Acute Pain Syndrome Research Articles

Rupture of the left rectus abdominis muscle due to COVID-19 related cough

Throughout the coronavirus disease 2019 pandemic, patients using oral anticoagulants for mechanical valve replacement and/or another clinical-pathological condition might have faced various clinical scenarios. Rectus sheath hematoma is one of the acute abdominal pain syndromes. This study presented a patient with developed anticoagulation-induced rectus sheath hematoma after mitral valve replacement.

Photobiomodulation of acute pain syndrome after septoplasty

The paper evaluates the effectiveness of the use of therapeutic laser exposure (photobiomodulation therapy – PBMT) to minimize acute pain in the early postoperative period in patients after septoplasty. The study included two groups of patients. Patients of the first group (31 patients) underwent septoplasty with standard management in the postoperative period. Patients of the second group (31 patients) also underwent septoplasty, and then added PBMT to the standard measures of the postoperative period at 3, 6 and 24 h after septoplasty (λ = 0.890 μm, P = 10 W, 2 min) and then intranasally 48 h after septoplasty (λ = 0.630 μm, P = 8 W, 2 min). In patients of both groups, heart rate variability and pain were assessed using a visual analog scale within 48 hours after septoplasty. In patients of the second group, after the use of PBMT, the indicators of heart rate variability had a significantly lower total power, compared with patients of the first group. So, after PBMT, the ultra-low-frequency component of the spectral analysis of heart rate variability in the first group was 18580 ± 2067 ms2, which is significantly higher than in the second group (8086 ± 3003 ms2) (p <0.001). The low-frequency component of heart rate variability was also significantly higher in the first group (1871 ± 405 ms2) compared to the second (1095 ± 190 ms2) (p <0.005), which indicates an increase in the tension of the sympathetic part of the autonomic nervous system in the group without the use of PBMT. In the first 3 hours after surgery, the severity of pain between the groups did not differ significantly (p = 0.07). In the period from 6 to 24 hours after surgery, patients who did not undergo PBMT experienced significantly higher pain than patients with PBMT (p <0.001). Thus, in our study, the group of patients with PBMT showed better results in pain and heart rate variability compared to the classical rehabilitation of patients after septoplasty.

Ramipril Alleviates Oxaliplatin-Induced Acute Pain Syndrome in Mice.

Oxaliplatin is a key drug for colorectal cancer that causes OXP-induced peripheral neuropathy, a dose-limiting effect characterized by cold and tactile hyperesthesia. The relationship between the sensory nervous system and modulation of the renin-angiotensin system has been described, focusing on pain and neurodegeneration in several animal models. We assessed the effect of the RAS modulator, ramipril, an angiotensin converting-enzyme inhibitor in a mouse model of OXP-induced acute pain syndrome. OXP was administered in Swiss mice at a cumulative dose of 15 mg/kg (3 x 5 mg/kg/3 days, i.p.). RAM was administered i.p. every day from 24 h before the first OXP injection until the end of the experiments. We evaluated OIAS development and treatment effects by sensorimotor tests, intraepidermal nerve fiber and dorsal root ganglia-neuron immunohistochemical analyses, and sciatic nerve ultrastructural analysis. OXP-treated mice showed tactile allodynia and cold hypersensitivity, without motor impairment and evidence of nerve degeneration. RAM prevented cold sensitivity and improved recovery of normal tactile sensitivity in OXP-treated mice. Our finding that RAM alleviates OXP-induced pain is a step towards evaluating its therapeutic potential in patients receiving OXP treatment.

P 53. Galvanic labyrinth polarization for holistic musculoskeletal therapy

Introduction. Acute and chronic pain syndromes of the spine are caused by multiple factors. Often pain syndromes are induced by imbalanced posture due to defective position in facette joints of the spine and by pathological stress of the autochthone and spinal muscles and tendons. From this a vicious circle follows. Due to high permanent pressure on one side and high permanent pull on the other, pain induced by inflammation and finally structural lesions of the bone develop. In this study the application of galvanic labyrinth polarization (Swing Symphonie) is used to interrupt the mentioned circuit of imbalance and pain. Material and Methods. Tests were performed on 14 subjects. All subjects were free of any cardiovascular, CNS, cochlear or vestibular disorder. Further, the integrity of the peripheral vestibular system was examined by head impulse testing (Halmagyi & Curthoys, 1988; Halmagyi et al., 1990) and additional one-sided galvanic labyrinth stimulation in combination with oculography, both of which confirmed the healthy vestibular status of the volunteers. In two pilot series Swing Symphonie was employed. In series 1 (n=10) the effect to stress relaxation and autonomic function were examined. Before and after stimulation a questionnaire had to be filled. Also, skin resistance, heart rate and respiratory frequency were measured. In series 2 (n=5x3) the effect to pain reduction was examined. Five subjects were investigated three times. Two subjects suffered from headache, three from spinal pain induced by degenerative disease. For series 2 the common diagnostic tests and scans were performed beforehand. No necessary therapy was missed. Swing Symphonie to the inner ear does not influence the labyrinth or cochlea as such, but rather the activity of the neurons in the vestibular nerve at the postsynaptic membrane (Goldberg et al., 1982, 1984; Smith &Goldberg, 1986; Schlosser, 1999). Sinusoidal stimulation was employed throughout the study. Electrodes were attached to the right and left mastoids and two additional electrodes were attached interscapular just medial to the superior angulus of the scapula A 2.0-Hz sinusoidal waveform was used to drive the current output of a custom-manufactured stimulator (Neurotronix, Berlin, Germany). In all cases, pendular perception was accompanied by ocular response (videooculography), demonstrating adequate vestibular stimulation. Results . In series 1, subjects reported to feel relaxed (8/10), comfortable (9/10) and calmed (6/10) after Swing Symphonie. Heart rate (9/10) and Skin resistance (8/10) decreased significantly. In series 2 after Swing Symphonie subjects reported a distinct reduction of pain symptoms (15/15). Discussion. In this pilot study Swing Symphonie induces relaxation and relieves pain syndromes. A pain inhibiting mechanism on the level of the posterior insula has to be discussed.

Risk factor analysis for taxane-associated acute pain syndrome under the dexamethasone prophylaxis.

Taxane-associated acute pain syndrome (T-APS) reportedly occurs in approximately 70% of patients undergoing therapy. We have previously reported that additional dexamethasone (DEX) administration attenuates T-APS. The aim of this study was to reveal risk factor(s) associated with the incidence of T-APS under prophylactic DEX administration. In total, 143 patients with breast cancer who received docetaxel (75mg/m2) or paclitaxel (175mg/m2)-containing treatment regimens were enrolled. DEX (4-8mg) was orally administered on days 2-4. Risk factors for the incidence of ≥ G2 and all-grade T-APS, as well as T-APS incidence between taxane-containing regimens in the first cycle, were retrospectively evaluated. Approximately 90% of the patients received taxanes for adjuvant or neoadjuvant chemotherapy. Overall, 55% of patients administered 4mg DEX, whereas 45% received 8mg DEX. Pegfilgrastim was administered in 27% of patients. Incidence of ≥ G2 and all-grade T-APS was 23.8%, and 69.2%, respectively. Univariate and multivariate analyses revealed that administration of pegfilgrastim is an independent risk factor for the incidence of ≥ G2 and all-grade T-APS; age younger than 55years is also a risk factor for all-grade T-APS. Moreover, the incidence of ≥ G2 and all-grade T-APS was 45.5% and 81.8% in a paclitaxel regimen, and 22.0% and 68.2% in docetaxel-including regimens, respectively, revealing increased tendency with paclitaxel administration, with no significant differences. Pegfilgrastim co-administration is an independent risk factor for ≥ G2 and all-grade T-APS, and age younger than 55years is a risk factor of all-grade T-APS under prophylactic DEX administration.

EVALUATION OF THE EFFECTIVENESS OF COMBINING ANALGESICS AND ANTISPASMODICS IN THE MANAGEMENT OF ABDOMINAL PAIN IN URGENT SURGERY

Acute abdominal pain, a set of symptoms developing in patients having pathology of the gastrointestinal tract, abdominal cavity and retroperitoneal space, is known as one of the leading causes for surgical hospitalization both in Ukraine and abroad. The aim of this study was to evaluate the effects of a combination drug "Neospastil", which belongs to the group of antispasmodics in combination with analgesics, on the severity of symptoms of abdominal spastic pain in order to improve the treatment of patients. This clinical study included 90 patients with a clinical picture of abdominal pain syndrome, who were hospitalized to the surgical departments. The patients were divided into 3 groups, 30 patients in each. We used various options for antispasmodic and analgesic therapy and compared their effectiveness in terms of the time of the onset of the analgesic effect, the time period of relieving abdominal spasm, and the duration of the periods between repeated spastic pain attacks. The results of our study demonstrated the use of the combined drug "Neospastil" in the management of acute abdominal pain syndrome even in the first day enabled to reduce the severity of the pain syndrome by 38% compared with the drotaverine therapy and by 19% compared with analogues of the combined drugs. The period of the occurrence of subsequent spastic pains was prolonged with the study drug by 2.2 ± 0.5 hours compared with drotaverine and by 1.1 ± 0.1 hours compared with spasmalgon. When using “Neospastil”, a decrease in the duration of an attack of abdominal spasm was noted by 29% compared with drotaverine and by 22% compared with spasmalgon. Summarizing the obtained data, we can recommend the use of “Neospastil” for the primary therapy of abdominal spastic pain in surgical patients that will lead to an improvement in the clinical treatment outcomes.

Анализ ассортимента наркотических лекарственных препаратов, применяемых для терапии болевого синдрома у онкологических больных в отделении паллиативной помощи

A study of the assortment of narcotic drugs for the relief of acute and chronic pain syndrome in cancer patients in the palliative care unit of the Oncological Center was carried out. It has been shown that practically all registered dosage forms of opioid analgesics are used

Malnutrition in hospitalized older patients. Clinical case

Malnutrition is a common geriatric syndrome, which often undiagnosed, leads to impaired physical and mental functioning and patient prognosis. Geriatric patients admitted to hospital with acute and subacute conditions and pain syndrome are in an especial risk zone. The article presents a clinical case of the development and correction of malnutrition in an 84-year-old patient with aseptic necrosis of the femoral head. Risk factors and existing approaches to the management of patients with malnutrition are discussed.

Efficacy of TENS in Cervical Pain Syndromes: An Umbrella Review of Systematic Reviews

Neck pain is defined as perceived pain, originating in an area bounded above by the nuchal line, below by an imaginary line passing through the spinous process of T1 and laterally by the sagittal plane tangent to the lateral edges of the neck. Our purpose is to investigate the effectiveness of transcutaneous electrical nerve stimulation (TENS) in patients suffering from both acute and chronic cervical pain syndromes. The literature research was conducted by consulting the following databases: PubMed, PEDro, Cochrane, and Google Scholar. To formulate the scientific question correctly, the PICO model was used. This umbrella review includes all systematic reviews with or without meta-analysis, in English, which analyze the use of TENS in subjects suffering from acute or chronic cervical pain. To evaluate the methodological quality of the studies, the AMSTAR model. A total of eleven systematic reviews with or without meta-analyses were included. The results of the study show how TENS seems to have an effect in reducing the intensity of acute and chronic cervical pain, especially in the short term. However, it was not possible to provide precise recommendations in this regard. Based on our result, it is desirable to carry out further studies that support the effectiveness of using TENS in patients suffering from acute and chronic neck pain.

Effectiveness of Dry Needling with Percutaneous Electrical Nerve Stimulation of High Frequency Versus Low Frequency in Patients with Myofascial Neck Pain

Percutaneous nerve electrical stimulation is a novel treatment modality for the management of acute and chronic myofascial pain syndrome. To compare the effectiveness of dry needling combined with percutaneous electrical nerve stimulation of low frequency versus high frequency, in patients with chronic myofascial neck pain. Randomized, single-blind trial. Laboratory in an academic institution. A total of 40 volunteer patients with chronic neck pain were randomly divided into 2 groups. All patients initially received deep dry needling in a myofascial trigger point of the upper trapezius. Then, one group received high frequency percutaneous electrical nerve stimulation while the other group received low frequency percutaneous electrical nerve stimulation. The primary outcomes were the visual analog scale and the pressure pain threshold, while Neck Disability Index and Kinesiophobia were secondary outcomes. We detected significant improvements in the visual analog scale score in both groups without differences between them. We did not observe significantly different statistics in either group during the evaluation of data on pressure pain threshold. Limitations of the study include (1) heterogeneity of the sample in relation to gender, with more women, (2) the small sample size (40 patients), (3) the absence of placebo group, and (4) the fact that the treatment is focused exclusively on the upper trapezium myofascial trigger point. . Low and high frequency percutaneous electrical nerve stimulation combined with deep dry needling showed similar effects, since no differences between groups were observed on any of the outcome measures. High and low frequency of percutaneous electrical nerve stimulation generates changes on pain intensity and disability, but not on pressure pain threshold or fear of movement.

New aspects of pain management in acute and chronic inflammatory syndromes

Effective pain control is one of the first and most important challenges in medical practice. Non-steroidal anti-inflammatory drugs (NSAIDs) are the cornerstone of treatment for acute and chronic inflammatory pain syndromes. Of particular interest is a group of patients with a low risk of cardiovascular development and a low to moderate risk of gastrointestinal complications, for whom any NSAID may be recommended. Their choice may depend on the duration and severity of the inflammatory process. The most high analgesic potential have non-selective inhibitors of cyclooxygenase – diclofenac and ketoprofen. Modern technologies give great opportunities for modifying the active substance of NSAIDs and improvement of the drug dosage form in order to hasten their effects and enhance analgesic and anti-inflammatory effect of drugs. In the new form of diclofenac (Dialrapid sachet), sodium salt was replaced by potassium salt, which provided a high rate of both absorption of the active substance and action, comparable to that with intramuscular administration of the drug. It also expanded the possibilities of its use for acute pain and relapses of pain relief in exacerbation of chronic inflammatory diseases. The inclusion of lysine salt significantly changed the pharmacodynamics of ketoprofen. Unlike conventional ketoprofen, its lysine salts (Artrozilen and OKИ) are fast-dissolving compounds with neutral pH that do not irritate the mucous membrane of the gastrointestinal tract, which makes them suitable for long-term treatment of chronic inflammatory pain syndromes.

Comprehensive Review of Topical Analgesics for Chronic Pain.

Topical analgesics are a non-opioid option for the treatment of chronic pain conditions including neuropathic pain, musculoskeletal pain, and osteoarthritis. There are many topical medications available; however their efficacy is variable. This article reviews the various topical analgesics, their mechanisms of action, and their efficacy. Studies have found topical NSAIDs are useful in treating acute musculoskeletal pain syndromes (strains and sprains) and show some efficacy in treating hand and knee osteoarthritis (Derry et al. Cochrane Database Syst Rev 5:CD008609, 2017). Topical capsaicin 8% has been shown to be efficacious in the treatment of postherpetic neuralgia, painful diabetic peripheral neuropathy, and HIV-neuropathy (Derry et al. Cochrane Database Syst Rev 1:CD007393, 2017). Topical lidocaine has been widely studied and found to reduce pain in patients with postherpetic neuralgia (Knezevic et al. Pain Manag 7:537-58, 2017). Although many other topical analgesics are available, there is limited data to support the efficacy of other agents. Topical analgesics are a relatively benign treatment for chronic pain conditions including neuropathic pain, musculoskeletal, and myofascial pain. There is evidence to support the use of topical NSAIDs, high concentration topical capsaicin, and topical lidocaine for various painful conditions.

Digital technology for estimation of course of diseases with acute pain syndrome on the example of ankylosing spondylitis

<h3>ЦЕЛЬ ИССЛЕДОВАНИЯ</h3> Разработка цифровых инструментов для оценки течения анкилозирующего спондилита. <h3>МАТЕРИАЛ И МЕТОДЫ</h3> Создание цифровых диагностических инструментов осуществлялось в среде Visual Studio 2019 с использованием платформ Net Framework (PC) и Xamarin (Android) на языке программирования C#. Данные по общей заболеваемости населения анкилозирующим спондилитом получены из открытых статистических сборников ФГБУ «ЦНИИОИЗ» Министерства здравоохранения Российской Федерации. <h3>РЕЗУЛЬТАТ</h3> В рамках инициативного проекта разработана компьютерная программа ASDiaTest, а также ее мобильный аналог ASDiaTestMobile. Коллективом авторов получены свидетельства о регистрации, выданные Федеральной службой по интеллектуальной собственности. Функциональные возможности данных программ удовлетворяют потребностям ревматологической службы в рамках профессиональной деятельности врачей соответствующей специальности, поскольку они обеспечивают информационную поддержку принятия решений в вопросах диагностики состояния пациентов с анкилозирующим спондилитом с помощью оценочных индексов. <h3>ЗАКЛЮЧЕНИЕ</h3> Благодаря концепции, согласно которой уровень боли является субъективным отражением активности заболевания, оценка состояния больных с анкилозирующим спондилитом может производиться на доврачебном этапе медицинского обследования. Предполагается, что внедрение цифровых технологий для автоматического расчета оценочных индексов позволит снизить нагрузку на врача, что будет способствовать повышению качества диагностических мероприятий и эффективности работы ревматологической службы.

Clinical experience with the use of a fixed combination of diclofenac and orphenadrine in the treatment of acute pain syndrome

Nonsteroidal anti-inflammatory drugs (NSAIDs) and muscle relaxants (MR) are successfully used to relieve pain, both in monotherapy and in combinations. The use of fixed drug combinations not only greatly facilitates daily clinical practice and increases patient adherence, but due to the potentiation of pharmacological effects, it allows to achieve better treatment results. This paper presents 3 clinical cases of successful inpatient use of a fixed combination of diclofenac 75 mg and orphenadrine 30 mg in the form of an infusion solution (NEODOLPASSE) for relief of acute back musculoskeletal pain syndrome.

Fixed combination of orphenadrine and diclofenac in the treatment of acute spondylogenic pain syndromes

<h3>ЦЕЛЬ ИССЛЕДОВАНИЯ</h3> Сравнение обезболивающей эффективности и безопасности фиксированной комбинации диклофенака и орфенадрина с обезболивающей эффективностью и безопасностью декскетопрофена и толперизона у пациентов с острой неспецифической болью в шее, пояснице и у пациентов с шейной и поясничной радикалгией. <h3>МАТЕРИАЛ И МЕТОДЫ</h3> В исследование включены 36 пациентов в возрасте 30—60 лет с острой неспецифической болью в шее, пояснице, с шейной и поясничной радикалгией. Пациенты были рандомизированы в две группы. В 1-й группе неодолпассе (диклофенака 75 мг и орфенадрина 30 мг) вводился внутривенно ежедневно в течение 2 сут. С целью оптимизации лечения были выделены две подгруппы с однократным и двукратным введением неодолпассе в сутки. Во 2-й группе (сравнения) 21 пациенту проводилось внутримышечное введение декскетопрофена (50 мг дважды в сутки) и толперизона (100 мг ежедневно) в течение 3 сут. <h3>РЕЗУЛЬТАТЫ</h3> По визуально-аналоговой шкале (ВАШ) начальный уровень выраженности болевого синдрома был сопоставим в группах. Более выраженный анальгетический эффект отмечался после второго дня лечения у пациентов, которым осуществлялось введение неодолпассе. Получены данные о более выраженном анальгетическом эффекте при двукратном введении неодолпассе по сравнению с однократным введением в сутки. При ведении неодолпассе не было отмечено местных побочных явлений. Диспепсические расстройства (изжога, снижение аппетита) были выявлены у двух пациентов (5,5%). В одном случае отмечено появление головокружения и тремора после второй инъекции. После проведения внутривенной инфузии наиболее часто пациенты отмечали сонливость — в 4 (11,1%) случаях. При мониторировании артериального давления отмечалось незначительное повышение систолического давления непосредственно после проведения инфузии. Динамики диастолического давления не отмечалось, и оно оставалось стабильным в течение проводимого курса терапии. <h3>ЗАКЛЮЧЕНИЕ</h3> Использование фиксированной комбинации орфенадрина и диклофенака является высокоэффективным и безопасным методом лечения острых спондилогенных болевых синдромов. Применение препарата за счет воздействия на разные патогенетические механизмы сопровождается быстрым обезболивающим действием, что позволяет существенно уменьшить потребление анальгетических препаратов.

The Levels of Insulin-Like Growth Factor in Patients with Myofascial Pain Syndrome and in Healthy Controls.

Insulin-like growth factor-1 (IGF-1) plays an important role in muscle maintenance and repair. The role of IGF-2 in the muscle is less clear. To compare the levels of IGF-1 and IGF-2 in participants with acute myofascial pain syndrome (MPS) versus healthy controls and to determine whether age, gender, body mass index (BMI), region of pain, and pain intensity are associated with IGF levels. A case-control study design included a total of 74 participants. Hospital emergency department. Participants presenting with acute MPS (n = 43) and non-MPS controls (n = 31). Serum IGF-1 and IGF-2 (pg/mL) were measured in participants with MPS within 24 hours of symptom onset, and in non-MPS controls. Group and gender differences in serum IGF-1 and IGF-2 were assessed, with group and gender as factors, while controlling for age and BMI. The mean IGF-1 levels were not significantly different between MPS and controls (88 554.1, confidence interval [CI], 79 724.4-97 383.7 vs. 97 911.2, CI, 85 322.8-110 493.6). Significant differences were also not observed in IGF-1 levels between men and women with MPS nor between men and women in the control group. Mean levels of IGF-2 were significantly lower in patients with MPS than in controls (226 608.9, CI, 180 057.3-273 160.5 versus 460 343.9, CI, 387 809.4-532 878.2, P< .001). There were no significant gender differences in the levels of IGF-2 in patients with MPS. Mean IGF-2 levels (pg/mL) of men and women with MPS were lower (253 343.0, CI, 179 891.0-326 795.0, and 204 524.2, CI, 141 176.4-267 872.0, respectively) than those of healthy men and women (428 177.2, CI, 368 345.7-488 008.6, and 511 274.4, 355 178.6-687 370.1, respectively). Lower BMI and younger age were associated with higher levels of IGF-2. Pain intensity was associated with IGF-2 but not with IGF-1, whereas region of pain was not associated with either IGF-1 or IGF-2 levels. IGF-2 levels were lower in patients with acute MPS versus healthy controls with no gender differences, and IGF-1 levels were not different among the groups. Future studies should investigate the role of IGF-2 in muscle maintenance and repair in MPS.

Fascial Plane Blocks: More Questions Than Answers?

Fascial Plane Blocks: More Questions Than Answers?

Treatment of acute dysmenorrhoea and pelvic pain syndrome of uterine origin with myometrial botulinum toxin injections under hysteroscopy: A pilot study

BackgroundAcute dysmenorrhoea in women which has been shown to be anatomically negative for endometriosis is a very common condition. It is frequently associated with Chronic Pelvic Pain (CPP) from uterine origin, including painful uterine contractions and deep dyspareunia. We call this association Painful Uterine Syndrome (PUS). Search strategyIn these women in failure of the usual treatments, we proposed a new treatment, with Uterine Toxin Botulinic injections (BTX) under hysteroscopy, as a compassionate option, among women in severe pain and therapeutic failure.Indeed, increased uterine contractility has been confirmed using cine magnetic resonance imaging in patients with acute dysmenorrhea and PUS.These findings, associated with the hypothesis of a possible uterine sensitization on the same model as irritable bowel syndrome (IBS) or painful bladder syndrome (PBS), led to the application of botulinum toxin (BTX) injections under hysteroscopy of the uterine myometrium in this indication. Material and methodsIn 2018, we conducted an open-label non comparative study, on 30 patients, with severe dysmenorrhea and PUS in therapeutic failure situation.All women had failure of usual treatments, with painkillers, anti-inflammatory drugs, contraceptive pill, menstrual suppressant therapy and a negative MRI and laparoscopy.The BTX units (200 IU of Incobotulinum-toxin A) were evenly distributed in the anterior and posterior myometrial wall under hysteroscopic control.Patients were reviewed between 8 and 12 weeks after BTX injections and then, at 6 months. Main resultsMedian VAS scores were significantly improved at 8–12 weeks follow up for dysmenorrhoea, deep dyspareunia, and pelvic pain outside of menstruation. Quality of life scores all improved dramatically. No major side effect has been reported in this pilot study.At 6 months, 12 patients (40 %), were given new injections for pain reccurence. But 14 patients (47 %), were still improved and did not require repeat injection at that time.4 patients, were improvement was not significant, did not ask for repat BTX injections. These patients were all positive for Pelvic Sensitization criteria. ConclusionsUterine BTX injection could be a very interesting therapeutic option in women with acute dysmenorrheoa and PUS in therapeutic failure. Only long-term randomised studies will be able to confirm that BTX injections are useful as a treatment for this condition. The randomised long-term study, Uteroxine, will shortly release its results.

Lysophospholipids Contribute to Oxaliplatin-Induced Acute Peripheral Pain.

Oxaliplatin, a platinum-based chemotherapeutic drug, which is used as first-line treatment for some types of colorectal carcinoma, causes peripheral neuropathic pain in patients. In addition, an acute peripheral pain syndrome develop in almost 90% of patients immediately after oxaliplatin treatment, which is poorly understood mechanistically but correlates with incidence and severity of the later-occurring neuropathy. Here we investigated the effects of acute oxaliplatin treatment in a murine model, showing that male and female mice develop mechanical hypersensitivity 24 h after oxaliplatin treatment. Interestingly, we found that the levels of several lipids were significantly altered in nervous tissue during oxaliplatin-induced acute pain. Specifically, the linoleic acid metabolite 9,10-EpOME (epoxide of linoleic acid) as well as the lysophospholipids lysophosphatidylcholine (LPC) 18:1 and LPC 16:0 were significantly increased 24 h after oxaliplatin treatment in sciatic nerve, DRGs, or spinal cord tissue as revealed by untargeted and targeted lipidomics. In contrast, inflammatory markers including cytokines and chemokines, ROS markers, and growth factors are unchanged in the respective nervous system tissues. Importantly, LPC 18:1 and LPC 16:0 can induce Ca2+ transients in primary sensory neurons, and we identify LPC 18:1 as a previously unknown endogenous activator of the ligand-gated calcium channels transient receptor potential V1 and M8 (transient receptor potential vanilloid 1 and transient receptor potential melastatin 8) in primary sensory neurons using both pharmacological inhibition and genetic knockout. Additionally, a peripheral LPC 18:1 injection was sufficient to induce mechanical hypersensitivity in naive mice. Hence, targeting signaling lipid pathways may ameliorate oxaliplatin-induced acute peripheral pain and the subsequent long-lasting neuropathy.SIGNIFICANCE STATEMENT The first-line cytostatic drug oxaliplatin can cause acute peripheral pain and chronic neuropathic pain. The former is causally connected with the chronic neuropathic pain, but its mechanisms are poorly understood. Here, we performed a broad unbiased analysis of cytokines, chemokines, growth factors, and ∼200 lipids in nervous system tissues 24 h after oxaliplatin treatment, which revealed a crucial role of lysophospholipids lysophosphatidylcholine (LPC) 18:1, LPC 16:0, and 9,10-EpOME in oxaliplatin-induced acute pain. We demonstrate for the first time that LPC 18:1 contributes to the activation of the ion channels transient receptor potential vanilloid 1 and transient receptor potential melastatin 8 in sensory neurons and causes mechanical hypersensitivity after peripheral injection in vivo These findings suggest that the LPC-mediated lipid signaling is involved in oxaliplatin-induced acute peripheral pain.

Selective activation of metabotropic glutamate receptor 7 blocks paclitaxel-induced acute neuropathic pain and suppresses spinal glial reactivity in rats.

Paclitaxel-induced acute pain syndrome (P-APS), characterized by deep muscle aches and arthralgia, occurs in more than 70% of patients who receive paclitaxel. P-APS can be debilitating for patients and lead to reductions and discontinuation of potentially curable therapy. Despite being relatively common in clinical practice, no clear treatment exists for P-APS and the underlying mechanisms remain poorly defined. Regulation of glutamatergic transmission by metabotropic glutamate receptors (mGluRs) has received growing attention with respect to its role in neuropathic pain. To our knowledge, no study has been conducted on alterations and functions of group III mGluR7 signaling in P-APS. In the present study, we determined whether a single administration of paclitaxel induces glutamatergic alterations and whether mGluR7 activation blocks paclitaxel-induced neuropathic pain by suppressing glial reactivity in the spinal cord. A single paclitaxel injection dose-dependently induced acute mechanical and thermal hypersensitivity, and was associated with increased glutamate level accompanied by reduction in mGluR7 expression in the spinal cord. Selective activation of mGluR7 by its positive allosteric modulator, AMN082, blocked the development of paclitaxel-induced acute mechanical and thermal hypersensitivity, without affecting the normal pain behavior of control rats. Moreover, activation of mGluR7 by AMN082 inhibited glial reactivity and decreased pro-inflammatory cytokine release during P-APS. Abortion of spinal glial reaction to paclitaxel alleviated paclitaxel-induced acute mechanical and thermal hypersensitivity. There results support the hypothesis that spinal mGluR7 signaling plays an important role in P-APS; Selective activation of mGluR7 by its positive allosteric modulator, AMN082, blocks P-APS in part by reducing spinal glial reactivity and neuroinflammatory process.