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Pain in irritable bowel syndrome: Does anything really help?
BouSaba, J, Sannaa, W, Camilleri, M
Neurogastroenterology and motility. 2022;(1):e14305
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Abstract
Pain relief remains a significant challenge in the management of irritable bowel syndrome (IBS): "Does anything really help relieve the pain in patients with IBS?". Interventions aimed at pain relief in patients with IBS include diet, probiotics or antibiotics, antidepressants, antispasmodics, and drugs targeting specific gastrointestinal receptors such as opioid or histamine receptors. In the systematic review and meta-analysis published in this journal, Lambarth et al. examined the literature on the role of oral and parenteral anti-neuropathic agents in the management of pain in patients with IBS. This review article appraises their assessment of the efficacy of the anti-neuropathic agents amitriptyline, pregabalin, gabapentin, and duloxetine in the relief of abdominal pain or discomfort, and impact on overall IBS severity and quality of life. This commentary provides an update of current evidence on the efficacy of the dietary and pharmacological treatments that are available or in development, as well psychological and cognitive behavioral therapy for pain in IBS. Advances in recent years augur well for efficacious treatments that may expand the therapeutic arsenal for pain in IBS.
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Pattern of treatment of behavioural and psychological symptoms of dementia and pain: evidence on pharmacoutilization from a large real-world sample and from a centre for cognitive disturbances and dementia.
Scuteri, D, Vulnera, M, Piro, B, Bossio, RB, Morrone, LA, Sandrini, G, Tamburin, S, Tonin, P, Bagetta, G, Corasaniti, MT
European journal of clinical pharmacology. 2021;(2):241-249
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PURPOSE Data concerning the number of diagnoses and of the drugs prescribed to patients affected by dementia are still scarce. Here we test whether or not (1) prescription of symptomatic drugs against Alzheimer's disease (AD) may approximate the number of patients affected by dementia in Italy and (2) adherence to this treatment affects the pattern of prescription of drugs (i.e. antipsychotics and antidepressants) for behavioural and psychological symptoms of dementia (BPSD) and the previously reported limited prescription of analgesics. METHODS This retrospective observational study concerns 84,235 subjects older than 60 years and registered in the provincial prescription database of the health district of Cosenza accounting for a population of 298,000 inhabitants. The prescribing pattern of antipsychotics, antidepressants, and analgesics has been investigated in patients receiving concurrent prescriptions of acetylcholinesterase inhibitors (AChEI) and/or memantine. Data from a single centre for cognitive disturbances and dementia (CDCD) in the same health district were used to explore at which stage dementia was diagnosed. The study was approved by Calabria Region Ethical Committee no. 31/2017 and registered on October 31, 2017. RESULTS The data show that 859 patients are treated with AChEI and/or memantine; 420 patients (48.89%) receive at least 80% of the recommended medications. CDCD data indicate a delay in dementia diagnosis, which often was made when the patients were moderately to severely demented (Mini Mental State Examination, MMSE ≤ 20). Adherence did not influence prescription of most of the drugs explored, but use of non-steroidal anti-inflammatory drugs was higher in non-adherent patients. Antipsychotics and antidepressants are frequently used (20.61-20.71% and 42.37-51.43%, respectively), and this, at least in part, might stem from the observed under-treatment of chronic pain (opioids are prescribed in the 4.76% and 12.46% of adherent and non-adherent patients and gabapentin and pregabalin are used in the 4.29% and 4.07% of adherent and non-adherent patients respectively), resulting in more frequent BPSD. 16.43% of patients receive antipsychotics for longer than 6-12 weeks. CONCLUSION This 2-year period study, including a wide cohort of community demented patients, shows that dementia is diagnosed late and that prevalence of BPSD prescriptions is high and not impacted by adherence to anti-dementia drugs. The rate of prescription of potentially harmful antipsychotics and antidepressants appears to be high though whether the concomitantly observed limited prescription of analgesics might be a contributing factor needs to be further investigated. Our data support the development of strategies to improve the management of BPSD.
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Traditional Aspects of Sciatic Pain Management and Allied Therapies from Persian Medical Reports.
Ansari, R, Dadbakhsh, A, Hasani, F, Hosseinzadeh, F, Abolhassanzadeh, Z, Zarshenas, MM
Current drug discovery technologies. 2021;(2):194-206
Abstract
Sciatica is a common back pain caused by irritation of the sciatic nerve. Current pharmacologic therapies have proven inadequate for many patients with sciatic pain. On the other hand, there is a globally increasing demand for the use and administration of natural medicaments for this disorder. Traditional Persian Medicine (TPM) is a school of medicine and a medicinal plant-based resource for clinical studies put forward by Persian scholars. The aim of the present study is to gather and study the effectiveness of all medicinal plants from five main Persian pharmacopeias. Furthermore, different databases such as PubMed and Scopus have been checked to derive relevant activities for these plants. In all, 99 medicinal plants related to 42 families have been authenticated. Asteraceae and Apiaceae were the most frequent families and roots and seeds were the most reported botanical parts. The employed routes of administration were oral (54%), topical (33%) and rectal (13%). Anti-inflammatory, analgesic activity and antinociceptive properties of medicines are known as some main mechanisms to manage sciatic pain. These functions are possessed by 30%, 15%, and 15% of the studied plants, respectively. Medicaments that can be introduced as lead agents for further investigation are Zingiber officinale Roscoe, Olea europaea L., Strychnos nux-vomica L and Artemisia vulgaris L which showed all of these properties in previous studies. Hence, conducting adducible clinical trials using these lead agents may lead to novel drugs with lesser undesirable and much more therapeutic effects on controlling sciatic pain.
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Medical treatment of SUNCT and SUNA: a prospective open-label study including single-arm meta-analysis.
Lambru, G, Stubberud, A, Rantell, K, Lagrata, S, Tronvik, E, Matharu, MS
Journal of neurology, neurosurgery, and psychiatry. 2021;(3):233-241
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INTRODUCTION The management of short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA) remains challenging in view of the paucity of data and evidence-based treatment recommendations are missing. METHODS In this single-centre, non-randomised, prospective open-label study, we evaluated and compared the efficacy of oral and parenteral treatments for SUNCT and SUNA in a real-world setting. Additionally, single-arm meta-analyses of the available reports of SUNCT and SUNA treatments were conducted. RESULTS The study cohort comprised 161 patients. Most patients responded to lamotrigine (56%), followed by oxcarbazepine (46%), duloxetine (30%), carbamazepine (26%), topiramate (25%), pregabalin and gabapentin (10%). Mexiletine and lacosamide were effective in a meaningful proportion of patients but poorly tolerated. Intravenous lidocaine given for 7-10 days led to improvement in 90% of patients, whereas only 27% of patients responded to a greater occipital nerve block. No statistically significant differences in responders were observed between SUNCT and SUNA. In the meta-analysis of the pooled data, topiramate was found to be significantly more effective in SUNCT than SUNA patients. However, a higher proportion of SUNA than SUNCT was considered refractory to medications at the time of the topiramate trial, possibly explaining this isolated difference. CONCLUSIONS We propose a treatment algorithm for SUNCT and SUNA for clinical practice. The response to sodium channel blockers indicates a therapeutic overlap with trigeminal neuralgia, suggesting that sodium channels dysfunction may be a key pathophysiological hallmark in these disorders. Furthermore, the therapeutic similarities between SUNCT and SUNA further support the hypothesis that these conditions are variants of the same disorder.
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A triple-blind randomized clinical trial of different associations between dexamethasone and non-steroids anti-inflammatories for preemptive action in third molar extractions.
Momesso, GAC, Grossi-Oliveira, GA, Silva, WPP, Akira, R, Chiba, F, Polo, TOB, de Lima Neto, TJ, Rios, BR, Bassi, APF, Sumida, DH, et al
Scientific reports. 2021;(1):24445
Abstract
The aim of this study is to evaluate the preemptive analgesic effects of dexamethasone (DEX) alone or combined with non-steroidal anti-inflammatory drugs (NSAIDs) in third molar surgeries. The subjects were divided into five groups (n = 20 teeth/group); subjects received only 8 mg of dexamethasone 1 h before the surgical procedure (DEX group), or in combination with etodolac (DEX + ETO), ketorolac (DEX + KET), ibuprofen (DEX + IBU), loxoprofen (DEX + LOX). Paracetamol 750 mg was provided as the number of rescue analgesics (NRA). Salivary PGE2 expression was measured preoperatively and at 48 h. Edema and Maximum mouth opening (MMO) were measured postoperatively at 48 h and 7 days. A visual analog scale (VAS) was performed postoperatively at 6, 12, 24, 48, 72 h, and 7 days. Salivary expression of PGE2 showed a decrease only for the DEX group. Edema and MMO and NRA consumption showed no significant differences among the groups (P > 0.05). The VAS showed a significantly lower pain perception at 6 h after the surgery for the DEX + ETO and DEX + KET groups (P < 0.05). The combination of DEX and NSAIDS should be considered for preemptive acute postsurgical pain management in third molar surgery. In some drug associations such as dexamethasone 8 mg + NSAIDS (ETO and KET) in the pre-operative time, only a few rescue analgesics are necessary.
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Mechanisms, Characteristics, and Treatment of Neuropathic Pain and Peripheral Neuropathy Associated with Dinutuximab in Neuroblastoma Patients.
Mastrangelo, S, Rivetti, S, Triarico, S, Romano, A, Attinà, G, Maurizi, P, Ruggiero, A
International journal of molecular sciences. 2021;(23)
Abstract
Prognosis of metastatic neuroblastoma is very poor. Its treatment includes induction chemotherapy, surgery, high-dose chemotherapy, radiotherapy, and maintenance with retinoic acid, associated with the anti-GD2 monoclonal antibody (ch14.18) dinutuximab. Immunotherapy determined a significant improvement in survival rate and is also utilized in relapsed and resistant neuroblastoma patients. Five courses of dinutuximab 100 mg/m2 are usually administered as a 10-day continuous infusion or over 5 consecutive days every 5 weeks. Dinutuximab targets the disialoganglioside GD2, which is highly expressed on neuroblastoma cells and minimally present on the surface of normal human neurons, peripheral pain fibers, and skin melanocytes. Anti GD2 antibodies bind to surface GD2 and determine the lysis of neuroblastoma cells induced by immune response via the antibody-dependent cellular cytotoxicity and the complement-dependent cytotoxicity. Dinutuximab has significant side effects, including neuropathic pain, peripheral neuropathy, hypersensitivity reactions, capillary leak syndrome, photophobia, and hypotension. The most important side effect is neuropathic pain, which is triggered by the same antibody-antigen immune response, but generates ectopic activity in axons, which results in hyperalgesia and spontaneous pain. Pain can be severe especially in the first courses of dinutuximab infusion, and requires the administration of gabapentin and continuous morphine infusion. This paper will focus on the incidence, mechanisms, characteristics, and treatment of neuropathic pain and peripheral neuropathy due to dinutuximab administration in neuroblastoma patients.
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A randomized comparative study of methylcobalamin, methylcobalamin plus pregabalin and methylcobalamin plus duloxetine in patients of painful diabetic neuropathy.
Sharma, C, Kaur, I, Singh, H, Grover, IS, Singh, J
Indian journal of pharmacology. 2021;(5):358-363
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CONTEXT Diabetic neuropathy affects 10.5%-32.2% of diabetic population posing clinical burden onto society. AIMS We aimed to study the efficacy, safety, and tolerability of methylcobalamin, methylcobalamin plus pregabalin, and methylcobalamin plus duloxetine in patients of painful diabetic neuropathy. SETTINGS AND DESIGN It is a prospective, randomized, open-label, interventional, and parallel-group study done in patients of painful diabetic neuropathy. MATERIALS AND METHODS A total of 100 patients were recruited and randomized to three study groups A, B, and C on methylcobalamin, methylcobalamin and pregabalin, and methylcobalamin and duloxetine, respectively. Patients were assessed at day 0 and 4, 8, and 12 weeks. The tuning fork test, monofilament test, Thermal Sensitivity testing, and Visual Analog Scale (VAS) were used to analyze vibration, pressure, thermal sensitivity, and pain. STATISTICAL ANALYSIS USED The results are expressed as mean ± standard deviation. Appropriate statistical methods were used to calculate P value (<0.05 - significant). RESULTS The increase in number of patients with vibration perception is 11.6%, 37.9%, and 41.4%; pressure sensation is 7.6%, 37.9%, and 37.9%; and thermal sensitivity is 15.4%, 31.1%, and 37.9% in Groups A, B, and C, respectively. The decrease in VAS scores is 0.58 ± 0.14, 3.82 ± 0.05, and 4.17 ± 0.48 in Groups A, B, and C correspondingly. The adverse effects reported in Groups A, B, and C are 0%, 6.9%, and 10.3%, respectively. CONCLUSIONS Group C is more efficacious when compared to Groups A and B while Group B is safer.
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Pharmacological Insights into Halophyte Bioactive Extract Action on Anti-Inflammatory, Pain Relief and Antibiotics-Type Mechanisms.
Giordano, R, Saii, Z, Fredsgaard, M, Hulkko, LSS, Poulsen, TBG, Thomsen, ME, Henneberg, N, Zucolotto, SM, Arendt-Nielsen, L, Papenbrock, J, et al
Molecules (Basel, Switzerland). 2021;(11)
Abstract
The pharmacological activities in bioactive plant extracts play an increasing role in sustainable resources for valorization and biomedical applications. Bioactive phytochemicals, including natural compounds, secondary metabolites and their derivatives, have attracted significant attention for use in both medicinal products and cosmetic products. Our review highlights the pharmacological mode-of-action and current biomedical applications of key bioactive compounds applied as anti-inflammatory, bactericidal with antibiotics effects, and pain relief purposes in controlled clinical studies or preclinical studies. In this systematic review, the availability of bioactive compounds from several salt-tolerant plant species, mainly focusing on the three promising species Aster tripolium, Crithmum maritimum and Salicornia europaea, are summarized and discussed. All three of them have been widely used in natural folk medicines and are now in the focus for future nutraceutical and pharmacological applications.
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Ginger for Migraine.
Andrade, C
The Journal of clinical psychiatry. 2021;(6)
Abstract
Many preclinical and clinical studies have examined the potential benefits of ginger extracts for a range of medical disorders. Ginger has been found to reduce both pain and nausea and has therefore also been studied in the context of migraine headache. One randomized controlled trial (RCT) found that ginger was no better than placebo for the prevention of migraine episodes. One meta-analysis (pooled N = 227) found that, relative to placebo, ginger was associated with a higher proportion of patients who were pain free 2 hours after treatment (risk ratio [RR], 1.79; 95% confidence interval [CI], 1.04-3.09; 2 RCTs). In this meta-analysis, relative to placebo, ginger reduced the risk of migraine-related nausea and vomiting (RR, 0.48; 95% CI, 0.30-0.77; 3 RCTs) and was not associated with an increased risk of adverse events (RR, 0.80; 95% CI, 0.46-1.41; 3 RCTs). No other RCT data are available. Such an evidence base is clearly too small for formal recommendations to be possible. It is suggested that raw ginger or proprietary ginger extracts may be useful as a home remedy for patients who experience an episode of migraine and who, for whatever reason, cannot take established first-line treatments for acute migraine. How ginger thus used compares with established treatments for migraine is presently unknown. Finally, it must be remembered that the chemical constituents of ginger will vary across source and extract; so, when an extract of ginger is studied, the findings of the study can be generalized only to that extract and, possibly, to other extracts with a similar composition.
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Lack of Detection of the Analgesic Properties of PF-05089771, a Selective Nav 1.7 Inhibitor, Using a Battery of Pain Models in Healthy Subjects.
Siebenga, P, van Amerongen, G, Hay, JL, McDonnell, A, Gorman, D, Butt, R, Groeneveld, GJ
Clinical and translational science. 2020;(2):318-324
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Sodium channel blockers are used for the treatment of pain, but this is limited by the lack of selectivity for different sodium channel subtypes, which can result in central nervous system and cardiovascular side effects. As such, there is special interest in the Nav 1.7 subtype, which is expressed predominantly in nociceptive and sympathetic neurons. The aim was to demonstrate analgesic properties of a potent selective Nav 1.7 sodium channel blocker, PF-05089771, alone and concomitantly with pregabalin in healthy subjects using a battery of human evoked pain models. This was a double-blind, double-dummy, randomized, placebo-controlled, five-period cross-over study with PF-05089771 alone and PF-05089771 concomitantly with pregabalin as treatment arms with pregabalin, ibuprofen, and placebo as control arms (NCT02349607). A battery of human evoked pain models was used to investigate analgesic properties of PF-05089771. Twenty-five subjects were enrolled in the study of which 23 subjects completed all five periods. PF-05089771 alone did not differ from placebo on the primary pain end points. The same holds when comparing PF-05089771 concomitantly with pregabalin and pregabalin alone. Pregabalin showed significant effects relative to placebo on thermal pain on the normal skin and UVB skin (least squares means with 90% confidence interval: 0.63 (0.32-0.93) and 0.53 (0.11-0.96)), pressure stimulation (1.10 (1.04-1.18)), and cold pressor (1.22 (1.14-1.32)). Ibuprofen demonstrated significant effects on thermal pain UVB skin (1.26 (0.82-1.70)) and pressure stimulation assessment (1.08 (1.01-1.15)), consistent with historical results. This study did not demonstrate analgesic properties of PF-05089771 alone or concomitantly with pregabalin in a battery of pain models.