23 [1.10-1.38] µmol/kg for ICV and SC injections, respectively; thermal stimulation: ED50 values [95% CI] are 0.13 [0.10-0.17] nmol and 0.23 [0.08-0.40] µmol/kg for ICV and SC injections, respectively), and visceral pain (ED50 values [95% CI] are 0.0069 [0.0050-0.0092] nmol and 1.47 [1.13-1.86] µmol/kg for ICV and SC injections, respectively) via opioid and cannabinoid receptors. Encouragingly, OCP002 cannot cross the blood-brain barrier and exerted nontolerance-forming analgesia over 6-day treatment at both supraspinal and peripheral levels. Consistent with these behavioral results, repeated OCP002 administration did not elicit microglial hypertrophy and proliferation, the typical features of opioid-induced tolerance, in the spinal cord. Furthermore, at the effective analgesic doses, SC OCP002 exhibited minimized opioid and cannabinoid side effects on motor performance, body temperature, gastric motility, physical and psychological dependence, as well as sedation in mice. CONCLUSIONS: This study demonstrates that OCP002 produces potent and nontolerance-forming antinociception in mice with reduced opioid- and cannabinoid-related side effects, which strengthen the candidacy of bifunctional drugs targeting opioid/cannabinoid receptors for translational-medical development to replace or assist the traditional opioid analgesics.


Assuntos
Analgésicos , Agonistas de Receptores de Canabinoides , Canabinoides , Receptores Opioides , Dor Visceral , Animais , Camundongos , Analgésicos/farmacologia , Analgésicos Opioides , Relação Dose-Resposta a Droga , Receptores de Canabinoides , Receptores Opioides/agonistas , Dor Visceral/induzido quimicamente , Dor Visceral/tratamento farmacológico , Agonistas de Receptores de Canabinoides/farmacologia
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