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Current understanding of the mixed pain concept: a brief narrative review.
Freynhagen, R, Parada, HA, Calderon-Ospina, CA, Chen, J, Rakhmawati Emril, D, Fernández-Villacorta, FJ, Franco, H, Ho, KY, Lara-Solares, A, Li, CC, et al
Current medical research and opinion. 2019;(6):1011-1018
Abstract
Despite having been referenced in the literature for over a decade, the term "mixed pain" has never been formally defined. The strict binary classification of pain as being either purely neuropathic or nociceptive once left a good proportion of patients unclassified; even the recent adoption of "nociplastic pain" in the IASP Terminology leaves out patients who present clinically with a substantial overlap of nociceptive and neuropathic symptoms. For these patients, the term "mixed pain" is increasingly recognized and accepted by clinicians. Thus, an independent group of international multidisciplinary clinicians convened a series of informal discussions to consolidate knowledge and articulate all that is known (or, more accurately, thought to be known) and all that is not known about mixed pain. To inform the group's discussions, a Medline search for the Medical Subject Heading "mixed pain" was performed via PubMed. The search strategy encompassed clinical trial articles and reviews from January 1990 to the present. Clinically relevant articles were selected and reviewed. This paper summarizes the group's consensus on several key aspects of the mixed pain concept, to serve as a foundation for future attempts at generating a mechanistic and/or clinical definition of mixed pain. A definition would have important implications for the development of recommendations or guidelines for diagnosis and treatment of mixed pain.
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Pain and bone damage in rheumatoid arthritis: role of leukotriene B4.
Zheng, LX, Li, KX, Hong, FF, Yang, SL
Clinical and experimental rheumatology. 2019;(5):872-878
Abstract
Rheumatoid arthritis is a chronic autoimmune disease characterised by unbearable joint pain as well as bone and cartilage destruction. Although RA development is greatly controlled, the pain and bone damage failed to be relieved and managed. Leukotriene B4 (LTB4) has been proved to play an essential role in the induction of pain and bone damage. The nerve injury of RA can promote the production of LTB4, which act on their receptors, leading to the increased release of pro-inflammatory cytokines and ROS to reduce neuron viability and pain threshold. Moreover, LTB4-BLT1 activation can also increase intracellular calcium concentration and neuron excitability as well as NF-κB pathway activation, which further promote the production of MMP-9 and CXC3R-1. The mutual promotion between LTB4 and neutrophil accumulation accelerates the release of TNF-α and IL-β, which enhance both peripheral and central nerve system sensitisation. LTB4 also involve in TrpV1 channel activation and modulation of P2X3 receptor activation. All above mechanisms contribute to the development of RA pain. IL-23, cPLA2 and PI3K increase the production of CD11b+Gr1high myeloid subtype and calcium concentration, which promote the production of LTB4 and further accelerate IL-17 and TNF activation as well as calcium influx to conduce to osteoclastogenesis, resulting in aggregated bone damage. Our review is the first to conclude the signalling pathways and associated molecules in LTB4-induced pain and bone damage.
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Gadolinium use for interventional pain procedures: where we are and where we are heading.
Durbhakula, S, Cohen, SP
Regional anesthesia and pain medicine. 2019;(1):4-6
Abstract
In recent years as the use of interventional pain procedures has soared, so too has outside and internal scrutiny. This scrutiny includes agreater emphasis on weighing the risks and benefits of procedures, increased surveillance for adverse events, and cost containment strategies. In 2016, the first reports of gadolinium deposition in the central nervous system began to surface, though retention in other organ systems has been appreciated for over a decade. In this issue of Regional Anesthesia & Pain Medicine, Benzon et al. report a series of patients with document edhypersensitivity reactions to iodinated contrast medium who were inadvertently administered iodine-based contrast without adverse consequences. In this article, we discuss the epidemiology of contrast-mediated adverse effects, the mechanistic basis for hypersensitivity reactions, the risks and benefits of various approaches in the patient with a documented contrast hypersensitivity reaction, and risk mitigation strategies.
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P2X receptors and trigeminal neuralgia.
Li, JJ, Liu, ZX, Zhang, YL, Xue, GY
Neuroreport. 2019;(10):725-729
Abstract
There is currently no effective cure for trigeminal neuralgia (TN) - a relatively common disease that causes long-term pain in patients. Previous research has shown that ionotropic ATP signaling through excitatory and calcium-permeable P2X receptor channels plays a critical role in pathological pain generation and maintenance. In this paper, we review several hypotheses on the pathogenic mechanisms underlying TN. We further discuss pathways or agents that can target P2X expression in TN, thereby affecting pain induction and maintenance.
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Elagolix sodium for the treatment of women with moderate to severe endometriosis-associated pain.
Barra, F, Scala, C, Ferrero, S
Drugs of today (Barcelona, Spain : 1998). 2019;(4):237-246
Abstract
First-line medical therapies for treating pain associated with endometriosis mainly consist in combined oral contraceptives and progestins. However, some women, having persistence of symptoms, may require further therapeutic options. Among these, gonadotropin-releasing hormone (GnRH) agonists (GnRH-as) have been widely employed in the last 30 years, despite being characterized by an unfavorable safety profile. Currently, new alternative investigational options are being investigated to treat this benign chronic disease. GnRH antagonists (GnRH-ants) are innovative hormonal drugs that do not induce flare-up effects and present also a limited onset of hypoestrogenic symptoms; in fact, their pharmacological mechanism of action, which consists in pure antagonistic activity, differs from that of traditional GnRH-as. In July 2018, the U.S. Food and Drug Administration (FDA) approved elagolix sodium for the management of moderate to severe pain associated with endometriosis, after the drug showed promising efficacy and safety results in previous phase III trials. This monograph aims to provide a complete overview of the pharmacokinetics, clinical efficacy and safety of this GnRH-ant for treat¬ing patients with endometriosis.
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Glucosamine may be Effective in Treating Pain due to Knee Osteoarthritis.
Doshi, R, Ostrovsky, D
Explore (New York, N.Y.). 2019;(4):317-319
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Revisiting Tramadol: A Multi-Modal Agent for Pain Management.
Barakat, A
CNS drugs. 2019;(5):481-501
Abstract
Tramadol-an atypical opioid analgesic-has a unique pharmacokinetic and pharmacodynamic profile, with opioidergic, noradrenergic, and serotonergic actions. Tramadol has long been used as a well-tolerated alternative to other drugs in moderate pain because of its opioidergic and monoaminergic activities. However, cumulative evidence has been gathered over the last few years that supports other likely mechanisms and uses of tramadol in pain management. Tramadol has modulatory effects on several mediators involved in pain signaling, such as voltage-gated sodium ion channels, transient receptor potential V1 channels, glutamate receptors, α2-adrenoceptors, adenosine receptors, and mechanisms involving substance P, calcitonin gene-related peptide, prostaglandin E2, and proinflammatory cytokines. Tramadol also modifies the crosstalk between neuronal and non-neuronal cells in peripheral and central sites. Through these molecular effects, tramadol could modulate peripheral and central neuronal hyperexcitability. Given the broad spectrum of molecular targets, tramadol as a unimodal analgesic relieves a broad range of pain types, such as postoperative, low back, and neuropathic pain and that associated with labor, osteoarthritis, fibromyalgia, and cancer. Moreover, tramadol has anxiolytic, antidepressant, and anti-shivering activities that could improve pain management outcomes. The aim of this review was to address these issues in the context of maladaptive physiological and psychological processes that are associated with different pain types.
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Narrative review shows that the short-term use of ketorolac is safe and effective in the management of moderate-to-severe pain in children.
Marzuillo, P, Calligaris, L, Amoroso, S, Barbi, E
Acta paediatrica (Oslo, Norway : 1992). 2018;(4):560-567
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Abstract
UNLABELLED In June 2013, the European Medicine Agency recommended limiting codeine use in paediatric patients, creating a void in managing moderate pain. We reviewed the literature published in English (1985-June 2017) on the pharmacokinetic, pharmacodynamic and safety profile of ketorolac, a possible substitute for codeine and opioids, for treating moderate-to-severe pain. We found that gastrointestinal side effects were mainly reported with prolonged use, significant bleeding was reported in adenotonsillectomy, and adverse renal effects appeared to be limited to patients with specific coexisting risk factors. CONCLUSION The short-term use of ketorolac appears to be safe for children in many situations.
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Consensus recommendations for managing osteoarthritic pain with topical NSAIDs in Asia-Pacific.
Rafanan, BS, Valdecañas, BF, Lim, BP, Malairungsakul, A, Tassanawipas, W, Shiyi, C, Tse, LF, Luong, TK
Pain management. 2018;(2):115-128
Abstract
Osteoarthritis prevalence is expected to increase markedly in the Asia-Pacific region due to rapid population aging. Identifying effective and safe therapeutic options to manage osteoarthritic pain is viewed as a priority. The Asia-Pacific Experts on Topical Analgesics Advisory Board developed consensus statements for use of topical NSAIDs in musculoskeletal pain. Evidence supporting these statements in osteoarthritic pain was reviewed. Best available evidence indicates that topical NSAIDs have a moderate effect on relief of osteoarthritic pain, comparable to that of oral NSAIDs but with a better risk-to-benefit ratio. International clinical practice guidelines recommend topical NSAIDs on par with or ahead of oral NSAIDs for pain management in patients with knee and hand osteoarthritis, and as the first-line choice in persons aged ≥75 years.
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Is water exchange superior to water immersion for colonoscopy? A systematic review and meta-analysis.
Chen, Z, Li, Z, Yu, X, Wang, G
Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association. 2018;(5):259-267
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Abstract
BACKGROUND/AIMS: Recently, water exchange (WE) instead of water immersion (WI) for colonoscopy has been proposed to decrease pain and improve adenoma detection rate (ADR). This systematic review and meta-analysis is conducted to assess whether WE is superior to WI based on the published randomized controlled trials (RCTs). MATERIALS AND METHODS We searched studies from PubMed, Cochrane Central Register of Controlled Trials, EMBASE, and MEDLINE. Only RCTs were eligible for our study. The pooled risk ratios (RRs), pooled mean difference (MD), and pooled 95% confidence intervals (CIs) were calculated by using the fixed-effects model or random-effects model based on heterogeneity. RESULTS Five RCTs consisting of 2229 colonoscopies were included in this study. WE was associated with a significantly higher ADR than WI (RR = 1.18; CI = 1.05-1.32; P = 0.004), especially in right colon (RR = 1.31; CI = 1.07-1.61; P = 0.01). Compared with WI, WE was confirmed with lower pain score, higher Boston Bowel Preparation Scale score, but more infused water during insertion. There was no statistical difference between WE and WI in cecal intubation rate and the number of patients who had willingness to repeat the examination. Furthermore, both total procedure time and cecal intubation time in WE were significantly longer than that in WI (MD = 2.66; CI = 1.42-3.90; P < 0.0001; vs MD = 4.58; CI = 4.01-5.15; P < 0.0001). CONCLUSIONS This meta-analysis supports the hypothesis that WE is superior to WI in improving ADR, attenuating insertion pain and providing better bowel cleansing, but inferior in time and consumption of infused water consumption during insertion.