Protective effects of tuna meat oligopeptides (TMOP) supplementation on hyperuricemia and associated renal inflammation mediated by gut microbiota.

Recently, interest in using whole food-derived mixtures to alleviate chronic metabolic syndrome through potential synergistic interactions among different components is increasing. In this study, the effects and mechanisms of tuna meat oligopeptides (TMOP) on hyperuricemia and associated renal inflammation were investigated in mice. Dietary administration of TMOP alleviated hyperuricemia and renal inflammation phenotypes, reprogramed uric acid metabolism pathways, inhibited the activation of NLRP3 inflammasome and TLR4/MyD88/NF-κB signaling pathways, and suppressed the phosphorylation of p65-NF-κB. In addition, TMOP treatments repaired the intestinal epithelial barrier, reversed the gut microbiota dysbiosis and increased the production of short-chain fatty acids. Moreover, the antihyperuricemia effects of TMOP were transmissible by transplanting the fecal microbiota from TMOP-treated mice, indicating that the protective effects were at least partially mediated by the gut microbiota. Thus, for the first time, we clarify the potential effects of TMOP as a whole food derived ingredient on alleviating hyperuricemia and renal inflammation in mice, and additional efforts are needed to confirm the beneficial effects of TMOP on humans.

CaMKIIα Mediates the Effect of IL-17 To Promote Ongoing Spontaneous and Evoked Pain in Multiple Sclerosis.

Pain is a common and severe symptom in multiple sclerosis (MS), a chronic inflammatory and demyelinating disease of the CNS. The neurobiological mechanism underlying MS pain is poorly understood. In this study, we investigated the role of Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) in driving chronic pain in MS using a mouse experimental autoimmune encephalomyelitis (EAE) model. We found that spinal CaMKIIα activity was enhanced in EAE, correlating with the development of ongoing spontaneous pain and evoked hypersensitivity to mechanical and thermal stimuli. Prophylactic or acute administration of KN93, a CaMKIIα inhibitor, significantly reduced the clinical scores of EAE and attenuated mechanical allodynia and thermal hyperalgesia in EAE. siRNA targeting CaMKIIα reversed established mechanical and thermal hypersensitivity in EAE mice. Furthermore, CaMKIIαT286A point mutation mice showed significantly reduced EAE clinical scores, an absence of evoked pain, and ongoing spontaneous pain when compared with littermate wild-type mice. We found that IL-17 is responsible for inducing but not maintaining mechanical and thermal hyperalgesia that is mediated by CaMKIIα signaling in EAE. Together, these data implicate a critical role of CaMKIIα as a cellular mechanism for pain and neuropathy in multiple sclerosis and IL-17 may act upstream of CaMKIIα in the generation of pain.SIGNIFICANCE STATEMENT Pain is highly prevalent in patients with multiple sclerosis (MS), significantly reducing patients' quality of life. Using the experimental autoimmune encephalomyelitis (EAE) model, we were able to study not only evoked hyperalgesia, but also for the first time to demonstrate spontaneous pain that is also experienced by patients. Our study identified a role of spinal CaMKIIα in promoting and maintaining persistent ongoing spontaneous pain and evoked hyperalgesia pain in EAE. We further demonstrated that IL-17 contributes to persistent pain in EAE and functions as an upstream regulator of CaMKIIα signaling. These data for the first time implicated CaMKIIα and IL-17 as critical regulators of persistent pain in EAE, which may ultimately offer new therapeutic targets for mitigating pain in multiple sclerosis.

The AVPR1A Gene and Its Single Nucleotide Polymorphism rs10877969: A Literature Review of Associations with Health Conditions and Pain.

BACKGROUND: Pain is the quintessential symptom for individuals suffering from sickle cell disease (SCD). Although the degree of suffering and the cost of treatment are staggering, SCD continues to be grossly understudied, including a lack of data for pain-related genes and prevalence of polymorphisms in this population. This lack of data adds to the inadequacy of pain therapy in this population. Pain genetics investigators have recently examined allele frequencies of single-nucleotide polymorphisms from candidate genes in people who have SCD. One of the genes identified was the arginine vasopressin receptor 1A gene (AVPR1A) and its associated single-nucleotide polymorphism (SNP) rs10877969. Progress in explaining pain-related polymorphisms associated with SCD can be facilitated by understanding the literature. Aim/Design: The purpose of this literature review was to describe mechanisms of the polymorphic gene AVPR1A and the phenotypic variations associated with its SNPs relative to health conditions and pain. METHODS: Published studies were included if the research addressed AVPR1A and was a full article in a peer-reviewed journal, in the English language, a human or animal study, and published 2009 to present. Abstracts were included if they were in English and provided information not found in a full article. RESULTS: The results of this review revealed that AVPR1A is associated with behavioral phenotypes, which include pair bonding, autism spectrum disorder, musical aptitude, infidelity, altruism, monogamy, mating, substance abuse, and alcohol preference. In addition, there were associations with pain, stress pain by sex, and sickle cell pain. CONCLUSION: Summary of this literature could provide insights into future pain research of this SNP in people with SCD.

Differences in Sensory Pain, Expectation, and Satisfaction Reported by Outpatients with Cancer or Sickle Cell Disease.

BACKGROUND: Patients with sickle cell disease (SCD) report pain scores that appear greater than those reported in a meta-analysis for patients with cancer, but statistical comparisons of the pain scores from both populations have not been published. AIMS: The goal of the study described here was to compare pain outcomes reported by outpatients with cancer or SCD. DESIGN: Descriptive comparative study. SETTING: Outpatient oncology or sickle cell clinics. SUBJECTS: The participants were outpatients (N = 415) from three studies: (1) 106 patients with SCD, 93% African-American (referent group); (2) 140 patients with cancer, 90% Caucasian (race discordant); (3) 169 patients with cancer, 20% Caucasian, 65% African-American (race concordant). METHODS: Patients completed the PAINReportIt including pain location, quality, pattern, intensity, expectation, satisfaction, and demographic questions. Analyses included the χ2 test, analysis of variance, and regression. RESULTS: Outpatients with SCD reported more pain location sites than the race-discordant (p < .001) and race-concordant (p < .001) cancer groups; higher pain quality than the race-discordant (p < .001) and race-concordant (p < .001) groups; and greater pain pattern scores than the race-discordant (p < .001) and race-concordant (p < .001) groups. The race-concordant group reported higher worst pain intensity than the SCD (p < .001) and race-discordant (p = .002) groups. The three groups did not differ significantly on pain expectation (p = .06). Regarding satisfaction with pain level, there was a significant difference between the race-concordant and SCD (p = .006) groups, but not between the race-discordant and SCD (p = .12) groups or between the race-discordant and race-concordant (p = .49) groups. CONCLUSIONS: Outpatients with SCD reported three of four sensory pain parameters that were greater than those reported by outpatients with cancer. A better understanding of these differences is pertinent to improving pain outcomes.

Nociceptor beta II, delta, and epsilon isoforms of PKC differentially mediate paclitaxel-induced spontaneous and evoked pain.

As one of the most effective and frequently used chemotherapeutic agents, paclitaxel produces peripheral neuropathy (paclitaxel-induced peripheral neuropathy or PIPN) that negatively affects chemotherapy and persists after cancer therapy. The mechanisms underlying this dose-limiting side effect remain to be fully elucidated. This study aimed to investigate the role of nociceptor protein kinase C (PKC) isoforms in PIPN. Employing multiple complementary approaches, we have identified a subset of PKC isoforms, namely ßII, δ, and ϵ, were activated by paclitaxel in the isolated primary afferent sensory neurons. Persistent activation of PKCßII, PKCδ, and PKCϵ was also observed in the dorsal root ganglion neurons after chronic treatment with paclitaxel in a mouse model of PIPN. Isoform-selective inhibitors of PKCßII, PKCδ, and PKCϵ given intrathecally dose-dependently attenuated paclitaxel-induced mechanical allodynia and heat hyperalgesia. Surprisingly, spinal inhibition of PKCßII and PKCδ, but not PKCϵ, blocked the spontaneous pain induced by paclitaxel. These data suggest that a subset of nociceptor PKC isoforms differentially contribute to spontaneous and evoked pain in PIPN, although it is not clear whether PKCϵ in other regions regulates spontaneous pain in PIPN. The findings can potentially offer new selective targets for pharmacological intervention of PIPN.

Inhibition of CaMKIIα in the Central Nucleus of Amygdala Attenuates Fentanyl-Induced Hyperalgesia in Rats.

Opioid-induced hyperalgesia (OIH) is a less-studied phenomenon that has been reported in both preclinical and clinical studies. Although the underlying cause is not entirely understood, OIH is a real-life problem that affects millions of patients on a daily basis. Research has implicated the important contribution of Ca(2+)/calmodulin-dependent protein kinase IIα (CaMKIIα) to OIH at the level of spinal nociceptors. To expand our understanding of the entire brain circuitry driving OIH, in this study we investigated the role of CaMKIIα in the laterocapcular division of the central amygdala (CeLC), the conjunctive point between the spinal cord and rostro-ventral medulla. OIH was produced by repeated fentanyl administration in the rat. Correlating with the development of mechanical allodynia and thermal hyperalgesia, CaMKIIα activity was significantly elevated in the CeLC in OIH. In addition, the frequency and amplitude of spontaneous miniature excitatory postsynaptic currents (mEPSCs) in CeLC neurons were significantly increased in OIH. 2-[N-(2-hidroxyethyl)-N-(4-methoxy-benzenesulfonyl)]-amino-N-(4-chlorocinnamyl)-N-methylbenzylamine, a CaMKIIα inhibitor, dose dependently reversed sensory hypersensitivity, activation of CeLC CaMKIIα, and mEPSCs in OIH. Taken together, our data for the first time implicate a critical role of CeLC CaMKIIα in OIH.

Satisfied or not satisfied: pain experiences of patients with sickle cell disease.

AIMS: To examine the relationship between pain and satisfaction in patients with sickle cell disease. BACKGROUND: Frequency and severity of unrelieved sickle cell pain are positively associated with mortality. Yet, information is scarce on whether sickle cell patients are satisfied with their pain level. DESIGN: A cross-sectional, correlational analysis of baseline data from a randomized clinical trial. METHODS: A randomized sample of adult outpatients was recruited between February 2007-March 2011. Patients completed the PAINReportIt(®) , containing measures of pain, satisfaction and socio-demographics. We analysed data using Kendall's rank correlations, analysis of variance, Tukey-Kramer post hoc tests, Fisher's tests and proportional odds logistic regression. RESULTS: There were statistically significant correlations between pain outcomes and satisfaction with pain level, but average pain intensity more strongly discriminated groups based on satisfaction with pain level. Among pain variables bivariately associated with patient satisfaction with pain level, only pain expectation maintained its significant relationship with satisfaction with pain level when average pain intensity was controlled. A smaller percentage of our sickle cell patients reported moderate to severe pain intensity (28%) or high composite pain index (39%), while reporting being satisfied with pain their level than reported in earlier studies using different measures and populations (70-94%). CONCLUSION: Satisfaction with pain level was an unambiguous measure of patient satisfaction and a promising indicator of pain that did not show the paradoxical relationship between satisfaction and pain seen with past measures.

A randomized controlled pilot study feasibility of a tablet-based guided audio-visual relaxation intervention for reducing stress and pain in adults with sickle cell disease.

AIM: To test feasibility of a guided audio-visual relaxation intervention protocol for reducing stress and pain in adults with sickle cell disease. BACKGROUND: Sickle cell pain is inadequately controlled using opioids, necessitating further intervention such as guided relaxation to reduce stress and pain. DESIGN: Attention-control, randomized clinical feasibility pilot study with repeated measures. METHODS: Randomized to guided relaxation or control groups, all patients recruited between 2013-2014 during clinical visits, completed stress and pain measures via a Galaxy Internet-enabled Android tablet at the Baseline visit (pre/post intervention), 2-week posttest visit and also daily at home between the two visits. Experimental group patients were asked to use a guided relaxation intervention at the Baseline visit and at least once daily for 2 weeks. Control group patients engaged in a recorded sickle cell discussion at the Baseline visit. Data were analysed using linear regression with bootstrapping. RESULTS: At baseline, 27/28 of consented patients completed the study protocol. Group comparison showed that guided relaxation significantly reduced current stress and pain. At the 2-week posttest, 24/27 of patients completed the study, all of whom reported liking the study. Patients completed tablet-based measures on 71% of study days (69% in control group, 72% in experiment group). At the 2-week posttest, the experimental group had significantly lower composite pain index scores, but the two groups did not differ significantly on stress intensity. CONCLUSION: This study protocol appears feasible. The tablet-based guided relaxation intervention shows promise for reducing sickle cell pain and warrants a larger efficacy trial. TRIAL REGISTRATION: The ClinicalTrials.gov Identifier is: NCT02501447.

Safety and Utility of Quantitative Sensory Testing among Adults with Sickle Cell Disease: Indicators of Neuropathic Pain?

OBJECTIVES: Pain is the hallmark symptom of sickle cell disease (SCD), yet the types of pain that these patients experience, and the underlying mechanisms, have not been well characterized. The study purpose was to determine the safety and utility of a mechanical and thermal quantitative sensory testing (QST) protocol and the feasibility of utilizing neuropathic pain questionnaires among adults with SCD. METHODS: A convenience sample (N = 25, 18 women, mean age 38.5 ± 12.5 [20-58 years]) completed self-report pain and quality-of-life tools. Subjects also underwent testing with the TSA-II NeuroSensory Analyzer and calibrated von Frey microfilaments. RESULTS: We found that the QST protocol was safe and did not stimulate a SCD pain crisis. There was evidence of central sensitization (n = 15), peripheral sensitization (n = 1), a mix of central and peripheral sensitization (n = 8), or no sensitization (n = 1). The neuropathic pain self-report tools were feasible with evidence of construct validity; 40% of the subjects reported S-LANSS scores that were indicative of neuropathic pain and had evidence of central, peripheral or mixed sensitization. DISCUSSION: The QST protocol can be safely conducted in adults with SCD and provides evidence of central or peripheral sensitization, which is consistent with a neuropathic component to SCD pain. These findings are novel, warrant a larger confirmatory study, and indicate the need for normative QST data from African American adults and older adults.

Curcumin attenuates opioid tolerance and dependence by inhibiting Ca2+/calmodulin-dependent protein kinase II α activity.

Chronic use of opioid analgesics has been hindered by the development of opioid addiction and tolerance. We have reported that curcumin, a natural flavonoid from the rhizome of Curcuma longa, attenuated opioid tolerance, although the underlying mechanism remains unclear. In this study, we tested the hypothesis that curcumin may inhibit Ca(2+)/calmodulin-dependent protein kinase II α (CaMKIIα), a protein kinase that has been previously proposed to be critical for opioid tolerance and dependence. In this study, we used state-of-the-art polymeric formulation technology to produce poly(lactic-co-glycolic acid) (PLGA)-curcumin nanoparticles (nanocurcumin) to overcome the drug's poor solubility and bioavailability, which has made it extremely difficult for studying in vivo pharmacological actions of curcumin. We found that PLGA-curcumin nanoparticles reduced the dose requirement by 11- to 33-fold. Pretreatment with PLGA-curcumin (by mouth) prevented the development of opioid tolerance and dependence in a dose-dependent manner, with ED50 values of 3.9 and 3.2 mg/kg, respectively. PLGA-curcumin dose-dependently attenuated already-established opioid tolerance (ED50 = 12.6 mg/kg p.o.) and dependence (ED50 = 3.1 mg/kg p.o.). Curcumin or PLGA-curcumin did not produce antinociception by itself or affect morphine (1-10 mg/kg) antinociception. Moreover, we found that the behavioral effects of curcumin on opioid tolerance and dependence correlated with its inhibition of morphine-induced CaMKIIα activation in the brain. These results suggest that curcumin may attenuate opioid tolerance and dependence by suppressing CaMKIIα activity.

Dopamine D3 receptor Ser9Gly and catechol-o-methyltransferase Val158Met polymorphisms and acute pain in sickle cell disease.

BACKGROUND: Pain in sickle cell disease (SCD) is characterized by episodes of acute pain, primarily responsible for acute health care utilization, and persistent chronic pain. Pain severity and frequency vary significantly among patients with SCD. In this study, we investigated the possible contribution of monoamine gene polymorphisms to pain variation. METHODS: Adult subjects with SCD completed PAINReportIt, a computerized McGill Pain Questionnaire, from which we calculated the Composite Pain Index. Utilization data were obtained from the medical record and biweekly telephone calls for 12 months. Utilization is defined as admissions to the emergency department and/or the acute care center resulting from a sickle cell pain crisis. We performed genotyping for catechol-O-methyltransferase (COMT) Val158Met (rs4680) and dopamine D3 receptor (DRD3) Ser9Gly (rs6280) polymorphisms, which were analyzed for associations with pain phenotypes. RESULTS: Binary logistic models revealed that DRD3 Ser9Gly heterozygote patients were more likely not to have an acute pain crisis (odds ratio [OR] [95% confidence interval {CI}], 4.37 [1.39-22.89]; P = 0.020), which remained so when demographic variables were considered (OR [95% CI], 4.53 [1.41-28.58]; P = 0.016). COMT Val158Met Met allele showed lower probability for zero utilization (OR [95% CI], 0.32 [0.12-0.83]; P = 0.020) than the Val allele. In the negative binomial regression analysis, subjects with COMT Met/Met genotype had utilization incident rate ratio (95% CI) of 2.20 (1.21-3.99) over those with Val/Val (P = 0.010). CONCLUSIONS: These exploratory findings suggest that DRD3 Ser9Gly and COMT Val158Met may contribute to pain heterogeneity in SCD, as suggested by the different rates of acute pain crisis. Specifically, SCD patients with the DRD3 homozygote genotypes, COMT 158 Met allele or Met/Met genotype, are more likely to have acute care utilization, an indicator of acute pain. These results, however, will need to be further examined in future large prospective studies.

Gut microbiota dysbiosis alters chronic pain behaviors in a humanized transgenic mouse model of sickle cell disease.

ABSTRACT: Pain is the most common symptom experienced by patients with sickle cell disease (SCD) throughout their lives and is the main cause of hospitalization. Despite the progress that has been made towards understanding the disease pathophysiology, major gaps remain in the knowledge of SCD pain, the transition to chronic pain, and effective pain management. Recent evidence has demonstrated a vital role of gut microbiota in pathophysiological features of SCD. However, the role of gut microbiota in SCD pain is yet to be explored. We sought to evaluate the compositional differences in the gut microbiota of transgenic mice with SCD and nonsickle control mice and investigate the role of gut microbiota in SCD pain by using antibiotic-mediated gut microbiota depletion and fecal material transplantation (FMT). The antibiotic-mediated gut microbiota depletion did not affect evoked pain but significantly attenuated ongoing spontaneous pain in mice with SCD. Fecal material transplantation from mice with SCD to wild-type mice resulted in tactile allodynia (0.95 ± 0.17 g vs 0.08 ± 0.02 g, von Frey test, P < 0.001), heat hyperalgesia (15.10 ± 0.79 seconds vs 8.68 ± 1.17 seconds, radiant heat, P < 0.01), cold allodynia (2.75 ± 0.26 seconds vs 1.68 ± 0.08 seconds, dry ice test, P < 0.01), and anxiety-like behaviors (Elevated Plus Maze Test, Open Field Test). On the contrary, reshaping gut microbiota of mice with SCD with FMT from WT mice resulted in reduced tactile allodynia (0.05 ± 0.01 g vs 0.25 ± 0.03 g, P < 0.001), heat hyperalgesia (5.89 ± 0.67 seconds vs 12.25 ± 0.76 seconds, P < 0.001), and anxiety-like behaviors. These findings provide insights into the relationship between gut microbiota dysbiosis and pain in SCD, highlighting the importance of gut microbial communities that may serve as potential targets for novel pain interventions.

Orally administered nanocurcumin to attenuate morphine tolerance: comparison between negatively charged PLGA and partially and fully PEGylated nanoparticles.

We have formulated hydrophobic curcurmin [1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] into stable nanoparticle suspensions (nanocurcumin) to overcome its relatively low bioavailability, high rate of metabolism, and rapid elimination and clearance from the body. Employing the curcumin nanoformulations as the platform, we discovered that curcumin has the potential to alleviate morphine tolerance. The two types of stable polymeric nanoparticles, poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol)-b-poly(lactic acid) (PEG-b-PLA), and the hybrid of the two were generated using flash nanoprecipitation integrated with spray drying. The optimized formulations have high drug loading (>45%), small particles size with narrow distribution, and controlled surface properties. Mice behavioral studies (tail-flick and hot-plate tests) were conducted to verify the effects of nanocurcumin on attenuating morphine tolerance. Significant analgesia was observed in mice during both tail-flick and hot-plate tests using orally administered nanocurcumin following subcutaneous injections of morphine. However, unformulated curcumin at the same dose showed no effect. Compared with PEGylated nanocurcumin, negatively charged PLGA nanoparticles showed better functionality.

Candidate gene association study suggests potential role of dopamine beta-hydroxylase in pain heterogeneity in sickle cell disease.

Introduction: Pain is a lifelong companion of individuals with sickle cell disease (SCD) and has a severe impact on their quality of life. Both acute crisis pain and chronic non-crisis pain exhibit high variability between individuals, making it difficult to effectively manage sickle cell-related pain. We investigated the role of dopamine beta-hydroxylase (DBH) gene polymorphisms on pain variability in SCD. DBH is a key enzyme in the catecholamine biosynthesis pathway that catalyzes the conversion of dopamine to norepinephrine, both of which are known mediators of pain and pain-related behaviors. Methods: Acute crisis pain-related utilization and non-crisis chronic pain scores of 131 African Americans with SCD were obtained. Results and discussion: Association analyses revealed that the T allele of upstream variant rs1611115 and downstream variant rs129882 correlated with higher severity of chronic pain in an additive model. On the other hand, the A allele of missense variant rs5324 associated with lower risk of both acute crisis pain and chronic pain. Similarly, the C allele of intronic variant rs2797849 was associated with lower incidence of acute crisis pain in the additive model. In addition, tissue-specific eQTL revealed that the T allele of rs1611115 correlated with decreased expression of DBH in the frontal cortex and anterior cingulate cortex (GTEx), and decreased expression of DBH-AS1 in blood (eQTLGen). Bioinformatic approaches predicted that rs1611115 may be altering a transcription factor binding site, thereby, contributing to its potential effect. Taken together, findings from this study suggest that potential functional polymorphisms of DBH may modulate pain perception in SCD.

An alcohol dehydrogenase 7 gene polymorphism associates with both acute and chronic pain in sickle cell disease.

Introduction: As the most distressing complication of sickle cell disease (SCD), pain is marked by considerable heterogenicity. In this study we explored the potential association of alcohol dehydrogenase 7 gene (ADH7) polymorphism rs971074 with sickle cell pain. Methods: We analyzed clinical phenotypes and the rs971074 single-nucleotide polymorphism in ADH7 by MassARRAY-iPlex analysis in a cohort of SCD patients. Results: The synonymous rs971074 was significantly associated with both acute and chronic pain in SCD. Patients with the minor T allele(s) recorded significantly more crisis episodes and severe chronic pain symptoms. Conclusion: Our study has identified the rs971074 minor T allele as a genetic biomarker potentially influencing acute and chronic pain. These findings may ultimately help inform strategies to develop precision pain therapies in SCD.

Modified Akuamma Alkaloids with Increased Potency at the Mu-opioid Receptor.

Akuammine (1) and pseudoakuammigine (2) are indole alkaloids found in the seeds of the akuamma tree (Picralima nitida). Both alkaloids are weak agonists of the mu opioid receptor (µOR); however, they produce minimal effects in animal models of antinociception. To probe the interactions of 1 and 2 at the opioid receptors, we have prepared a collection of 22 semisynthetic derivatives. Evaluation of this collection at the µOR and kappa opioid receptor (κOR) revealed structural-activity relationship trends and derivatives with improved potency at the µOR. Most notably, the introduction of a phenethyl moiety to the N1 of 2 produces a 70-fold increase in potency and a 7-fold increase in selectivity for the µOR. The in vitro potency of this compound resulted in increased efficacy in the tail-flick and hot-plate assays of antinociception. The improved potency of these derivatives highlights the promise of exploring natural product scaffolds to probe the opioid receptors.

The McGill Pain Questionnaire as a multidimensional measure in people with cancer: an integrative review.

First published in 1975, the McGill Pain Questionnaire (MPQ) is an often-cited pain measure, but there have been no systematic reviews of the MPQ in cancer populations. Our objective was to evaluate the MPQ as a multidimensional measure of pain in people with cancer. A systematic search of research that used the MPQ in adults with cancer and published in English from 1975 to 2009 was conducted. Twenty-one articles retrieved through computerized searches and nine studies from manual searches met the criteria. Review of the 30 studies demonstrated that pain intensity (n = 29 studies) and pain quality (n = 27 studies) were measured more frequently than pain location, pattern, and behavior parameters. Measuring cancer pain using the MPQ provided insights about disease sites, magnitude of pain, and effectiveness of treatment and intervention. Additionally, the MPQ data informed speculations about pain mechanisms, emotional status, overall sensory pain experience, changes in pain over time, and alleviating and aggravating behaviors/factors. Findings supported the MPQ as an effective multidimensional measure with good stability, content, construct, and criterion validity and showed sensitivity to treatment or known-group effects. The MPQ is a valid, reliable, and sensitive multidimensional measure of cancer pain. Cancer pain is a subjective complex experience consisting of multiple dimensions, and measuring cancer pain with the MPQ may help clinicians to more fully understand whether those dimensions of cancer pain influence each other. As a result, clinicians can provide better and effective cancer pain management.

Correction: The gut microbiota mediates the protective effects of anserine supplementation on hyperuricaemia and associated renal inflammation.

Correction for 'The gut microbiota mediates the protective effects of anserine supplementation on hyperuricaemia and associated renal inflammation' by Jiaojiao Han et al., Food Funct., 2021, 12, 9030-9042, DOI: 10.1039/D1FO01884A.

Analysis of AVPR1A, thermal and pressure pain thresholds, and stress in sickle cell disease.

Aim: In patients with sickle cell disease (SCD), negative physical and emotional experiences result from intense chronic and acute pain episodes, but factors underlying these, and their interactions, are not well understood. The arginine vasopressin receptor 1a gene (AVPR1A) single nucleotide polymorphism rs10877969 has been previously associated with aspects of acute pain and stress related pain. In this study, we tested for associations between this SNP, thermal and pressure pain thresholds, clinical pain, and stress in people with SCD. Methods: 150 adults enrolled with SCD completed pain intensity measures (Average Pain Intensity, API) and the Perceived Stress Questionnaire (PSQ). Thermal and pressure pain threshold data were available from quantitative sensory testing (QST), and rs10877969 genotypes were obtained. Results: In models adjusted for age and gender, between rs10877969 genotypes, we observed no significant differences in thermal (cold, p = 0.66; heat, p = 0.91) and mechanical (pressure, p = 0.33) pain thresholds. The association of rs10877969 with API (p = 0.09) was borderline, but non-significant with PSQ (p = 0.51). The correlation between clinical pain and environmental stress was significant, r = 0.18, p = 0.024, however, the interaction of genotype and PSQ was not significant (p = 0.63). Conclusion: Clinical and experimental pain were not significantly associated with the rs10877969 genotype. The rs10877969 genotype did not moderate the correlation between environmental stress and clinical pain in this population. However, a trend toward a protective T allele effect on average pain rating in SCD warrants future exploration of this SNP/gene in SCD.