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1.
Medicine (Baltimore) ; 99(35): e21449, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871867

RESUMO

BACKGROUND: Pulsed electromagnetic fields shows some potential in alleviating pain after mammaplasty. This systematic review and meta-analysis is conducted to investigate the analgesic efficacy of pulsed electromagnetic fields for pain control after mammaplasty. METHODS: The databases including PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases are systematically searched for collecting the randomized controlled trials regarding the impact of pulsed electromagnetic fields on pain intensity after mammaplasty. RESULTS: This meta-analysis has included 4 randomized controlled trials. Compared with control group after mammaplasty, pulsed electromagnetic fields results in remarkably reduced pain scores on 1 day (MD = -1.34; 95% confidence interval [CI] = -2.23 to -0.45; P = .003) and 3 days (MD = -1.86; 95% CI = -3.23 to -0.49; P = .008), as well as analgesic consumption (Std. MD = -5.64; 95% CI = -7.26 to -4.02; P < .00001). CONCLUSIONS: Pulsed electromagnetic fields is associated with substantially reduced pain intensity after mammaplasty.


Assuntos
Mama/cirurgia , Campos Eletromagnéticos/efeitos adversos , Mamoplastia/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Adolescente , Adulto , Idoso , Analgésicos/farmacologia , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Manejo da Dor/métodos , Dor Pós-Operatória/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
2.
Braz J Med Biol Res ; 53(10): e10204, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32901685

RESUMO

Several isatin derivatives have shown important biological activities, which have attracted interest from researchers. For this reason, the present study aimed to evaluate the anti-inflammatory and antinociceptive effects of the isatin derivative (Z)-2-(5-chloro-2-oxoindolin-3-ylidene)-N-phenyl-hydrazinecarbothioamide (COPHCT) in mice. Three doses of this compound were tested: 1.0, 2.5, and 5.0 mg/kg. The anti-inflammatory activity was assessed using the carrageenan-induced paw edema model and the zymosan-induced air pouch model. The evaluation of the antinociceptive effect was performed through the formalin test and the acetic acid-induced abdominal writhing test. The paw edema assay demonstrated that all doses of the compound showed a significant reduction of the edema in the second hour evaluated, but a better response was observed in the fourth hour. The zymosan-induced air pouch model indicated that the compound, in all doses, significantly reduced leukocyte migration and total protein concentration levels. In the formalin test, the doses 1.0, 2.5, and 5.0 mg/kg of COPHCT showed activity only in the second phase, with reduction in paw pain time of 73.61, 79.46, and 73.85%, respectively. The number of abdominal writhings decreased with the increasing dose, but only 5.0 mg/kg COPHCT exhibited a significant response, with a reduction of 24.88%. These results demonstrated the ability of this compound to interfere in the anti-inflammatory activity of edema, vascular permeability, and cell migration. In addition, its possible antinociceptive effect may be related to the dose used.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Isatina/farmacologia , Animais , Carragenina , Edema , Feminino , Masculino , Camundongos , Extratos Vegetais
3.
Chem Biol Interact ; 330: 109178, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32738201

RESUMO

The capsaicin (vanilloid) receptor, TRPV1, is a heat-activated cation channel modulated by inflammatory mediators and contributes to acute and chronic pain. TRPV1 channel is one of the most researched and targeted mechanisms for the development of novel analgesics. Over the years, natural products have contributed enormously to the development of important therapeutic drugs used currently in modern medicine. A literature review was conducted using Medline, Google Scholar, and PubMed. Searching the literature resulted in listing 136 natural compounds that interacted with TRPV1 channel. These compounds were phytochemicals that belong to different chemical groups including vanilloids, flavonoids, alkaloids, terpenoids, terpenyl phenols, fatty acids, cannabinoids, sulfur_containing compounds, etc. Other natural TRPV1 modulators were of animal, fungal or bacterial origin. Some natural products were small agonists or antagonists of TRPV1. Others were protein venoms. Most in vitro studies utilized electrophysiological or calcium imaging techniques to study calcium flow through the channel using primary cultures of rat dorsal root and trigeminal ganglia. Other studies used hTRPV1 or rTRPV1 expressed in HEK239, CHO cells or Xenopus oocytes. In vivo studies concentrated on different pain models conducted mainly in mice and rats. In conclusion, natural products are highly diverse in their modulatory action on TRPV1. Many gaps in natural product research are present in distinguishing modality-specific from polymodal antagonists. Species' differences in TRPV1 functionality must be taken into account in any future study. Proceeding into clinical trials needs more efforts to discover potent TRPV1 antagonists devoid of hyperthermia, the main side effect.


Assuntos
Analgésicos/farmacologia , Produtos Biológicos/farmacologia , Canais de Cátion TRPV/metabolismo , Analgésicos/efeitos adversos , Analgésicos/uso terapêutico , Animais , Produtos Biológicos/efeitos adversos , Cálcio/metabolismo , Técnicas de Cultura de Células , Febre/etiologia , Humanos , Dor/complicações , Dor/tratamento farmacológico , Canais de Cátion TRPV/agonistas , Canais de Cátion TRPV/antagonistas & inibidores , Canais de Cátion TRPV/efeitos dos fármacos , Canais de Cátion TRPV/genética
4.
Curr Opin Anaesthesiol ; 33(5): 633-638, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32826629

RESUMO

PURPOSE OF REVIEW: Ketamine has been used for decades for a variety of indications. Beyond the historical benefits and effects of ketamine, newer developments have occurred worthy of an update. This review will discuss common uses and indications for ketamine in the perioperative setting, as well as highlight newer indications in recent years. RECENT FINDINGS: Multiple studies have examined the use of ketamine in a variety of environments, as ketamine has become more popular in emergency rooms and ICUs. Ketamine may be particularly beneficial in management of burn patients, who often require multiple procedures over the course of their treatment. Ketamine's role in the ongoing opioid crisis has been of particular interest, with multiple studies evaluating its potential role in managing both acute and chronic pain conditions. Ongoing studies examining the role of ketamine in treatment of depressions show promise as well. SUMMARY: Ketamine is regaining popularity in the field of anesthesia and beyond. New studies provide insight on the many indications and use that anesthesia providers may encounter during their perioperative care of patients. Ongoing research is needed to further elucidate ketamine's effects on the management of psychiatric conditions and potential indications for ketamine metabolites.


Assuntos
Analgesia , Analgésicos/farmacologia , Anestesia , Anestésicos Dissociativos/farmacologia , Queimaduras/tratamento farmacológico , Depressão/tratamento farmacológico , Ketamina/farmacologia , Dor/tratamento farmacológico , Humanos , Manejo da Dor , Período Perioperatório
5.
Br J Anaesth ; 125(4): 596-604, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32819621

RESUMO

BACKGROUND: A novel G-protein signalling-biased mu opioid peptide (MOP) receptor agonist, PZM21, was recently developed with a distinct chemical structure. It is a potent Gi/o activator with minimal ß-arrestin-2 recruitment. Despite intriguing activity in rodent models, PZM21 function in non-human primates is unknown. The aim of this study was to investigate PZM21 actions after systemic or intrathecal administration in primates. METHODS: Antinociceptive, reinforcing, and pruritic effects of PZM21 were compared with those of the clinically used MOP receptor agonists oxycodone and morphine in assays of acute thermal nociception, capsaicin-induced thermal allodynia, itch scratching responses, and drug self-administration in gonadally intact, adult rhesus macaques (10 males, six females). RESULTS: After subcutaneous administration, PZM21 (1.0-6.0 mg kg-1) and oxycodone (0.1-0.6 mg kg-1) induced dose-dependent thermal antinociceptive effects (P<0.05); PZM21 was 10 times less potent than oxycodone. PZM21 exerted oxycodone-like reinforcing effects and strength as determined by two operant schedules of reinforcement in the intravenous drug self-administration assay. After intrathecal administration, PZM21 (0.03-0.3 mg) dose-dependently attenuated capsaicin-induced thermal allodynia (P<0.05). Although intrathecal PZM21 and morphine induced MOP receptor-mediated antiallodynic effects, both compounds induced robust, long-lasting itch scratching. CONCLUSIONS: PZM21 induced antinociceptive, reinforcing, and pruritic effects similar to clinically used MOP receptor agonists in primates. Although structure-based discovery of PZM21 identified a novel avenue for studying G-protein signalling-biased ligands, biasing an agonist towards G-protein signalling pathways did not determine or alter reinforcing (i.e. abuse potential) or pruritic effects of MOP receptor agonists in a translationally relevant non-human primate model.


Assuntos
Analgésicos/farmacologia , Prurido/induzido quimicamente , Receptores Opioides mu/agonistas , Reforço Psicológico , Tiofenos/farmacologia , Ureia/análogos & derivados , Animais , Relação Dose-Resposta a Droga , Feminino , Macaca mulatta , Masculino , Ureia/farmacologia
6.
Fundam Clin Pharmacol ; 34(5): 530-547, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32603486

RESUMO

Patients with COVID-19 are sometimes already being treated for one or more other chronic conditions, especially if they are elderly. Introducing a treatment against COVID-19, either on an outpatient basis or during hospitalization for more severe cases, raises the question of potential drug-drug interactions. Here, we analyzed the potential or proven risk of the co-administration of drugs used for the most common chronic diseases and those currently offered as treatment or undergoing therapeutic trials for COVID-19. Practical recommendations are offered, where possible.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Medicamentos sob Prescrição/farmacologia , Analgésicos/farmacologia , Antiasmáticos/farmacologia , Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Anticoagulantes/farmacologia , Antineoplásicos/farmacologia , Antituberculosos/farmacologia , Antivirais/farmacologia , Betacoronavirus , Fármacos Cardiovasculares/farmacologia , Interações Medicamentosas , Humanos , Hidroxicloroquina/farmacologia , Hipoglicemiantes/farmacologia , Hipolipemiantes/farmacologia , Interferon beta-1b/farmacologia , Pandemias , Medicamentos sob Prescrição/farmacocinética , Psicotrópicos/farmacologia , Receptores de Interleucina/antagonistas & inibidores , Medição de Risco , Hormônios Tireóideos/farmacologia
7.
PLoS One ; 15(6): e0233711, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32492026

RESUMO

Animals that experience painful procedures as neonates are more sensitive to pain later in life. We evaluated whether disbudding with a heated iron at 3 (n = 12), 35 (n = 9), or 56 (n = 20) d of age affected heifers' pain responses to vaccine injections at 11 mo of age. Heifers responded to the injection procedure with struggling and changes in eye temperature and heart rate variability compared to a sham procedure the day before, and still had a heightened response 6 d later, regardless of disbudding age. However, some heart rate variability indices suggested increased sympathetic dominance in heifers disbudded at 35 d, compared to the other 2 age groups, independent of the injection procedure. We also found that heifers disbudded at 3 or 35 d had a higher mean heart rate after the injection procedure compared to those disbudded at 56 d. We conclude that: (1) heifers find injections aversive; and (2) there is some evidence that disbudding age influences autonomic nervous system activity later in life.


Assuntos
Comportamento Animal , Queimaduras/complicações , Dor/etiologia , Dor/prevenção & controle , Analgésicos/farmacologia , Criação de Animais Domésticos/métodos , Animais , Animais Recém-Nascidos , Bovinos , Estudos de Coortes , Feminino , Frequência Cardíaca , Cornos/crescimento & desenvolvimento , Injeções , Meloxicam/farmacologia , Vacinação , Vacinas/administração & dosagem
8.
PLoS One ; 15(6): e0234176, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32497151

RESUMO

Chronic neuropathic pain (NP) is a growing clinical problem for which effective treatments, aside from non-steroidal anti-inflammatory drugs and opioids, are lacking. Cannabinoids are emerging as potentially promising agents to manage neuroimmune effects associated with nociception. In particular, Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and their combination are being considered as therapeutic alternatives for treatment of NP. This study aimed to examine whether sex affects long-term outcomes on persistent mechanical hypersensitivity 7 weeks after ceasing cannabinoid administration. Clinically relevant low doses of THC, CBD, and a 1:1 combination of THC:CBD extracts, in medium chain triglyceride (MCT) oil, were orally gavaged for 14 consecutive days to age-matched groups of male and female sexually mature Sprague Dawley rats. Treatments commenced one day after surgically inducing a pro-nociceptive state using a peripheral sciatic nerve cuff. The analgesic efficacy of each phytocannabinoid was assessed relative to MCT oil using hind paw mechanical behavioural testing once a week for 9 weeks. In vivo intracellular electrophysiology was recorded at endpoint to characterize soma threshold changes in primary afferent sensory neurons within dorsal root ganglia (DRG) innervated by the affected sciatic nerve. The thymus, spleen, and DRG were collected post-sacrifice and analyzed for long-term effects on markers associated with T lymphocytes at the RNA level using qPCR. Administration of cannabinoids, particularly the 1:1 combination of THC, elicited a sustained mechanical anti-hypersensitive effect in males with persistent peripheral NP, which corresponded to beneficial changes in myelinated Aß mechanoreceptive fibers. Specific immune cell markers associated with T cell differentiation and pro-inflammatory cytokines, previously implicated in repair processes, were differentially up-regulated by cannabinoids in males treated with cannabinoids, but not in females, warranting further investigation into sexual dimorphisms that may underlie treatment outcomes.


Assuntos
Analgésicos/administração & dosagem , Analgésicos/farmacologia , Canabidiol/efeitos adversos , Canabidiol/farmacologia , Dronabinol/administração & dosagem , Dronabinol/farmacologia , Óleos/química , Administração Oral , Analgésicos/química , Animais , Biomarcadores/metabolismo , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Canabidiol/química , Dronabinol/química , Composição de Medicamentos , Interações Medicamentosas , Feminino , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley
9.
Vet J ; 259-260: 105471, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32553233

RESUMO

The neurotransmitter Substance P, and its neurokinin-1 receptor (NK-1R) are involved in the regulation of many pathophysiological processes including emesis, inflammation and nociceptive processing. This review provides a brief summary of the anti-inflammatory and analgesic properties of experimental NK-1R antagonists followed by a systematic review and meta-analysis on maropitant, the only NK-1R antagonist with a label indication for emesis in veterinary patients. There is very limited evidence based information on the putative clinical utilisation of maropitant for pain and inflammation. The aim of this systematic review and meta-analysis was to evaluate published reports on anti-inflammatory, analgesic and anaesthesia-sparing effects of maropitant. Medline, Pubmed, Science direct and Web of Science were searched to identify all published studies on maropitant, followed by a meta-analysis. Fourteen studies with 128 animals receiving maropitant and 127 controls met the inclusion criteria. Overall, maropitant had a significant inhalation anaesthetic-sparing effect (SMD -0.92, 95% CI -1.30, -0.54; P < 0.00001). However, treatment with maropitant had no effect on pain (SMD 0.06, 95% CI -0.37, 0.48; P = 0.80), or leukocyte cell infiltration in different inflammatory conditions (SMD -0.60, 95% CI -1.31, 0.11; P = 0.10). Based on all eligible studies for this review, it can be deduced that maropitant significantly reduced the minimum alveolar concentrations for isoflurane and sevoflurane for many different surgical procedures but it had no clearly proven effect on inflammation and pain.


Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Quinuclidinas/uso terapêutico , Analgésicos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Antagonistas do Receptor de Neuroquinina-1/farmacologia , Antagonistas do Receptor de Neuroquinina-1/uso terapêutico , Dor/tratamento farmacológico , Dor/veterinária , Quinuclidinas/farmacologia
10.
An Acad Bras Cienc ; 92(1): e20180793, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32401835

RESUMO

The therapeutic effects from Citrus reticulata on painful inflammatory ailments are associated to its flavonoids constituent and phytochemical studies with Citrus genus affirm that the peels have important amounts of it. These bioactive compounds have been a considerable therapeutic source and evaluate potential application of the peel extract is significant. This research aims to investigate the influence of ethanolic crude extract from the peels of Citrus reticulata and its possible mechanism of action in different animal models of pain. The extract reduced hyperalgesia in the second phase of formalin test (vehicle: 501.5 ± 40.0 s; C. reticulata extract 300 mg/kg: 161.8 ± 41.1 s), in the carrageenan model (vehicle at 4th h: 82.5 ± 9.6 %; C. reticulata extract 300 mg/kg at 4th h: 47.5 ± 6.5 %) and in Complete Freund's Adjuvant model (vehicle: 501.5 ± 40.0 s; C. reticulata extract 300 mg/kg: 161.8 ± 41.1 s). The possible contribution of opioidergic and adenosinergic systems in the anti-hyperalgesic effect of C. reticulata extract was observed after treatment, with non-selective antagonists for both systems, which produced reversal effects. In conclusion, these properties of C. reticulata extract suggest a potential therapeutic benefit in treating painful conditions.


Assuntos
Analgésicos/farmacologia , Citrus/química , Hiperalgesia/tratamento farmacológico , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Carragenina , Avaliação Pré-Clínica de Medicamentos , Etanol , Masculino , Camundongos , Medição da Dor , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/uso terapêutico , Extratos Vegetais/uso terapêutico
11.
Pain Res Manag ; 2020: 1876862, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32454918

RESUMO

Purified from the roots of the plant Sinomenium acutum, sinomenine is traditionally used in China and Japan for treating rheumatism and arthritis. Previously, we have demonstrated that sinomenine possessed a broad analgesic spectrum in various chronic pain animal models and repeated administration of sinomenine did not generate tolerance. In this review article, we discussed sinomenine's analgesic mechanism with focus on its role on immune regulation and neuroimmune interaction. Sinomenine has distinct immunoregulative properties, in which glutamate, adenosine triphosphate, nitric oxide, and proinflammatory cytokines are thought to be involved. Sinomenine may alter the unbalanced neuroimmune interaction and inhibit neuroinflammation, oxidative stress, and central sensitization in chronic pain states. In conclusion, sinomenine has promising potential for chronic pain management in different clinical settings.


Assuntos
Analgésicos/farmacologia , Dor Crônica , Morfinanos/farmacologia , Neuroimunomodulação/efeitos dos fármacos , Animais , Dor Crônica/tratamento farmacológico , Dor Crônica/fisiopatologia , Humanos
12.
J Cancer Res Ther ; 16(1): 34-39, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32362607

RESUMO

Background and Objective: Metformin (MET) has been used as an antidiabetic agent for type II diabetes. At the same time, recent researches have shown that the clinical improvement of MET is useful for nerve damage. In this study, we investigated the analgesic effect of MET in paclitaxel (PAC)-induced neuropathic pain. Materials and Methods: Forty-two adult, female rats, Wistar strain weighing 220 ± 10 g were randomly divided into 5 experimental groups. PAC was intraperitoneally (IP) administered (2.0 mg/kg) for 4 groups every other day (0, 2, 4, and 6 days). By the 30th day, MET (100, 200, and 400 mg/kg) was administered to 4 groups. Before and after treatment, basal pain threshold values were measured with Randall-Selitto analgesiometer test. At the end of experiment, pathological values were measured in selected regions including brain (motor cortex, M1), spinal cord (L4-L5), sciatic nerve, and muscle. Results: According to our results, PAC-induced neuropathic pain reached to highest level at 14th day. Four hundred milligram/kilogram concentration of MET remarkably decreased PAC-induced neuropathic pain. On the other hand, pathologic features have shown that PAC had significant pathological change in the brain and spinal cord while in the peripheral nerves and muscles had not shown any pathological change. Conclusion: The pathological results of the current study for the first time demonstrated that MET beside of its antidiabetic effects reversed neuropathic pain induced by PAC. Consequently, this research can be promising for cancer patients that suffering from neuropathic pain induced by anticancer drugs.


Assuntos
Analgésicos/farmacologia , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Neoplasias/complicações , Neuralgia/prevenção & controle , Paclitaxel/efeitos adversos , Limiar da Dor/efeitos dos fármacos , Animais , Antineoplásicos Fitogênicos/efeitos adversos , Modelos Animais de Doenças , Feminino , Neoplasias/patologia , Neuralgia/induzido quimicamente , Neuralgia/patologia , Ratos , Ratos Wistar
13.
Am J Vet Res ; 81(4): 299-308, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32228259

RESUMO

OBJECTIVE: To determine whether concurrent vatinoxan administration affects the antinociceptive efficacy of medetomidine in dogs at doses that provide circulating dexmedetomidine concentrations similar to those produced by medetomidine alone. ANIMALS: 8 healthy Beagles. PROCEDURES: Dogs received 3 IV treatments in a randomized crossover-design trial with a 2-week washout period between experiments (medetomidine [20 µg/kg], medetomidine [20 µg/kg] and vatinoxan [400 µg/kg], and medetomidine [40 µg/kg] and vatinoxan [800 µg/kg]; M20, M20V400, and M40V800, respectively). Sedation, visceral and somatic nociception, and plasma drug concentrations were assessed. Somatic and visceral nociception measurements and sedation scores were compared among treatments and over time. Sedation, visceral antinociception, and somatic antinociception effects of M20V400 and M40V800 were analyzed for noninferiority to effects of M20, and plasma drug concentration data were assessed for equivalence between treatments. RESULTS: Plasma dexmedetomidine concentrations after administration of M20 and M40V800 were equivalent. Sedation scores, visceral nociception measurements, and somatic nociception measurements did not differ significantly among treatments within time points. Overall sedative effects of M20V400 and M40V800 and visceral antinociceptive effects of M40V800 were noninferior to those produced by M20. Somatic antinociception effects of M20V400 at 10 minutes and M40V800 at 10 and 55 minutes after injection were noninferior to those produced by M20. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested coadministration with vatinoxan did not substantially diminish visceral antinociceptive effects of medetomidine when plasma dexmedetomidine concentrations were equivalent to those produced by medetomidine alone. For somatic antinociception, noninferiority of treatments was detected at some time points.


Assuntos
Medetomidina/farmacologia , Quinolizinas/farmacologia , Analgésicos/farmacologia , Animais , Estudos Cross-Over , Cães , Frequência Cardíaca/efeitos dos fármacos , Hipnóticos e Sedativos/farmacologia
14.
Am J Vet Res ; 81(5): 394-399, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32343179

RESUMO

OBJECTIVE: To compare the speed of onset and analgesic effect of mepivacaine deposited within or immediately outside the neurovascular bundle at the base of the proximal sesamoid bones in horses. ANIMALS: 6 horses with naturally occurring forefoot-related lameness. PROCEDURES: In a crossover study design, horses were randomly assigned to receive 1 of 2 treatments first, with the second treatment administered 3 to 7 days later. Trotting gait was analyzed with an inertial sensor-based motion analysis system immediately before treatment to determine degree of lameness. Afterward, ultrasound guidance was used to inject 2% mepivacaine hydrochloride around the palmar digital nerves of the affected forelimb at the level of the base of the proximal sesamoid bones either within the subcircumneural space or outside the circumneural sheath. After injection, gait was reevaluated at 5-minute intervals for 45 minutes. RESULTS: Mepivacaine deposition outside the circumneural sheath did not resolve lameness in any horse; for 3 horses, the mean time to 70% reduction of initial vertical head movement was 13.3 minutes, and the remaining 3 horses had no such reduction at any point. Mepivacaine deposition within the subcircumneural space resulted in a mean time to 70% reduction of initial vertical head movement of 6.7 minutes and mean time to resolution of lameness of 21.7 minutes. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that when peripheral nerves of horses lie within a sheath, local anesthetic solution should be deposited within the sheath for an effective nerve block. If local anesthetic solution is deposited outside the sheath, the nerve block may yield erroneous results.


Assuntos
Doenças dos Cavalos , Ossos Sesamoides , Analgésicos/farmacologia , Animais , Estudos Cross-Over , Membro Anterior , Marcha/efeitos dos fármacos , Cavalos , Coxeadura Animal , Mepivacaína/farmacologia
15.
BMC Complement Med Ther ; 20(1): 102, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32228549

RESUMO

BACKGROUND: Panch phoron is a mixture of five spices containing an equal proportion of Foeniculum vulgare (fennel), Trigonella foenum-graecum Linn (fenugreek), Nigella sativa (black cumin), Cuminum cyminum (cumin) and Brassica nigra (black mustard). The mixture is commonly used in Bangladeshi cuisine and possesses many pharmacological effects. In this study, we evaluated the antinociceptive and anti-inflammatory activities of aqueous panch phoron extract (PPE) in vivo, its possible mechanism of action and phytochemical analysis by High-Performance Liquid Chromatography (HPLC). We also investigated the effect of PPE on postoperative pain in mice. METHODS: HPLC was carried out using LC-20A Modular HPLC system to identify the bioactive compounds present in PPE. Five groups of Swiss albino male mice (n = 6 per group) were orally treated with 10 ml/kg of distilled water or 10 mg/kg of sodium diclofenac or three doses of PPE (100 mg/kg, 300 mg/kg, 500 mg/kg). In vivo assessment was carried out by the writhing test, tail-flick test, formalin test, and carrageenan induced paw edema test. The opioid antagonist, naloxone was used in the acetic acid test to evaluate the involvement of opioid receptors. To assess the effect of PPE in postoperative pain, mice that underwent sciatic nerve surgery were measured for the paw withdrawal latency in a hot water bath. RESULTS: In HPLC analysis, different types of phenolic compounds and flavonoids, including catechin hydrate, para-coumaric acid, vanillic acid, and syringic acid were detected. Treatment with PPE exhibited dose-dependent antinociceptive and anti-inflammatory activities in pain models (p < 0.05). Furthermore, naloxone did not reverse the effect of PPE in the writhing test. Mice that underwent sciatic nerve surgery showed that the paw withdrawal latency increased gradually over 7 days. CONCLUSIONS: Our results demonstrate that PPE has significant antinociceptive and anti-inflammatory activities and can provide significant postoperative analgesia.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Dor Pós-Operatória/tratamento farmacológico , Extratos Vegetais/farmacologia , Especiarias , Analgésicos/química , Animais , Anti-Inflamatórios/química , Bangladesh , Cromatografia Líquida de Alta Pressão , Masculino , Camundongos , Extratos Vegetais/química , Sementes/química
17.
PLoS One ; 15(3): e0230167, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32214334

RESUMO

Cannabis related online searches are associated with positive attitudes toward medical cannabis, particularly when information is obtained from dispensaries. Since pain is the main reason for medicinal cannabis use, information from dispensary websites has the potential to shape the attitude of pain patients towards cannabis. This is relevant because cannabis has demonstrated efficacy in neuropathic pain with low tetrahydrocannabinol (THC) concentrations (< 5-10%), in contrast to potent cannabis (>15% THC), which is highly rewarded in the recreational realm. The role of CBD in pain is not clear, however it has gained popularity. Thus, we hypothesize that the potency of medical cannabis that is advertised online is similar to the cannabis advertised for recreational purposes, which would potentially create a misconception towards medical cannabis. The current lack of knowledge surrounding advertised potencies in the legal cannabis market limits the ability to generate clear policies regarding online advertising to protect patients that are willing to use cannabis for their condition. Thus, we evaluated the advertised THC and CBD content of cannabis products offered online in dispensaries in the United States to determine products' suitability to medicinal use and compare the strength of products offered in legal medical and recreational programs. We recorded THC and CBD concentrations for all herb cannabis products provided by dispensary websites and compared them between or within states. Four Western states (CA, CO, NM, WA) and five Northeastern states (ME, MA, NH, RI, VT) were included. A total of 8,505 cannabis products across 653 dispensaries were sampled. Despite the clear differences between medicinal and recreational uses of cannabis, the average THC concentration advertised online in medicinal programs was similar (19.2% ±6.2) to recreational programs (21.5% ±6.0) when compared between states with different programs, or between medicinal and recreational programs within the same states (CO or WA). Lower CBD concentrations accompanied higher THC products. The majority of products, regardless of medicinal or recreational programs, were advertised to have >15% THC (70.3% - 91.4% of products). These stated concentrations seem unsuitable for medicinal purposes, particularly for patients with chronic neuropathic pain. Therefore, this information could induce the misconception that high potency cannabis is safe to treat pain. This data is consistent with reports in which THC and CBD in products from legal dispensaries or in nationwide products from the illegal market were actually measured, which indicates that patients consuming these products may be at risk of acute intoxication or long-term side effects. Our study offers grounds to develop policies that help prevent misconceptions toward cannabis and reduce risks in pain patients.


Assuntos
Drogas Ilícitas/farmacologia , Maconha Medicinal/farmacologia , Analgésicos/farmacologia , Cannabis , Dronabinol/farmacologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Humanos , Neuralgia/tratamento farmacológico , Estados Unidos
18.
J Pharmacol Exp Ther ; 373(3): 416-428, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32179573

RESUMO

Chronic pain is the most common reason reported for using medical cannabis. The goal of this research was to determine whether the two primary phytocannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), are effective treatments for persistent inflammatory pain. In experiment 1, inflammation was induced by intraplantar injection of Complete Freund's adjuvant (CFA). Then THC (0.0-4.0 mg/kg, i.p.) or CBD (0.0-10 mg/kg, i.p.) was administered twice daily for 3 days. On day 4, THC, CBD, or vehicle was administered, and allodynia, hyperalgesia, weight-bearing, locomotor activity, and hindpaw edema were assessed 0.5-4 hours postinjection. In experiment 2, CFA or mineral oil (no-pain control)-treated rats were given THC (2.0 mg/kg, i.p.), CBD (10 mg/kg, i.p.), or vehicle in the same manner as in experiment 1. Four hours postinjection on day 4, serum samples were taken for analysis of cytokines known to influence inflammatory pain: interleukin (IL)-1ß, IL-6, IL-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α THC dose-dependently reduced pain-related behaviors but did not reduce hindpaw edema, and little tolerance developed to THC's effects. In contrast, CBD effects on inflammatory pain were minimal. THC produced little to no change in serum cytokines, whereas CBD decreased IL-1ß, IL-10, and IFN-γ and increased IL-6. Few sex differences in antinociception or immune modulation were observed with either drug, but CFA-induced immune activation was significantly greater in males than females. These results suggest that THC may be more beneficial than CBD for reducing inflammatory pain in that THC maintains its efficacy with short-term treatment in both sexes and does not induce immune activation. SIGNIFICANCE STATEMENT: The pain-relieving effects of cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) are examined in male and female rats with persistent inflammatory pain to determine whether individual phytocannabinoids could be a viable treatment for men and women with chronic inflammatory pain. Additionally, sex differences in the immune response to an adjuvant and to THC and CBD are characterized to provide preliminary insight into immune-related effects of cannabinoid-based therapy for pain.


Assuntos
Analgésicos/farmacologia , Canabidiol/farmacologia , Canabinol/farmacologia , Dor Crônica/tratamento farmacológico , Dor Crônica/etiologia , Inflamação/complicações , Animais , Dor Crônica/metabolismo , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Tolerância a Medicamentos/fisiologia , Feminino , Inflamação/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Caracteres Sexuais
19.
BMC Complement Med Ther ; 20(1): 83, 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32171311

RESUMO

BACKGROUND: Recent studies pointed up that curcumin produces an anti-nociceptive effect in inflammatory and neuropathic pain. However, the possible mechanisms of action that underline the anti-allodynic effect induced by curcumin are not yet established. The purpose of this study was to determine the possible anti-allodynic effect of curcumin in rats with L5-L6 spinal nerve ligation (SNL). Furthermore, we study the possible participation of the NO-cyclic GMP-ATP-sensitive K+ channels pathway in the anti-allodynic effect induced by curcumin. METHODS: Tactile allodynia was measured using von Frey filaments by the up-down method in female Wistar rats subjected to SNL model of neuropathic pain. RESULTS: Intrathecal and oral administration of curcumin prevented, in a dose-dependent fashion, SNL-induced tactile allodynia. The anti-allodynic effect induced by curcumin was prevented by the intrathecal administration of L-NAME (100 µg/rat, a non-selective nitric oxide synthase inhibitor), ODQ (10 µg/rat, an inhibitor of guanylate-cyclase), and glibenclamide (50 µg/rat, channel blocker of ATP-sensitive K+ channels). CONCLUSIONS: These data suggest that the anti-allodynic effect induced by curcumin is mediated, at least in part, by the NO-cyclic GMP-ATP-sensitive K+ channels pathway in the SNL model of neuropathic pain in rats.


Assuntos
Analgésicos/farmacologia , Curcumina/farmacologia , GMP Cíclico/metabolismo , Hiperalgesia/tratamento farmacológico , Canais KATP/metabolismo , Óxido Nítrico/metabolismo , Animais , Feminino , Ratos , Ratos Wistar
20.
Psychopharmacology (Berl) ; 237(6): 1723-1735, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32162104

RESUMO

RATIONALE: Working memory deficits are present in schizophrenia (SZ) but remain insufficiently resolved by medications. Similar cognitive dysfunctions can be produced acutely in animals by elevating brain levels of kynurenic acid (KYNA). KYNA's effects may reflect interference with the function of both the α7 nicotinic acetylcholine receptor (α7nAChR) and the glycineB site of the NMDA receptor. OBJECTIVES: The aim of the present study was to examine, using pharmacological tools, the respective roles of these two receptor sites on performance in a delayed non-match-to-position working memory (WM) task (DNMTP). METHODS: DNMTP consisted of 120 trials/session (5, 10, and 15 s delays). Rats received two doses (25 or 100 mg/kg, i.p.) of L-kynurenine (KYN; bioprecursor of KYNA) or L-4-chlorokynurenine (4-Cl-KYN; bioprecursor of the selective glycineB site antagonist 7-Cl-kynurenic acid). Attenuation of KYN- or 4-Cl-KYN-induced deficits was assessed by co-administration of galantamine (GAL, 3 mg/kg) or PAM-2 (1 mg/kg), two positive modulators of α7nAChR function. Reversal of 4-Cl-KYN-induced deficits was examined using D-cycloserine (DCS; 30 mg/kg), a partial agonist at the glycineB site. RESULTS: Both KYN and 4-Cl-KYN administration produced dose-related deficits in DNMTP accuracy that were more severe at the longer delays. In KYN-treated rats, these deficits were reversed to control levels by GAL or PAM-2 but not by DCS. In contrast, DCS eliminated performance deficits in 4-Cl-KYN-treated animals. CONCLUSIONS: These experiments reveal that both α7nAChR and NMDAR activity are necessary for normal WM accuracy. They provide substantive new support for the therapeutic potential of positive modulators at these two receptor sites in SZ and other major brain diseases.


Assuntos
Encéfalo/metabolismo , Memória de Curto Prazo/fisiologia , Desempenho Psicomotor/fisiologia , Receptores de N-Metil-D-Aspartato/metabolismo , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Analgésicos/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Ácido Cinurênico/farmacologia , Cinurenina/farmacologia , Masculino , Memória de Curto Prazo/efeitos dos fármacos , Nicotina/farmacologia , Desempenho Psicomotor/efeitos dos fármacos , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/agonistas , Receptor Nicotínico de Acetilcolina alfa7/agonistas
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