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1.
Curr Pain Headache Rep ; 28(5): 335-372, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38472618

RESUMO

PURPOSE OF REVIEW: To evaluate the effectiveness of radiofrequency neurotomy in managing sacroiliac joint pain utilizing a systematic review with meta-analysis of randomized controlled trials (RCTs) and observational studies. RECENT FINDINGS: The prevalence of sacroiliac joint pain is estimated at around 25% of low back pain cases, and its diagnosis lacks a gold standard. Treatments include exercise therapy, injections, ablation, and fusion, with variable effectiveness. COVID-19 altered utilization patterns of interventions, including sacroiliac joint procedures, and the evidence for these interventions remains inconclusive. Recently, Medicare has issued its local coverage determinations (LCDs) in the United States, which provides noncoverage of sacroiliac joint radiofrequency neurotomy. Additionally, a recent systematic review of sacroiliac joint injections showed Level III or fair evidence. The sacroiliac joint, a critical axial joint linking the spine and pelvis, contributes to low back pain. Its complex innervation pattern varies among individuals. Sacroiliac joint dysfunction, causing pain and stiffness, arises from diverse factors.The present systematic review and meta-analysis aimed to evaluate radiofrequency neurotomy's effectiveness for sacroiliac joint pain management by applying rigorous methodology, considering both RCTs and observational studies. Despite methodological disparities, the evidence from this review, supported by changes in pain scores and functional improvement, suggests Level III evidence with fair recommendation for radiofrequency neurotomy as a treatment option. The review's strengths include its comprehensive approach and quality assessment. However, limitations persist, including variations in criteria and technical factors, underscoring the need for further high-quality studies in real-world scenarios.


Assuntos
Dor Lombar , Ablação por Radiofrequência , Articulação Sacroilíaca , Articulação Sacroilíaca/cirurgia , Humanos , Dor Lombar/cirurgia , Dor Lombar/terapia , Ablação por Radiofrequência/métodos , Resultado do Tratamento , COVID-19 , Ensaios Clínicos Controlados Aleatórios como Assunto , Denervação/métodos
2.
Int J Mol Sci ; 25(11)2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38892091

RESUMO

Substance P (SP) plays a crucial role in pain modulation, with significant implications for major depressive disorder (MDD), anxiety disorders, and post-traumatic stress disorder (PTSD). Elevated SP levels are linked to heightened pain sensitivity and various psychiatric conditions, spurring interest in potential therapeutic interventions. In chronic pain, commonly associated with MDD and anxiety disorders, SP emerges as a key mediator in pain and emotional regulation. This review examines SP's impact on pain perception and its contributions to MDD, anxiety disorders, and PTSD. The association of SP with increased pain sensitivity and chronic pain conditions underscores its importance in pain modulation. Additionally, SP influences the pathophysiology of MDD, anxiety disorders, and PTSD, highlighting its potential as a therapeutic target. Understanding SP's diverse effects provides valuable insights into the mechanisms underlying these psychiatric disorders and their treatment. Further research is essential to explore SP modulation in psychiatric disorders and develop more effective treatment strategies.


Assuntos
Dor Crônica , Transtorno Depressivo Maior , Transtornos de Estresse Pós-Traumáticos , Substância P , Humanos , Dor Crônica/psicologia , Substância P/metabolismo , Transtorno Depressivo Maior/metabolismo , Transtorno Depressivo Maior/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/metabolismo , Transtornos de Ansiedade , Animais , Transtornos Mentais/metabolismo
3.
Int J Mol Sci ; 24(3)2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36768188

RESUMO

Millions of people are affected by pain-related conditions worldwide. Literature has consistently shown that each individual experiences and perceives pain in a unique manner due to biological, environmental, and cultural factors in which they have been raised. It has been established that biological males and females perceive pain differently and that it may be partially explained by their distinct hormonal profiles since birth, which are only further magnified during puberty. For biological males, high levels of testosterone have shown to increase their pain threshold; and for biological females, estrogen fluctuations have shown to increase pain intensity and perception. However, sex hormones have not been studied in the context of pain treatment or their impact on biochemical pathways involved in pain perception. For this purpose, the transgender community serves as a unique population to investigate the impact of hormone replacement therapy on molecular pathways involved in the perception of pain. The purpose of this review is to explore the biochemistry of hormone replacement in transgender patients who also have other pain-related conditions such as headaches, fibromyalgia, temporomandibular myalgia, and visceral pain.


Assuntos
Pessoas Transgênero , Dor Visceral , Masculino , Feminino , Humanos , Hormônios Esteroides Gonadais , Testosterona , Limiar da Dor , Hormônios
4.
Pain Pract ; 23(1): 94-109, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35869813

RESUMO

BACKGROUND: Chronobiology is the science of how physiological processes in the body follow a pattern of time. Pain has been shown to follow a circadian rhythm, with different types of pain having variable expression along this rhythm. OBJECTIVE: This article reviews the nature of diurnal variations in pain along with a discussion of the mechanisms of circadian rhythm of pain. EVIDENCE REVIEW: We conducted a literature search on the PubMed and Google Scholar electronic databases, through April 2022. Publications were screened for English language, full-text availability, and human subjects. Randomized controlled trials and observational trials were included. Data were extracted from studies on patients with acute or chronic pain phenotypes, which provide pain severity data and corresponding diurnal time points. FINDINGS: The literature search led to the inclusion of 39 studies. A circadian pattern of pain was found to be present in nociceptive, neuropathic, central, and mixed pain states. Postoperative pain, fibromyalgia, trigeminal neuralgia, and migraines were associated with higher pain scores in the morning. Temporomandibular joint pain, neuropathic pain, labor pain, biliary colic, and cluster headaches increased throughout the day to reach a peak in the evening or night. Arthritis and cancer pain were not associated with any circadian rhythmicity. Furthermore, the circadian rhythm of pain was not found to be altered in patients on analgesics. CONCLUSION: The results of this review suggest that an understanding of diurnal variation may help improve therapeutic strategies in pain management, for instance through analgesic titration.


Assuntos
Dor Crônica , Fibromialgia , Neuralgia , Neuralgia do Trigêmeo , Gravidez , Feminino , Humanos , Analgésicos/uso terapêutico , Dor Crônica/tratamento farmacológico , Fibromialgia/tratamento farmacológico , Neuralgia/tratamento farmacológico , Neuralgia do Trigêmeo/tratamento farmacológico
5.
Lancet ; 398(10294): 78-92, 2021 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-34115979

RESUMO

Low back pain covers a spectrum of different types of pain (eg, nociceptive, neuropathic and nociplastic, or non-specific) that frequently overlap. The elements comprising the lumbar spine (eg, soft tissue, vertebrae, zygapophyseal and sacroiliac joints, intervertebral discs, and neurovascular structures) are prone to different stressors, and each of these, alone or in combination, can contribute to low back pain. Due to numerous factors related to low back pain, and the low specificity of imaging and diagnostic injections, diagnostic methods for this condition continue to be a subject of controversy. The biopsychosocial model posits low back pain to be a dynamic interaction between social, psychological, and biological factors that can both predispose to and result from injury, and should be considered when devising interdisciplinary treatment plans. Prevention of low back pain is recognised as a pivotal challenge in high-risk populations to help tackle high health-care costs related to therapy and rehabilitation. To a large extent, therapy depends on pain classification, and usually starts with self-care and pharmacotherapy in combination with non-pharmacological methods, such as physical therapies and psychological treatments in appropriate patients. For refractory low back pain, a wide range of non-surgical (eg, epidural steroid injections and spinal cord stimulation for neuropathic pain, and radiofrequency ablation and intra-articular steroid injections for mechanical pain) and surgical (eg, decompression for neuropathic pain, disc replacement, and fusion for mechanical causes) treatment options are available in carefully selected patients. Most treatment options address only single, solitary causes and given the complex nature of low back pain, a multimodal interdisciplinary approach is necessary. Although globally recognised as an important health and socioeconomic challenge with an expected increase in prevalence, low back pain continues to have tremendous potential for improvement in both diagnostic and therapeutic aspects. Future research on low back pain should focus on improving the accuracy and objectivity of diagnostic assessments, and devising treatment algorithms that consider unique biological, psychological, and social factors. High-quality comparative-effectiveness and randomised controlled trials with longer follow-up periods that aim to establish the efficacy and cost-effectiveness of low back pain management are warranted.


Assuntos
Dor Lombar , Humanos , Dor Lombar/diagnóstico , Dor Lombar/fisiopatologia , Dor Lombar/terapia , Fatores de Risco
6.
Pain Med ; 22(8): 1760-1766, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-33502505

RESUMO

OBJECTIVE: We compared the reduction in pain and opioid consumption in patients with chronic spinal pain on concomitant gabapentinoids and opioids with patients using opioids only. DESIGN: This was a retrospective chart review of patients with chronic neck or low back pain who were on opioids with at least a 24-month follow-up. SETTING: Single-center pain clinic in an urban setting. SUBJECTS: 167 patients with chronic spinal pain lasting at least six months. METHODS: Patients on gabapentin or pregabalin were included in the gabapentinoid group, while the other patients were included in the non-gabapentinoid group. Primary outcome was assessment of pain scores measured via a numeric rating scale (NRS), and secondary outcomes were response to the treatment (>2 point reduction on NRS) and daily opioid use measured in morphine milliequivalents. RESULTS: Pain scores were reduced in the first six months and plateaued after that in both groups. At the end of 24 months, the average pain score was 6.71 in the gabapentinoid group, while the average pain score was 7.18 in the non-gabapentinoid group. There was no statistical significance between the groups (p = 0.28). There was no difference in response to treatment in gabapentinoid group (33.3%) when compared with non-gabapentinoid group (32.7%). We also failed to find any significant difference in daily opioid usage between the two groups. CONCLUSION: Gabapentinoids may not lead to reduction in pain or opioid consumption in patients with chronic spinal pain. A careful approach must be adopted while prescribing gabapentinoids in the chronic spinal pain patient population.


Assuntos
Analgésicos Opioides , Dor Lombar , Analgésicos Opioides/uso terapêutico , Gabapentina/uso terapêutico , Humanos , Dor Lombar/tratamento farmacológico , Pregabalina , Estudos Retrospectivos
7.
Anesth Analg ; 130(4): 917-924, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31206434

RESUMO

BACKGROUND: Pulmonary complications after total joint arthroplasty (TJA) are uncommon but have significant cost impact. Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are 2 of the 5 top procedures requiring inpatient stay within the United States. Subsequent pulmonary complications therefore may impose substantial cost burden for US health care. The purpose of this study was to describe the incidence, risk factors, and clinical implications of pulmonary complications (ie, pneumonia, respiratory failure, pulmonary embolism [PE], and aspiration) after TJA in the United States. METHODS: The National Inpatient Sample (NIS) was queried for all patients undergoing primary, elective THA and TKA between years 2004 and 2014. Pulmonary complications were defined as the occurrence of pneumonia, respiratory failure, PE, or aspiration after TJA. Demographic and clinical characteristics, inpatient cost, length of stay (LOS), and mortality were compared between patients with and without documented perioperative pulmonary complications. Given the stratified nature of the NIS database, estimates of incidence throughout the United States were made with application of trend weights to observed database frequencies. Analyses of estimated annual complication rates were made using χ tests. RESULTS: Between 2004 and 2014, an estimated 2,679,351 patients underwent elective primary THA. A total of 5,527,205 patients were estimated to have undergone elective primary TKA. THA 1.42% (95% CI, 1.37%-1.47%) and 1.71% (95% CI, 1.66%-1.76%) of TKA procedures were complicated by pneumonia, respiratory failure, PE, or aspiration. During this time, the incidence of perioperative pulmonary complications decreased from 1.57% (95% CI, 1.41%-1.73%) to 1.01% (95% CI, 0.92%-1.10%) after THA (P < .0001) and from 2.03% (95% CI, 1.88%-2.18%) to 1.33% (95% CI, 1.25%-1.42%) after TKA (P < .0001). The adjusted odds ratio (aOR) of experiencing a pulmonary complication was highest among patients with history of significant weight loss (aOR = 4.77; 99.9% CI, 3.97-5.73), fluid/electrolyte disorders (aOR = 3.33; 99.9% CI, 3.11-3.56), congestive heart failure (CHF; aOR = 3.32; 99.9% CI, 3.07-3.58), preexisting paralytic condition (aOR = 2.03; 99.9% CI, 1.57-2.61), and human immunodeficiency virus infection (aOR = 2.00; 99.9% CI, 1.06-3.78). Perioperative pulmonary complications were associated with increased LOS (THA = 3.03 days; 99.9% CI, 2.76-3.31; TKA = +2.72 days; 99.9% CI, 2.58-2.86), increased hospital costs (THA = +9163 US dollars; 99.9% CI, 8054-10,272; TKA = +7257 US dollars; 99.9% CI, 6650-7865), and increased mortality (THA: aOR = 121; 99.9% CI, 78-187; TKA: aOR = 150; 95% CI, 97-233). CONCLUSIONS: Despite a decline in overall incidence, perioperative pulmonary complications represent a significant potential source of perioperative morbidity and mortality. The current study highlights potential risk factors for pulmonary complications. Recognition of these factors may help to better stratify patients and mitigate risk of potential complications. This is particularly true of respiratory failure as it is associated with the high increases in resource utilization and mortality in this group.


Assuntos
Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Pneumopatias/etiologia , Complicações Pós-Operatórias/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril/economia , Artroplastia de Quadril/mortalidade , Artroplastia do Joelho/economia , Artroplastia do Joelho/mortalidade , Procedimentos Cirúrgicos Eletivos , Feminino , Custos Hospitalares , Humanos , Incidência , Tempo de Internação , Pneumopatias/mortalidade , Masculino , Pessoa de Meia-Idade , Pneumonia/epidemiologia , Pneumonia/etiologia , Pneumonia Aspirativa/epidemiologia , Pneumonia Aspirativa/etiologia , Complicações Pós-Operatórias/mortalidade , Insuficiência Respiratória/epidemiologia , Insuficiência Respiratória/etiologia , Fatores de Risco , Resultado do Tratamento , Estados Unidos/epidemiologia
8.
Neurol Sci ; 41(10): 2703-2710, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32367326

RESUMO

The US government and other key stakeholders including professional medical bodies have amended recommendations in recent years to emphasize using no opioids or the lowest effective dose of opioids needed for treatment of chronic pain. However, there remains an unmet need for pain treatments that can both relieve the pain of patients and reduce the doses of opioids they require. The Center for Medicare and Medicaid Services (CMS) is currently considering such treatments through the SUPPORT ACT and has recently conferred with the Health and Human Services (HHS) Inter-agency Pain Management Task Force to consider such therapies. We reviewed literature evidence in PubMed on pain relief and opioid reduction following spinal cord stimulation (SCS) treatment. SCS presents an effective non-pharmacologic pain treatment modality that has been used for decades to reduce chronic pain from trauma or neuropathy and has been shown to either stabilize or reduce opioid use in some patients with painful conditions. A more recently developed high-frequency SCS modality, 10 kHz SCS, has the advantage of being paresthesia-independent. It has been shown to be associated with significant reductions in opioid consumption after stimulation therapy was initiated, and many patients even taking high doses of opioids (> 90 mg morphine equivalent dose per day) were able to reduce their opioid intake to levels associated with less risk. The evidence shows that reduction of opioids as early in the treatment process as possible is desirable to reduce patient risk and improve pain relief from stimulation therapy.


Assuntos
Analgésicos Opioides , Dor Crônica , Idoso , Analgésicos Opioides/uso terapêutico , Dor Crônica/tratamento farmacológico , Dor Crônica/epidemiologia , Humanos , Medicare , Epidemia de Opioides , Melhoria de Qualidade , Medula Espinal , Estados Unidos/epidemiologia
9.
Curr Pain Headache Rep ; 24(6): 26, 2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-32335757

RESUMO

PURPOSE OF REVIEW: Low back and lower extremity pain have been treated since 1901 with local anesthetics alone and since 1952 in combination with steroids. Over the years, multiple randomized controlled trials, systematic reviews with or without meta-analysis have been reaching discordant conclusions regarding the effectiveness of sodium chloride solution, local anesthetics, and steroids in managing spinal pain. Further, related to lack of understanding, multiple reviewers have considered local anesthetics including lidocaine and bupivacaine as equivalent to placebo based on theory that steroid is the only drug effective in the epidural space. In this review, we assessed effectiveness of epidurally administered bupivacaine with or without steroids to rule out misconceptions of placebo and to show the comparative effectiveness of epidural bupivacaine alone compared to epidural bupivacaine with steroids. RECENT FINDINGS: Multiple systematic reviews performed in assessing the effectiveness of epidural injections have converted epidurally administered lidocaine and bupivacaine to placebo. This led to inappropriate conclusions of lack of effectiveness of epidural local anesthetics with or without steroids as showing equal effectiveness when analyzed with conventional dual-arm meta-analysis. Thus, true placebo control trials with injection of an inactive substance into unrelated structures have been almost non-existent. Epidurally administered bupivacaine alone or with steroids are effective in managing low back and lower extremity pain. The findings of this review provide appropriate information of epidurally administered bupivacaine as an active agent (not a placebo) with level 1 evidence and almost equally effective as bupivacaine with steroids with level II evidence.


Assuntos
Anestésicos Locais/administração & dosagem , Dor nas Costas/tratamento farmacológico , Bupivacaína/administração & dosagem , Dor Crônica/tratamento farmacológico , Esteroides/administração & dosagem , Dor nas Costas/diagnóstico , Dor Crônica/diagnóstico , Humanos , Injeções Epidurais , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos
10.
Curr Pain Headache Rep ; 24(6): 30, 2020 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-32468418

RESUMO

PURPOSE OF REVIEW: The growing prevalence of spinal pain in the USA continues to produce substantial economic impact and strain on health-related quality of life. Percutaneous adhesiolysis is utilized for recalcitrant, resistant conditions involving spinal pain when epidural injections have failed to provide adequate improvement, especially low back and lower extremity pain, specifically in post-lumbar surgery syndrome. Despite multiple publications and systematic reviews, the debate continues in reference to effectiveness, safety, appropriate utilization, and medical necessity of percutaneous adhesiolysis in chronic pain. This systematic review, therefore, was undertaken to evaluate and to update effectiveness of percutaneous adhesiolysis to treat chronic refractory low back and lower extremity pain, post-surgical patients of the lumbar spine. RECENT FINDINGS: From 2009 to 2016, there was a decline of 53.2% utilization of percutaneous adhesiolysis with an annual decline of 10.3% per 100,000 fee-for-service (FFS) Medicare population. Multiple insurers, including Medicare, with Medicare area contractors of Noridian and Palmetto have issued noncoverage policies for percutaneous adhesiolysis resulting in these steep declines and continued noncoverage by Medicare Advantage plans, Managed Care plans of Medicaid, and other insurers. Since 2005, 4 systematic reviews of percutaneous adhesiolysis were published with 3 of them showing proper methodology and appropriate results with effectiveness of adhesiolysis, whereas one poorly performed systematic review showed negative results. In addition, there were only 4 randomized controlled trials (RCTs) to be included in the previous systematic reviews of post-surgery syndrome, whereas now, the RCTs and other studies have increased. This systematic review shows level I or strong evidence for the effectiveness of percutaneous adhesiolysis in managing chronic low back and lower extremity pain related to post-lumbar surgery syndrome.


Assuntos
Dor Crônica/terapia , Dor Lombar/terapia , Extremidade Inferior , Manejo da Dor/métodos , Dor Pós-Operatória/terapia , Dor Crônica/diagnóstico , Humanos , Dor Lombar/diagnóstico , Extremidade Inferior/patologia , Vértebras Lombares , Estudos Observacionais como Assunto/métodos , Dor Pós-Operatória/diagnóstico , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Síndrome , Resultado do Tratamento
11.
Int J Mol Sci ; 21(17)2020 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-32842609

RESUMO

Tryptophan (TRP) is an essential, aromatic amino acid catabolized by indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) enzymes into kynurenine. The IDO enzyme is expressed in peripheral tissues and the central nervous system. Another enzyme of interest in the kynurenine signaling pathway is kynurenine 3-monooxygenase (KMO). The purpose of this review is to discuss the role of TRP and the kynurenine signaling pathway in different chronic pain patients. The IDO-1, IDO-2, and KMO enzymes and the kynurenine metabolite have been shown to be involved in the pathogenesis of neuropathic pain and other painful conditions (migraine, cluster headache, etc.) as well as depressive behavior. We highlighted the analgesic potential of novel agents targeting the enzymes of the kynurenine signaling pathway to explore their efficacy in both future basic science and transitional studies. Upcoming studies conducted on animal models will need to take into consideration the differences in TRP metabolism between human and non-human species. Since chronic painful conditions and depression have common pathophysiological patterns, and the kynurenine signaling pathway is involved in both of them, future clinical studies should aim to have outcomes targeting not only pain, but also functionality, mood changes, and quality of life.


Assuntos
Analgésicos/farmacologia , Dor Crônica/tratamento farmacológico , Dor Crônica/metabolismo , Cinurenina/metabolismo , Analgésicos/uso terapêutico , Animais , Depressão/metabolismo , Cefaleia/metabolismo , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Quinurenina 3-Mono-Oxigenase/metabolismo , Terapia de Alvo Molecular/métodos , Neuralgia/metabolismo , Especificidade da Espécie , Triptofano/metabolismo
12.
Curr Pain Headache Rep ; 23(5): 32, 2019 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-30888546

RESUMO

PURPOSE OF REVIEW: With an aging population and increased prevalence of the disease, we set out to evaluate the validity of current diagnostic criteria for neurogenic claudication as well as the efficacy of the treatment options for the main cause, lumbar spinal stenosis (LSS). RECENT FINDINGS: Epidural steroid injections (ESI) were most efficacious when the injectate is a steroid combined with lidocaine or lidocaine only. There are promising results regarding the efficacy of the minimally invasive lumbar decompression (MILD) procedure as well as interspinous process spacers (IPS) compared to surgical alternatives. Spinal cord stimulators are gaining ground as an effective alternative to surgery in patients with lumbar spinal stenosis that is not responsive to conservative measures or epidural injections. We found that there continues to be a lack of consensus on the diagnostic criteria, management, and treatment options for patients with LSS. The Delphi consensus is the most current recommendation to assist clinicians with making the diagnosis. Physical therapy, NSAIDs, gabapentin, and other conservative therapy measures are unproven in providing long-lasting relief. In patients with radicular symptoms, an ESI may be indicated when a combination of lidocaine with steroids is used or using lidocaine alone. In addition, there is not enough high-quality evidence to make a recommendation regarding the use of MILD versus interspinous spacers for neurogenic claudication. There remains a need for high-quality evidence regarding the efficacy of different conservative treatments, interventional procedures, and surgical outcomes in patients with neurogenic claudication in LSS.


Assuntos
Dor nas Costas/terapia , Manejo da Dor , Estenose Espinal/terapia , Descompressão Cirúrgica/métodos , Humanos , Vértebras Lombares/cirurgia , Manejo da Dor/métodos , Resultado do Tratamento
13.
Int J Mol Sci ; 20(22)2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31731606

RESUMO

Ovarian hormones play an important role in pain perception, and are responsible, at least in part, for the pain threshold differences between the sexes. Modulation of pain and its perception are mediated by neurochemical changes in several pathways, affecting both the central and peripheral nervous systems. One of the most studied neurotransmitters related to pain disorders is serotonin. Estrogen can modify serotonin synthesis and metabolism, promoting a general increase in its tonic effects. Studies evaluating the relationship between serotonin and disorders such as irritable bowel syndrome, fibromyalgia, migraine, and other types of headache suggest a clear impact of this neurotransmitter, thereby increasing the interest in serotonin as a possible future therapeutic target. This literature review describes the importance of substances such as serotonin and ovarian hormones in pain perception and illustrates the relationship between those two, and their direct influence on the presentation of the aforementioned pain-related conditions. Additionally, we review the pathways and receptors implicated in each disorder. Finally, the objective was to stimulate future pharmacological research to experimentally evaluate the potential of serotonin modulators and ovarian hormones as therapeutic agents to regulate pain in specific subpopulations.


Assuntos
Estrogênios/metabolismo , Dor/metabolismo , Serotonina/metabolismo , Animais , Fibromialgia/metabolismo , Humanos , Síndrome do Intestino Irritável/metabolismo , Transtornos de Enxaqueca/metabolismo
15.
J Therm Biol ; 74: 1-5, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29801613

RESUMO

Ketamine and magnesium as NMDA receptor antagonists interact synergistically to decrease body temperature in rats. The mechanism of the hypothermic effect of the ketamine-magnesium sulfate combination has not been studied until now. The aim of this study was to examine whether nitric oxide (NO) has a role in the hypothermic effect of ketamine (10 mg/kg) and the combination of ketamine (5 mg/kg) and magnesium sulfate (5 mg/kg). The body temperature was measured by insertion of a thermometer probe 5 cm into the colon of unrestrained male Wistar rats (200-250 g). N(ω)-nitro-L-arginine methyl ester (L-NAME 2.5 and 5 mg/kg) as non-selective inhibitor of nitric oxide synthase at a dose of 5 mg/kg antagonized the effect of the ketamine-magnesium sulfate combination at 60 min (p < 0.05) and 90 min (p < 0.01). Ketamine induced hypothermia was not affected by administrating of L-NAME (2.5 and 5 mg/kg). Inhibitor of inducible nitric oxide synthase N6-(1-Iminoethyl)-L-lysine hydrochloride (L-NIL 1.25 mg/kg and 2.5 mg/kg, sc) did not significantly change the hypothermic response evoked by the ketamine-magnesium sulfate combination. Inhibitor of neuronal nitric oxide synthase N-ω-Propyl-L-arginine hydrochloride (L-NPA) at a dose of 2 mg/kg antagonized the combination at 60 min when it achieved the maximum effect. The NO pathway is not involved in the hypothermic effect of ketamine. Production of NO through neuronal NO synthase, might play a role in the mechanism of the hypothermic effect of the ketamine-magnesium sulfate combination.


Assuntos
Hipotermia/induzido quimicamente , Ketamina/administração & dosagem , Sulfato de Magnésio/administração & dosagem , Óxido Nítrico Sintase Tipo I/antagonistas & inibidores , Animais , Temperatura Corporal/efeitos dos fármacos , Inibidores Enzimáticos/administração & dosagem , Masculino , NG-Nitroarginina Metil Éster/administração & dosagem , Ratos Wistar , Receptores de N-Metil-D-Aspartato/agonistas
16.
Int J Mol Sci ; 19(6)2018 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-29890676

RESUMO

It is estimated that the total annual financial cost for pain management in the U.S. exceeds 100 billion dollars. However, when indirect costs are included, such as functional disability and reduction in working hours, the cost can reach more than 300 billion dollars. In chronic pain patients, the role of pharmacogenetics is determined by genetic effects on various pain types, as well as the genetic effect on drug safety and efficacy. In this review article, we discuss genetic polymorphisms present in different types of chronic pain, such as fibromyalgia, low back pain, migraine, painful peripheral diabetic neuropathy and trigeminal neuralgia. Furthermore, we discuss the role of CYP450 enzymes involved in metabolism of drugs, which have been used for treatment of chronic pain (amitriptyline, duloxetine, opioids, etc.). We also discuss how pharmacogenetics can be applied towards improving drug efficacy, shortening the time required to achieve therapeutic outcomes, reducing risks of side effects, and reducing medical costs and reliance upon polypharmacy.


Assuntos
Dor Crônica/genética , Polimorfismo Genético , Analgésicos/uso terapêutico , Dor Crônica/tratamento farmacológico , Humanos , Manejo da Dor , Farmacogenética
18.
Anesth Analg ; 125(5): 1714-1732, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29049116

RESUMO

Opioids represent an efficacious therapeutic modality for some, but not all pain states. Singular reliance on opioid therapy for pain management has limitations, and abuse potential has deleterious consequences for patient and society. Our understanding of pain biology has yielded insights and opportunities for alternatives to conventional opioid agonists. The aim is to have efficacious therapies, with acceptable side effect profiles and minimal abuse potential, which is to say an absence of reinforcing activity in the absence of a pain state. The present work provides a nonexclusive overview of current drug targets and potential future directions of research and development. We discuss channel activators and blockers, including sodium channel blockers, potassium channel activators, and calcium channel blockers; glutamate receptor-targeted agents, including N-methyl-D-aspartate, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, and metabotropic receptors. Furthermore, we discuss therapeutics targeted at γ-aminobutyric acid, α2-adrenergic, and opioid receptors. We also considered antagonists of angiotensin 2 and Toll receptors and agonists/antagonists of adenosine, purine receptors, and cannabinoids. Novel targets considered are those focusing on lipid mediators and anti-inflammatory cytokines. Of interest is development of novel targeting strategies, which produce long-term alterations in pain signaling, including viral transfection and toxins. We consider issues in the development of druggable molecules, including preclinical screening. While there are examples of successful translation, mechanistically promising preclinical candidates may unexpectedly fail during clinical trials because the preclinical models may not recapitulate the particular human pain condition being addressed. Molecular target characterization can diminish the disconnect between preclinical and humans' targets, which should assist in developing nonaddictive analgesics.


Assuntos
Analgésicos não Narcóticos/uso terapêutico , Analgésicos Opioides/uso terapêutico , Descoberta de Drogas/métodos , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Dor/prevenção & controle , Pesquisa Translacional Biomédica/métodos , Analgésicos não Narcóticos/efeitos adversos , Analgésicos não Narcóticos/química , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/química , Animais , Composição de Medicamentos , Humanos , Terapia de Alvo Molecular , Transtornos Relacionados ao Uso de Opioides/diagnóstico , Transtornos Relacionados ao Uso de Opioides/etiologia , Dor/etiologia , Dor/fisiopatologia , Dor/psicologia , Percepção da Dor/efeitos dos fármacos , Limiar da Dor/efeitos dos fármacos , Fenótipo , Fatores de Risco , Transdução de Sinais/efeitos dos fármacos
19.
Curr Pain Headache Rep ; 21(2): 12, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28265859

RESUMO

PURPOSE OF REVIEW: Cancer pain is often incapacitating and discouraging to patients; is demoralizing to family members and care takers; and is taxing and difficult to subdue for the pain specialists. The consequences of implementing suboptimal treatment are far-reaching; therefore, effective treatment methods are in a great demand. The face of cancer pain management has changed in considerable ways, and interventional procedures have become an integral part of providing multimodal analgesia in cancer pain treatment. The goals of this review are to draw attention to the critical role that regional anesthetic nerve blocks and interventional pain management techniques play in treating malignancy-related pain and emphasize the benefits provided by the aforementioned treatment strategies. RECENT FINDINGS: A large proportion of cancer patients continues to struggle with an inadequately treated pain despite a strict adherence to the WHO analgesic step ladder. The previous pain treatment algorithm has been modified to include peripheral neural blockade, neuro-destructive techniques, neuromodulatory device use, and intrathecal drug delivery systems. The accumulated evidence highlights the opioid-sparing qualities and other benefits afforded by these modalities: decreasing medication-induced side effects, reducing economic burden of poor analgesia, and overall improvement in quality of life of the patients afflicted with a painful neoplastic disease. The rising prevalence of cancer-related pain syndromes is paralleled by an unmatched growth of innovative treatment strategies. Modified WHO analgesic ladder represents one of the greatest paradigm shifts within the domain of oncologic pain treatment. The cancer patient population requires a prompt and liberal, albeit judicious, delivery of unorthodox pain treatment options freed from the rigid bonds of conventional guidelines and standard practices.


Assuntos
Dor do Câncer/terapia , Manejo da Dor/métodos , Humanos
20.
Am J Ther ; 23(2): e489-97, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-24914505

RESUMO

According to the Food and Drug Administration (FDA) reports, approximately 8 in 10 prescriptions filled in the United States are for generic medications, with an expectation that this number will increase over the next few years. The impetus for this emphasis on generics is the cost disparity between them and brand-name products. The use of FDA-approved generic drugs saved 158 billion dollars in 2010 alone. In the current health care climate, there is continually increasing pressure for prescribers to write for generic alternative medications, occasionally at the expense of best clinical practices. This creates a conflict wherein both physicians and patients may find brand-name medications clinically superior but nevertheless choose generic ones. The issue of generic versus brand medications is a key component of the discussion of health payers, physicians and their patients. This review evaluates some of the important medications in the armamentarium of pain physicians that are frequently used in the management of chronic pain, and that are currently at the forefront of this issue, including Opana (oxymorphone; Endo Pharmaceuticals, Inc., Malvern, PA), Gralise (gabapentin; Depomed, Newark, CA), and Horizant (gabapentin enacarbil; XenoPort, Santa Clara, CA) that are each available in generic forms as well. We also discuss the use of Lyrica (pregabalin; Pfizer, New York, NY), which is currently unavailable as generic medication, and Cymbalta (duloxetine; Eli Lilly, Indianapolis, IN), which has been recently FDA approved to be available in a generic form. It is clear that the use of generic medications results in large financial savings for the cost of prescriptions on a national scale. However, cost-analysis is only part of the equation when treating chronic pain patients and undervalues the relationships of enhanced compliance due to single-daily dosing and stable and reliable pharmacokinetics associated with extended-duration preparations using either retentive technologies or delayed absorption strategies. Medications given to chronic pain patients should be individualized to best serve analgesic needs and assure patient safety primarily, based on high levels of scientific and economic evidence. Decisions regarding utilization should not be made based solely on limited or faulty assessments of cost-benefit analyses.


Assuntos
Dor Crônica/tratamento farmacológico , Medicamentos Genéricos/uso terapêutico , Aminas/uso terapêutico , Carbamatos/uso terapêutico , Ácidos Cicloexanocarboxílicos/uso terapêutico , Cloridrato de Duloxetina/uso terapêutico , Gabapentina , Humanos , Oximorfona/uso terapêutico , Pregabalina/uso terapêutico , Ácido gama-Aminobutírico/análogos & derivados , Ácido gama-Aminobutírico/uso terapêutico
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