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1.
Dtsch Arztebl Int ; 118(24): 423, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34369373
2.
Medicine (Baltimore) ; 100(33): e26767, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34414933

RESUMO

OBJECTIVE: The aim of this study was to investigate the effect of Ma Yinglong Shexiang Hemorrhoids Cream combined with pearl powder on pain and complications in patients with severe pressure ulcers. METHODS: One hundred seventeen patients with severe pressure ulcers hospitalized and treated in our hospital (January 2019--December 2019) were divided into Ma Yinglong Musk Hemorrhoid Cream Group (MY Group), Pearl Powder Group (PP Group), and combination with Ma Yinglong Musk Hemorrhoid Cream and Pearl Powder Group (MP group), 39 patients in each group. There was no significant difference in the general data of patients in MY group, PP group, and MP group. By analyzing the differences in clinical efficacy, secondary effects, scar incidence, pain, and clinical indicators of patients in the MY group, PP group, and MP group, the effects of Mayinglong Shexiang Hemorrhoid Cream combined with pearl powder in the treatment of pain and complications in patients with severe pressure ulcers were explored. RESULTS: After treatment, compared with the MY group and the PP group, the MP group had a higher clinical efficacy than the MY group and the PP group. Compared with MY group and PP group, the healing time, dressing change times, and dressing change time of MP group were better than MY group (P < .05). After treatment, the VAS score and incidence of secondary effects of the MP group was significantly lower than that of the MY group and PP group (P < .05). The incidence and area of scar formation in the MP group were lower than those in the MY group and the PP group (P < .05). CONCLUSION: Compared with Ma Yinglong Musk Hemorrhoid Cream or Pearl Powder, combination of Ma Yinglong Musk Hemorrhoid Cream and Pearl Powder are more effective in treating severe pressure ulcer patients, and can significantly reduce the pain in the affected area and reduce the occurrence of complications.


Assuntos
Medicina Tradicional Chinesa , Manejo da Dor/métodos , Dor/tratamento farmacológico , Dor/etiologia , Lesão por Pressão/complicações , Adulto , Feminino , Hemorroidas/tratamento farmacológico , Humanos , Masculino , Pomadas , Medição da Dor , Pós , Índice de Gravidade de Doença
3.
BMJ Open ; 11(8): e048652, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34380727

RESUMO

INTRODUCTION: Symptomatic treatments for osteoarthritis (OA) provide only small-to-moderate efficacy over placebo in randomised controlled trials (RCTs). Treatment guidelines therefore have emphasised the need to identify predictors of treatment response through subgroup and multiple regression analysis. Individual participant data (IPD) meta-analysis is recommended as an efficient approach for this purpose. To our knowledge, this has not been undertaken for oral non-steroidal anti-inflammatory drugs (NSAIDs), including paracetamol, in OA. In this IPD meta-analysis, we aim to identify RCTs with specific mechanistic features related to OA pain, such as joint inflammation. We hypothesise that NSAIDs may work better for participants with joint inflammation, whereas paracetamol may not. METHODS AND ANALYSIS: A comprehensive literature search will be conducted on the databases of Web of Science, Embase, Medline, CINAHL, AMED and the Cochrane Library from 1 January 1998 to 1 December 2020. All RCTs related to oral NSAIDs or paracetamol including placebo-controlled trials in people with OA that have evaluated pain-related peripheral risk factors (eg, clinically detected knee effusion, synovial hypertrophy or effusion on imaging, knee morning stiffness, elevated serum C-reactive protein (CRP) level) and/or central pain risk factors (eg, pain elsewhere, depression, anxiety, sleep disturbance) will be retrieved. The outcome will be change in pain from baseline. Change in function and patient global assessment will also be included as outcomes if available. Investigators of all eligible trials will be contacted for IPD. Multilevel regression models will be used to identify predictors for the specific (active-placebo) and the overall treatment effect (change from baseline in active group). ETHICS AND DISSEMINATION: No identifiable data will be included in this study and no formal ethics approval is required as no new data collection will be processed. Results of this hypothesis-driven IPD meta-analysis will be disseminated through conference presentations and publication in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42020165098.


Assuntos
Osteoartrite , Preparações Farmacêuticas , Acetaminofen/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Humanos , Metanálise como Assunto , Osteoartrite/tratamento farmacológico , Dor/tratamento farmacológico
4.
Int J Mol Sci ; 22(15)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34360719

RESUMO

Agonists of the Gi protein-coupled A3 adenosine receptor (A3AR) have shown important pain-relieving properties in preclinical settings of several pain models. Active as a monotherapy against chronic pain, A3AR agonists can also be used in combination with classic opioid analgesics. Their safe pharmacological profile, as shown by clinical trials for other pathologies, i.e., rheumatoid arthritis, psoriasis and fatty liver diseases, confers a realistic translational potential, thus encouraging research studies on the molecular mechanisms underpinning their antinociceptive actions. A number of pathways, involving central and peripheral mechanisms, have been proposed. Recent evidence showed that the prototypical A3AR agonist Cl-IB-MECA and the new, highly selective, A3AR agonist MRS5980 inhibit neuronal (N-type) voltage-dependent Ca2+ currents in dorsal root ganglia, a known pain-related mechanism. Other proposed pathways involve reduced cytokine production, immune cell-mediated responses, as well as reduced microglia and astrocyte activation in the spinal cord. The aim of this review is to summarize up-to-date information on A3AR in the context of pain, including cellular and molecular mechanisms underlying this effect. Based on their safety profile shown in clinical trials for other pathologies, A3AR agonists are proposed as novel, promising non-narcotic agents for pain control.


Assuntos
Agonistas do Receptor A3 de Adenosina/uso terapêutico , Sinalização do Cálcio/efeitos dos fármacos , Gânglios Espinais , Dor , Receptor A3 de Adenosina/metabolismo , Animais , Astrócitos/metabolismo , Gânglios Espinais/metabolismo , Gânglios Espinais/fisiopatologia , Humanos , Microglia/metabolismo , Dor/tratamento farmacológico , Dor/metabolismo , Dor/fisiopatologia
5.
BMC Psychiatry ; 21(1): 416, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34416868

RESUMO

BACKGROUND: In light of the ongoing opioid overdose crisis, there is an urgent need for research on the impacts of mental health among people presenting with concurrent pain and substance use. This study examined the effect of depressive symptoms on pain severity and functional interference among people who use drugs (PWUD) during a community-wide overdose crisis. METHODS: From December 1st 2016 to December 31st 2018, 288 participants in two cohort studies of PWUD in Vancouver, Canada completed interviewer-administered questionnaires that included the Brief Pain Inventory and PROMIS Emotional Distress-Depression instruments. Generalized linear regression modelling (GLM) was used to examine the cross-sectional effect of depressive symptoms and other confounding factors on pain severity and interference. RESULTS: Moderate to severe depressive symptoms were significantly associated with greater pain-related functional interference (adjusted ß = 1.24, 95% confidence interval [CI] = 0.33-2.15), but not significantly associated with greater average pain severity (adjusted ß = 0.22, 95% CI = - 0.3 - 0.82), when controlling for confounding variables. Reported daily heroin use (adjusted ß = 1.26, 95% CI = 0.47-2.05) and non-fatal overdose (adjusted ß = 1.02, 95% CI = 0.08-1.96) were also significantly associated with greater pain-related functional interference. CONCLUSIONS: In a substance-using population, greater pain-related functional interference was positively associated with depressive symptoms as well as overdose and daily heroin use. These findings emphasize the need to address the functional impact of pain, mental health comorbidity, and high-risk substance use that may contribute to overdose and other harms.


Assuntos
Depressão , Overdose de Drogas , Estudos de Coortes , Estudos Transversais , Depressão/complicações , Depressão/epidemiologia , Humanos , Dor/complicações , Dor/tratamento farmacológico , Dor/epidemiologia
6.
J Opioid Manag ; 17(3): 207-214, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34259332

RESUMO

A growing number of individuals live with an opioid use disorder (OUD). While many go on to recover from such disorders, certainly, there will be individuals in palliative care (PC) at some point who still suffer with OUD. One of the major barriers to PC for individuals recovering and currently suffering from an OUD is the stigma related to having an OUD. Therefore, in the context of PC, it is important to understand the relationship that exists between PC, OUDs, and how stereo-types related to substance use disorders affect patient engagement in PC. For this paper, the focus will be on how stereotypes affect pain management in PC for persons with an OUD. A review of current literature regarding OUDs and pain management indicates a need for care specific to the needs of those in PC who formerly and/or currently suffer from an OUD in order to avoid relapse or worsening of their affliction while still managing their pain. The striking lack of knowledge and resources regarding OUDs and their treatment indicates a need to strengthen/increase resources for physicians to educate on treating OUDs as well as alternatives for pain management. This article presents dignity-enhancing care as a gateway to fairly treat individuals with an OUD and to get rid of the stigma associated with OUD patients.


Assuntos
Manejo da Dor , Cuidados Paliativos , Analgésicos Opioides/uso terapêutico , Análise Ética , Humanos , Dor/diagnóstico , Dor/tratamento farmacológico
7.
RMD Open ; 7(2)2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34226183

RESUMO

BACKGROUND: Pain is a core domain of psoriatic arthritis (PsA). This post hoc analysis evaluated time to pain improvement and the impact of baseline pain severity on pain response in patients with PsA receiving tofacitinib. METHODS: Data from two trials (NCT01877668; NCT01882439) in patients receiving tofacitinib 5 mg twice daily, placebo switching to tofacitinib 5 mg twice daily at month 3 (placebo-to-tofacitinib) or adalimumab (NCT01877668 only) were included. Improvement in pain (≥30%/≥50% decrease from baseline in Visual Analogue Scale pain score) was assessed; median time to initial (first post-baseline visit)/continued (first two consecutive post-baseline visits) pain improvement was estimated (Kaplan-Meier) for all treatment arms. A parametric model was used to determine the relationship between baseline pain severity and time to pain response in patients receiving tofacitinib. RESULTS: At month 3, more patients experienced pain improvements with tofacitinib/adalimumab versus placebo. Median days (95% CI) to initial/continued pain improvements of ≥30% and ≥50%, respectively, were 55 (29-57)/60 (57-85) and 85 (57-92)/171 (90-not estimable (NE)) for tofacitinib, versus 106 (64-115)/126 (113-173) and 169 (120-189)/NE (247-NE) for placebo-to-tofacitinib. Pain improvements were also experienced more quickly for adalimumab versus placebo. Predicted time to ≥30%/≥50% pain improvement was shorter in patients with higher baseline pain versus lower baseline pain (tofacitinib arm only). CONCLUSIONS: In patients with PsA, pain improvements were experienced by more patients, and more rapidly, with tofacitinib and adalimumab versus placebo. In those receiving tofacitinib, higher baseline pain was associated with faster pain improvements.


Assuntos
Antirreumáticos , Artrite Psoriásica , Antirreumáticos/uso terapêutico , Artrite Psoriásica/complicações , Artrite Psoriásica/tratamento farmacológico , Humanos , Dor/tratamento farmacológico , Dor/etiologia , Piperidinas , Pirimidinas , Resultado do Tratamento
8.
Dermatol Surg ; 47(3): 373-376, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34328289

RESUMO

BACKGROUND: Chondrodermatitis nodularis helicis (CNH) is a common chronic condition characterized by a tender nodule on the helix or antihelix of the ear which may or may not have accompanying crusting, scaling, or ulceration and that is often difficult to treat. OBJECTIVE: Develop an easy, effective, and durable treatment to reduce the pain and clinical signs including ulcerations associated with CNH using injectable hyaluronic acid (HA). MATERIALS AND METHODS: Twenty-four patients were injected and followed up in 2 to 4 weeks intervals using 0.2 to 0.3 mL of various HA with a high G-Prime. RESULTS: Injectable HA significantly improved the symptoms and also the clinical appearance of all patients treated after 1 or 2 injections except 1 patient. Extrusion of the material through a preexisting ulcer usually required a second follow-up injection 2 weeks later. No adverse events were noted with the injections other than the intentional visible bulging of the injected region with HA. CONCLUSION: Injectable HA provides almost immediate relief from the discomfort of CNH in most cases in less than 1 or 2 weeks, significantly improves the clinical appearance over time and resolves accompanying ulcerations.


Assuntos
Doenças das Cartilagens/tratamento farmacológico , Dermatite/tratamento farmacológico , Otopatias/tratamento farmacológico , Ácido Hialurônico/administração & dosagem , Dor/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Adjuvantes Imunológicos/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças das Cartilagens/complicações , Doenças das Cartilagens/diagnóstico , Doença Crônica , Dermatite/complicações , Dermatite/diagnóstico , Pavilhão Auricular , Otopatias/complicações , Otopatias/diagnóstico , Feminino , Seguimentos , Humanos , Injeções Intralesionais , Masculino , Pessoa de Meia-Idade , Dor/etiologia
9.
Agri ; 33(3): 203-204, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34318916

RESUMO

Pain is a common but often ignored symptom in COVID-19 patients. Early and adequate treatment with detailed pain assessment in these patients may reduce the risk of pain chronicization, and mood dysregulation. To provide analgesia, paracetamol can be listed as the first option in these patients, and then NSAIDs can also be reliably used for pain management in patients with COVID-19 if there are no absolute contraindications such as kidney failure or gastric bleeding. Codeine is also a good alternative for patients with anxiety who do not respond to simple pain-relievers.


Assuntos
Analgésicos não Narcóticos/uso terapêutico , COVID-19/complicações , Dor/etiologia , SARS-CoV-2 , Acetaminofen/administração & dosagem , Acetaminofen/uso terapêutico , Administração Oral , Analgésicos não Narcóticos/administração & dosagem , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/uso terapêutico , Humanos , Dor/tratamento farmacológico
10.
Int J Mol Sci ; 22(14)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34298954

RESUMO

Opioids are regarded as among the most effective analgesic drugs and their use for the management of pain is considered standard of care. Despite their systematic administration in the peri-operative period, their impact on tissue repair has been studied mainly in the context of scar healing and is only beginning to be documented in the context of true tissue regeneration. Indeed, in mammals, growing evidence shows that opioids direct tissue repair towards scar healing, with a loss of tissue function, instead of the regenerative process that allows for recovery of both the morphology and function of tissue. Here, we review recent studies that highlight how opioids may prevent a regenerative process by silencing nociceptive nerve activity and a powerful anti-inflammatory effect. These data open up new perspectives for inducing tissue regeneration and argue for opioid-restricted strategies for managing pain associated with tissue injury.


Assuntos
Analgésicos Opioides/uso terapêutico , Manejo da Dor , Dor/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Animais , Humanos , Dor/metabolismo , Dor/patologia
11.
Int J Mol Sci ; 22(12)2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34203675

RESUMO

Recently, we found that the deletion of TRPC5 leads to increased inflammation and pain-related behaviour in two animal models of arthritis. (-)-Englerin A (EA), an extract from the East African plant Phyllanthus engleri has been identified as a TRPC4/5 agonist. Here, we studied whether or not EA has any anti-inflammatory and analgesic properties via TRPC4/5 in the carrageenan model of inflammation. We found that EA treatment in CD1 mice inhibited thermal hyperalgesia and mechanical allodynia in a dose-dependent manner. Furthermore, EA significantly reduced the volume of carrageenan-induced paw oedema and the mass of the treated paws. Additionally, in dorsal root ganglion (DRG) neurons cultured from WT 129S1/SvIm mice, EA induced a dose-dependent cobalt uptake that was surprisingly preserved in cultured DRG neurons from 129S1/SvIm TRPC5 KO mice. Likewise, EA-induced anti-inflammatory and analgesic effects were preserved in the carrageenan model in animals lacking TRPC5 expression or in mice treated with TRPC4/5 antagonist ML204.This study demonstrates that while EA activates a sub-population of DRG neurons, it induces a novel TRPC4/5-independent analgesic and anti-inflammatory effect in vivo. Future studies are needed to elucidate the molecular and cellular mechanisms underlying EA's anti-inflammatory and analgesic effects.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Sesquiterpenos de Guaiano/farmacologia , Canais de Cátion TRPC/metabolismo , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Carragenina , Células Cultivadas , Cobalto/metabolismo , Modelos Animais de Doenças , Edema/patologia , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Hiperalgesia/tratamento farmacológico , Inflamação/complicações , Inflamação/tratamento farmacológico , Inflamação/patologia , Masculino , Camundongos Knockout , Dor/complicações , Dor/tratamento farmacológico , Dor/patologia , Fenótipo , Células Receptoras Sensoriais/efeitos dos fármacos , Células Receptoras Sensoriais/metabolismo , Sesquiterpenos de Guaiano/uso terapêutico
12.
Molecules ; 26(11)2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34199486

RESUMO

In this study, we aimed to design and synthesize novel molecules carrying both the thiazole and piperazine rings in their structures and to investigate their antinociceptive activity. Targeted compounds were obtained by reacting thiosemicarbazide derivative and appropriate 2-bromoacetophenone in ethanol. The structures of the obtained compounds were determined using data from various spectroscopic methods (IR, 1H-NMR, 13C-NMR, and LCMSMS). Experimental data from in vivo tests showed that test compounds 3a-3c, 3f, and 3g (50 mg/kg) significantly prolonged reaction times of animals in tail-clip and hot-plate tests compared to the controls, indicating that these compounds possess centrally mediated antinociceptive activities. Furthermore, these compounds reduced the number of writhing behaviors in the acetic acid-induced writhing tests, showing that the compounds also possess peripheral antinociceptive activity. In the mechanistic studies, naloxone pre-treatments abolished the antinociceptive activities of compounds 3a-3c, 3f, and 3g, indicating that opioidergic mechanisms were involved in their antinociceptive effects. Molecular docking studies demonstrating significant interactions between the active compounds and µ- and δ-opioid receptor proteins supported the pharmacological findings. This study is the first showing that molecules designed to bear thiazole and piperazine moieties together on their structure exert centrally and peripherally mediated antinociceptive effects by activating the opioid system.


Assuntos
Acetofenonas/química , Analgésicos/administração & dosagem , Analgésicos/síntese química , Dor/tratamento farmacológico , Receptores Opioides/metabolismo , Semicarbazidas/química , Analgésicos/química , Analgésicos/farmacologia , Animais , Modelos Animais de Doenças , Masculino , Camundongos , Modelos Moleculares , Simulação de Acoplamento Molecular , Estrutura Molecular , Naloxona/administração & dosagem , Naloxona/farmacologia , Dor/metabolismo , Conformação Proteica , Receptores Opioides/química , Receptores Opioides delta/química , Receptores Opioides delta/metabolismo , Receptores Opioides mu/química , Receptores Opioides mu/metabolismo
13.
Int J Mol Sci ; 22(14)2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34298911

RESUMO

Osteoarthritis (OA) is the most common articular degenerative disease characterized by chronic pain, joint inflammation, and movement limitations, which are significantly influenced by aberrant epigenetic modifications of numerous OA-susceptible genes. Recent studies revealed that both the abnormal activation and differential expression of histone deacetylases (HDACs) might contribute to OA pathogenesis. In this study, we investigated the chondroprotective effects of a marine-derived HDAC inhibitor, panobinostat, on anterior cruciate ligament transection (ACLT)-induced experimental OA rats. The intra-articular administration of 2 or 10 µg of panobinostat (each group, n = 7) per week from the 6th to 17th week attenuates ACLT-induced nociceptive behaviors, including secondary mechanical allodynia and weight-bearing distribution. Histopathological and microcomputed tomography analysis showed that panobinostat significantly prevents cartilage degeneration after ACLT. Moreover, intra-articular panobinostat exerts hypertrophic effects in the chondrocytes of articular cartilage by regulating the protein expressions of HDAC4, HDAC6, HDAC7, runt-domain transcription factor-2, and matrix metalloproteinase-13. The study indicated that HDACs might have different modulations on the chondrocyte phenotype in the early stages of OA development. These results provide new evidence that panobinostat may be a potential therapeutic drug for OA.


Assuntos
Ligamento Cruzado Anterior/efeitos dos fármacos , Cartilagem Articular/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Osteoartrite do Joelho/tratamento farmacológico , Dor/tratamento farmacológico , Panobinostat/farmacologia , Animais , Ligamento Cruzado Anterior/metabolismo , Lesões do Ligamento Cruzado Anterior/tratamento farmacológico , Lesões do Ligamento Cruzado Anterior/metabolismo , Doenças das Cartilagens/tratamento farmacológico , Doenças das Cartilagens/metabolismo , Cartilagem Articular/metabolismo , Condrócitos/metabolismo , Modelos Animais de Doenças , Masculino , Osteoartrite do Joelho/metabolismo , Dor/metabolismo , Ratos , Ratos Wistar , Suporte de Carga
14.
Nurs Res ; 70(4): 273-280, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34160183

RESUMO

BACKGROUND: Clinicians may place more weight on vocal complaints of pain than the other pain behaviors when making decisions about pain management. OBJECTIVES: We examined the association between documented pain behaviors and pharmacological pain management among nursing home residents. METHODS: We included 447,684 residents unable to self-report pain, with staff-documented pain behaviors (vocal, nonverbal, facial expressions, protective behaviors) and pharmacological pain management documented on the 2010-2016 Minimum Data Set 3.0. The outcome was no pharmacological pain medications, as needed only (pro re nata [PRN]), as scheduled only, or as scheduled with PRN medications. We estimated adjusted odds ratios and 95% confidence intervals from multinomial logistic models. RESULTS: Relative to residents with vocal complaints only, those with one pain behavior documented (i.e., nonverbal, facial, or protective behavior) were more likely to lack pain medication versus scheduled and PRN medications. Residents with multiple pain behaviors documented were least likely to have no treatment relative to scheduled with PRN medications, PRN only, or scheduled only pain medication regimens. DISCUSSION: The type and number of pain behaviors observed are associated with pharmacological pain management regimen. Improving staff recognition of pain among residents unable to self-report is warranted in nursing homes.


Assuntos
Sintomas Comportamentais/psicologia , Casas de Saúde , Manejo da Dor , Dor , Preparações Farmacêuticas/administração & dosagem , Idoso , Feminino , Humanos , Masculino , Dor/tratamento farmacológico , Dor/psicologia
15.
J Palliat Med ; 24(7): 1100-1101, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34128705
17.
Toxins (Basel) ; 13(5)2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-34067828

RESUMO

The primary studies have shown that scorpion analgesic peptide N58A has a significant effect on voltage-gated sodium channels (VGSCs) and plays an important role in neuropathic pain. The purpose of this study was to investigate the analgesic effect of N58A on trigeminal neuralgia (TN) and its possible mechanism. The results showed that N58A could significantly increase the threshold of mechanical pain and thermal pain and inhibit the spontaneous asymmetric scratching behavior of rats. Western blotting results showed that N58A could significantly reduce the protein phosphorylation level of ERK1/2, P38, JNK, and ERK5/CREB pathways and the expression of Nav1.8 and Nav1.9 proteins in a dose-dependent manner. The changes in current and kinetic characteristics of Nav1.8 and Nav1.9 channels in TG neurons were detected by the whole-cell patch clamp technique. The results showed that N58A significantly decreased the current density of Nav1.8 and Nav1.9 in model rats, and shifted the activation curve to hyperpolarization and the inactivation curve to depolarization. In conclusion, the analgesic effect of N58A on the chronic constriction injury of the infraorbital (IoN-CCI) model rats may be closely related to the regulation of the MAPK pathway and Nav1.8 and Nav1.9 sodium channels.


Assuntos
Analgésicos/farmacologia , Peptídeos/farmacologia , Venenos de Escorpião/química , Neuralgia do Trigêmeo/tratamento farmacológico , Analgésicos/administração & dosagem , Analgésicos/isolamento & purificação , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Canal de Sódio Disparado por Voltagem NAV1.8/efeitos dos fármacos , Canal de Sódio Disparado por Voltagem NAV1.8/metabolismo , Canal de Sódio Disparado por Voltagem NAV1.9/efeitos dos fármacos , Canal de Sódio Disparado por Voltagem NAV1.9/metabolismo , Dor/tratamento farmacológico , Técnicas de Patch-Clamp , Peptídeos/administração & dosagem , Peptídeos/isolamento & purificação , Ratos , Ratos Sprague-Dawley , Escorpiões , Tetrodotoxina/farmacologia
19.
Pain ; 162(Suppl 1): S117-S124, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34138827

RESUMO

ABSTRACT: The President of the International Association for the Study of Pain established a task force on cannabis and cannabinoid analgesia to systematically examine the evidence on (1) analgesic pharmacology of cannabinoids and preclinical evidence on their efficacy in animal models of injury-related or pathological persistent pain; (2) the clinical efficacy of cannabis, cannabinoids, and cannabis-based medicines for pain; (3) harms related to long-term use of cannabinoids; as well as (4) societal issues and policy implications related to the use of these compounds for pain management. Here, we summarize key knowledge gaps identified in the task force outputs and propose a research agenda for generating high-quality evidence on the topic. The systematic assessment of preclinical and clinical literature identified gaps in rigor of study design and reporting across the translational spectrum. We provide recommendations to improve the quality, rigor, transparency, and reproducibility of preclinical and clinical research on cannabis and cannabinoids for pain, as well as for the conduct of systematic reviews on the topic. Gaps related to comprehensive understanding of the endocannabinoid system and cannabinoid pharmacology, including pharmacokinetics and drug formulation aspects, are discussed. We outline key areas where high-quality clinical trials with cannabinoids are needed. Remaining important questions about long-term and short-term safety of cannabis and cannabinoids are emphasized. Finally, regulatory, societal, and policy challenges associated with medicinal and nonmedicinal use of cannabis are highlighted, with recommendations for improving patient safety and reducing societal harms in the context of pain management.


Assuntos
Analgesia , Canabinoides , Cannabis , Analgésicos/uso terapêutico , Animais , Canabinoides/uso terapêutico , Humanos , Dor/tratamento farmacológico , Manejo da Dor , Reprodutibilidade dos Testes , Revisões Sistemáticas como Assunto
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