Browsing by Subject "pain"

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  • Kringel, Dario; Kaunisto, Mari A.; Lippmann, Catharina; Kalso, Eija; Lötsch, Jörn (2018)
    Background: Many gene variants modulate the individual perception of pain and possibly also its persistence. The limited selection of single functional variants is increasingly being replaced by analyses of the full coding and regulatory sequences of pain-relevant genes accessible by means of next generation sequencing (NGS). Methods: An NGS panel was created for a set of 77 human genes selected following different lines of evidence supporting their role in persisting pain. To address the role of these candidate genes, we established a sequencing assay based on a custom AmpliSeq (TM) panel to assess the exomic sequences in 72 subjects of Caucasian ethnicity. To identify the systems biology of the genes, the biological functions associated with these genes were assessed by means of a computational over-representation analysis. Results: Sequencing generated a median of 2.85 . 10(6) reads per run with a mean depth close to 200 reads, mean read length of 205 called bases and an average chip loading of 71%. A total of 3,185 genetic variants were called. A computational functional genomics analysis indicated that the proposed NGS gene panel covers biological processes identified previously as characterizing the functional genomics of persisting pain. Conclusion: Results of the NGS assay suggested that the produced nucleotide sequences are comparable to those earned with the classical Sanger sequencing technique. The assay is applicable for small to large-scale experimental setups to target the accessing of information about any nucleotide within the addressed genes in a study cohort.
  • Russo, Fabrizio; De Salvatore, Sergio; Ambrosio, Luca; Vadalà, Gianluca; Fontana, Luca; Papalia, Rocco; Rantanen, Jorma; Iavicoli, Sergio; Denaro, Vincenzo (2021)
    Low back pain (LBP) is currently the leading cause of disability worldwide and the mostcommon reason for workers’ compensation (WC) claims. Studies have demonstrated that receivingWC is associated with a negative prognosis following treatment for a vast range of health conditions.However, the impact of WC on outcomes after spine surgery is still controversial. The aim of thismeta-analysis was to systematically review the literature and analyze the impact of compensationstatus on outcomes after lumbar spine surgery. A systematic search was performed on Medline,Scopus, CINAHL, EMBASE and CENTRAL databases. The review included studies of patientsundergoing lumbar spine surgery in which compensation status was reported. Methodologicalquality was assessed through ROBINS-I and quality of evidence was estimated using the GRADErating. A total of 26 studies with a total of 2668 patients were included in the analysis. WC patientshad higher post-operative pain and disability, as well as lower satisfaction after surgery whencompared to those without WC. Furthermore, WC patients demonstrated to have a delayed return towork. According to our results, compensation status is associated with poor outcomes after lumbarspine surgery. Contextualizing post-operative outcomes in clinical and work-related domains helpsunderstand the multifactorial nature of the phenomenon.
  • Vainio, Sanna (Helsingfors universitet, 2019)
    Despite the long history of skin grafting, there is no standardized treatment for split-thickness skin graft donor sites. These sites cause a notable amount of pain and discomfort to the patients and open wounds also introduce a risk for infection. There is an extensive need for treatment options promoting the fastest and least painful healing possible while also being infection-free. The treatment of split-thickness skin graft donor sites is constantly studied and there is plenty of scientific literature available about this topic. In the theory section of this Master’s thesis, the structure of skin, the process of wound healing, skin grafting surgery and wound care products for split-thickness skin graft donor sites are briefly introduced. Additionally, the method of systematic review is described. In the empirical section, a systematic review is performed to compare animal- and non-animal-based wound care products in the treatment of split skin graft donor sites. The methodological quality of the included studies is reviewed. In the literature search, 3552 references were found. In this systematic review a total of 23 articles were included comprising of 21 comparative clinical studies and two previous literature reviews. Of the original studies, 20 reviewed healing, 14 infection and 17 pain of the split-thickness skin graft donor sites. Based on the results of the systematic review, animal-based wound care products might promote healing and reduce pain experienced by patients in the treatment of split-thickness skin graft donor sites when compared with non-animal-based wound care products. The results concerning infection were inconsistent. Generally, the reporting of the clinical original studies was not comprehensive enough for proper evaluation of methodological quality. Some defects, mostly in the blinding of the patients, study personnel and the assessors of outcomes, were also found. Moreover, the studies were heterogeneous in their definitions and measuring of the reported outcomes. Therefore, there is substantial uncertainty in the results of this systematic review. The systematic and transparent way of conducting the literature search, the review of the methodological quality and the reporting of the outcomes can be considered as a strength of this thesis. The main weakness is, that only one person performed the critical steps of this study, which might increase the risk of bias and reduce the repeatability of the study.
  • Graves, Meggan T.; Schneider, Liesel; Cox, Sherry; Caldwell, Marc; Krawczel, Peter; Lee, Amanda; Lear, Andrea (2020)
    The mitigation of pain associated with common management procedures is a rising concern among veterinarians, producers and consumers. Nonsteroidal anti-inflammatory drugs are vital compounds for this purpose due to their cost, convenience, and efficacy. A transdermal formulation of flunixin meglumine (FM) was approved for the treatment of pain in cattle; however, the efficacy has yet to be determined for small ruminants. The current study had two aims: 1) to determine the pharmacokinetics of transdermal flunixin meglumine (TD FM) in bucklings and 2) to evaluate pain mitigation by TD FM following castration. To evaluate pharmacokinetics, 12 male goats (mean age = 6 mo) received 2.2 mg/kg of FM IV (n = 6) or 3.3 mg/kg TD FM (n = 6). Plasma FM concentrations were measured. The mean C-max, T-max, and harmonic mean half-life for TD FM were 1.09 +/- 0.65 mu g/ mL, 5.50 +/- 2.95 h, and 7.16 +/- 2.06 h, respectively. To evaluate the efficacy of pain mitigation, 18 goats were randomly assigned to three treatment groups: 1) TD FM and castration (FM CAST) (n = 6); 2) transdermal placebo and castration (PL CAST) (n = 6); and 3) TD FM and sham castration (SHAM) (n = 6). Plasma samples were collected at 0, 12, 24, 36, 48, 72, and 96 h to assess cortisol and prostaglandin E-2 (PGE(2)). Daily dry matter intake (DMI) was recorded and body weight was measured at the beginning and end of the study. Thermography (IRT) images of the scrotum, as well as heart rate (HR), respiratory rate (RR), and rectal temperature, were taken twice daily. Separate mixed analysis of variance models were used to test the effects of treatment, time, and their interaction on mean body temperature, IRT, HR, and RR. Autoregressive covariance structure was utilized to account for repeated measures and individual goat DMI prior to the study was added as a covariate. There were no differences in vital parameters, IRT measurements, cortisol, or PGE(2) in animals receiving either TD FM or placebo following castration (P > 0.05). DMI had a treatment by hour interaction and was significantly higher in FM CAST and SHAM groups than the PL CAST group (P = 0.04). Goats in the SHAM group gained weight throughout the study, whereas goats in all other groups lost weight (P = 0.02). Results indicate that TD FM may mitigate pain as demonstrated by increased DMI; however, a single dose may not be sufficient to reduce physiological indicators of pain associated with castration in goats.
  • Mansnerus, Eeva (Helsingin yliopisto, 2020)
    Lasten hammashoidon tavoitteena on luoda pohja hyvälle suunterveydelle potilaan koko loppuelämäksi. Tämän saavuttamiseksi on tärkeää pitää suun alue terveenä. Lisäksi potilas on ohjattava käyttämään aktiivisesti hammashoidon palveluja. Hyvästä omahoidosta huolimatta, hammaslääkärin vastaanotolla joudutaan toisinaan tekemään toimenpiteitä, joihin liittyy kipua. Joskus tosin kipu voi myös olla syy hammashoitoon hakeutumiselle esimerkiksi, kun hammasydin tulehtuu hoitamattoman karieksen seurauksena. Lasten hammashoidossa toimenpiteitä, joihin liittyy kipua ovat muun muassa karioituneen hammaskudoksen poisto, endodonttiset ja parodontologiset hoidot, hampaan poistot sekä pienet kirurgiset toimenpiteet. Kivuliaat kokemukset voivat aiheuttaa pelkoa ja johtaa hammashoidon välttämiseen. Onkin ensisijaisen tärkeää, että lapsipotilaan kokema kipu otetaan huomioon ja sitä pyritään ehkäisemään ja lievittämään. Tutkielman tavoitteena on tehdä ajankohtainen kirjallisuuskatsaus kivunhallinnasta lasten hammashoidossa ja tätä kautta syventää tietämystä aiheesta. Tutkimus sisältää kolme eri aihealuetta. Ensin käsitellään kivun mekanismeja. Tämän jälkeen perehdytään siihen, kuinka lapsi kokee kivun hammashoidossa ja kuinka kipua voidaan arvioida. Lopuksi tutkielmassa käsitellään erilaisia lapsille sopivia kivunhallinnan keinoja. Tutkimusaineistona on käytetty aiheesta julkaistuja artikkeleita sekä osin myös alan ammattikirjallisuutta. Artikkeleita on haettu ensisijaisesti PubMedistä ja Ovid Medlinesta. Suomenkielisiä artikkeleita on haettu Medic-tietokannasta. Kipuaistimus välittyy periferiasta aivoihin kolmen eri tason hermosolujen kautta. Etenkin kivun aistimiseen liittyvän emotionaalisen puolen sekä kipua hermoston eri tasoilla moduloivien mekanismien takia kivun voimakkuuden arviointi voi olla ulkopuoliselle haastavaa. Apukeinoina tässä voidaan hyödyntää erilaisia kipumittareita. Lasten kivun ja siihen liittyvän pelon hallintaan on olemassa erilaisia vaihtoehtoja, joista sopivin pitäisi valita potilaskohtaisesti ja edessä olevan toimenpiteen mukaan. Pääpaino näissä menetelmissä on farmakologisissa valmisteissa: paikallispuudutteissa, kipulääkkeissä ja eriasteisissa sedaatioissa. Yhtä tärkeää on kuitenkin myös lapsen rauhoittaminen psykologisin keinoin.
  • Frondelius, Lilli; Hietaoja, Juha Kalevi; Pastell, Matti; Hänninen, Laura Talvikki; Anttila, Paula; Mononen, Jaakko (2018)
    This Research Communication describes the effect of post-operative pain and non-steroidal anti-inflammatory drug (NSAID) treatment on heart rate variability (HRV) of dairy cows. Postoperative pain in farm animals is often left untreated, and HRV could be a promising tool for assessing pain. The aim of this study was to assess if postoperative state after subcutaneous surgery affects HRV in dairy cows and to determine whether this could be modulated by NSAID. Nine cows were inserted with an implantable electrocardiograph logger. Cows were divided into the NSAID treatment group and the control group. The cows in the NSAID group had higher HRV than the control group, indicating a higher sympathetic activity in control animals, most likely due to untreated post-operative pain. Besides the ethical need for treating pain in production animals, ongoing pain has an adverse effect on animal productivity. Thus post-operative pain alleviation is recommended.
  • Lilius, T.; Kangas, E.; Niemi, M.; Rauhala, P.; Kalso, E. (2018)
    Background: Ketamine attenuates morphine tolerance by antagonising N-methyl-D-aspartate receptors. However, a pharmacokinetic interaction between morphine and ketamine has also been suggested. The interaction between oxycodone and ketamine is unclear. We studied the effects of ketamine and norketamine on the attenuation of morphine and oxycodone tolerance focusing on both the pharmacodynamic and pharmacokinetic interactions. Methods: Morphine 9.6 mg day(-1) or oxycodone 3.6 mg day(-1) was delivered to SpragueeDawley rats by subcutaneous pumps. Once tolerance had developed, the rats received subcutaneous injections of ketamine or norketamine. Tail-flick, hot-plate, and rotarod tests were performed. Drug concentrations were measured with high-performance liquid chromatographyetandem mass spectrometry. Results: Anti-nociceptive tolerance to morphine and oxycodone developed similarly by Day 6. Acute ketamine 10 mg kg(-1) and norketamine 30 mg kg(-1) attenuated morphine tolerance for 120 and 150 min, respectively, whereas in oxycodonetolerant rats the effect lasted only 60 min. Both ketamine and norketamine increased the brain and serum concentrations of morphine, and inhibited its metabolism to morphine-3-glucuronide, whereas oxycodone concentrations were not changed. Morphine, but not oxycodone, pretreatment increased the brain and serum concentrations of ketamine and norketamine. Ketamine, but not norketamine, significantly impaired the motor coordination. Conclusions: Ketamine and norketamine attenuated morphine tolerance more effectively than oxycodone tolerance. Ketamine and norketamine increased morphine, but not oxycodone brain concentrations, which may partly explain this difference. Norketamine is effective in attenuating morphine tolerance with minor effects on motor coordination. These results warrant pharmacokinetic studies in patients who are co-treated with ketamine and opioids.
  • Kiviranta, Elias (Helsingin yliopisto, 2021)
    Niin Suomessa kuin maailmallakin kivun on arvioitu liittyvän keskeisellä tavalla 40 prosenttiin terveyskeskuskäynneistä ja 60 prosenttiin päivystyskäynneistä. Suomessa kivun on arvioitu aiheuttavan vuosittain satojen miljoonien eurojen kustannukset yhteiskunnalle sekä suoraan (mm. sairauspäivärahat) että epäsuorasti (mm. menetetyt työvuodet). Tutkimme, saako terveydenhuollon henkilökunta Suomessa mielestään riittävästi kipukoulutusta, ja mitkä ovat vastaajien mielestä haasteellisimpia potilasryhmiä kivunhoidollisesta näkökulmasta katsottuna. Tutkimus toteutettiin jakamalla 100 kyselylomaketta Hyvinkään sairaalan päivystyksen henkilökunnalle. Lomakkeista palautui takaisin 49 kappaletta, ja vastaukset analysoitiin SPSS-tilastonkäsittelyohjelmalla. Vastaajista 82 prosenttia koki, että kipukoulutusta ei ole riittävästi, ja 92 prosenttia toivoi, että kipukoulutuksen määrää lisättäisiin. Työkokemuksen määrällä, tai aikaisemmin saadulla kipukoulutuksella ei ollut vaikutusta vastausten jakaumiin. Haastavimpina potilasryhminä pidettiin kipukroonikoita, lääkkeiden väärinkäyttäjiä ja muistisairauden tai muun syyn takia alentuneesti vuorovaikutuksessa olevia. Suosittelemme kipukoulutuksen määrän lisäämistä terveydenhuollon eri toimipisteissä, ja erityishuomion kiinnittämistä yllä mainittujen potilasryhmien hoidon erityispiirteisiin. (201 sanaa) MeSH: Pain, Treatment, Emergency Care
  • Kosonen, Henna (Helsingin yliopisto, 2021)
    Hormoni- ja kuparikierukka ovat luotettavia ja pitkäikäisiä ehkäisymenetelmiä, joita suositellaan ensisijaisena ehkäisymenetelmänä iästä ja synnyttäneisyydestä riippumatta. Hormonikierukkaa voidaan lisäksi käyttää terveydellisistä syistä. Kierukan asetukseen liittyvä kivun pelko saattaa kuitenkin estää potilasta valitsemasta kierukkaa. Tässä tutkimuksessa tutkitaan kivun kokemista kierukan asettamisen yhteydessä ja tekijöitä, jotka vaikuttavat kivun kokemiseen toimenpiteen aikana. Tutkimukseen osallistui 139 potilasta, joille lääketieteen opiskelija asetti hormoni- tai kuparikierukan. Potilailta kysyttiin ennen kierukan asettamista taustatietoja, toimenpiteen aikana koettu kipu eri vaiheissa VAS-janalla (visual analogue scale, 0-10 cm) ja lopuksi kokemus vastaanotosta. Saatu data käsiteltiin tilastotieteen menetelmin. Tilastollisen merkitsevyyden rajana pidettiin p-arvoa 0,05. Tutkimuksessa oletettu kipu oli keskimäärin 4,4 cm ja kivuliaimman vaiheen kipu oli keskimäärin 4,6 cm. Kivuliaimmat vaiheet olivat kohdun pituuden mittaus ja kierukan asetus. Kivun kokemista kierukan asettamisen aikana vähensi alatiesynnyttäneisyys, ikä 31-40-vuotta sekä vähäinen kivun ennakkoarvio, jännittäminen tai ahdistaminen. Kipulääkkeen käytöllä, kivunsiedolla, tilanteen pelkäämisellä, kierukkatyypillä, aiemmalla kierukkakokemuksella, käytetyllä ehkäisymenetelmällä, ajalla viimeisistä kuukautisista tai asettajan sukupuolella ei ollut vaikutusta koettuun kipuun. Suurin osa potilaista koki kierukan asettamisen siedettäväksi ja oli tyytyväisiä kierukan asetukseen. Tutkimuksessa ei saatu uutta kliinisesti merkittävää tietoa kierukan asetukseen liittyvästä kivusta tai siihen vaikuttavista tekijöistä.
  • Roinila, Markku (Springer, 2016)
    Logic, Argumentation & Reasoning
  • Fagerlund, Pi; Salmela, Jatta; Pietiläinen, Olli; Salonsalmi, Aino; Rahkonen, Ossi; Lallukka, Tea (Helsingin yliopisto, 2021)
    Abstract Background: Pain is known to be socio-economically patterned and associated with disability. However, knowledge is scarce concerning life-course socio-economic circumstances and pain among young adults. Our aim was to examine the associations of childhood and current socio-economic circumstances with acute pain and chronic pain with low and high disability levels among young Finnish municipal employees. Methods: We analyzed questionnaire data retrieved from the Young Helsinki Health Study (n=4683) covering 18–39-year-old employees of the City of Helsinki, Finland. We included a comprehensive set of indicators of childhood and current socio-economic circumstances and examined their associations with acute pain and with chronic pain with low and high disability levels. The level of chronic pain–related disability was assessed by the Chronic Pain Grade Questionnaire. Multinomial logistic regression analyses were conducted with stepwise adjustments for socio-demographic, socio-economic and health-related covariates. Results: Childhood and current socio-economic disadvantage were associated with acute and chronic pain, particularly with chronic pain with high disability level. The strongest associations after adjustments for covariates remained between chronic pain with high disability level and low education level (OR 3.38, 95% CI 2.18–5.24), manual occupation (OR 3.75, 95% CI 1.92–7.34) and experiencing frequent economic difficulties (OR 3.07, 95% CI 2.00–4.70). Conclusions: Pain is highly prevalent already among young employees and there is a socio-economic gradient in both pain chronicity and chronic pain–related disability. Life-course socio-economic determinants of pain should be considered in pain-preventing strategies and in clinical practice.
  • Bell, Rae Frances; Moreira, Vânia M.; Kalso, Eija; Yli-Kauhaluoma, Jari (2021)
    Liquorice has a long history of use in traditional Chinese, Ayurvedic and herbal medicine. The liquorice plant contains numerous bioactive compounds, including triterpenes, flavonoids and secondary metabolites, with glycyrrhizin being the main active compound. Liquorice constituents have been found to have anti-inflammatory, antioxidant, antiviral, anticancer, hepatoprotective and neuroprotective properties. In addition, they appear to have antidepressant actions and effects on morphine tolerance. Glycyrrhizin, its metabolite glycyrrhetic (glycyrrhetinic) acid and other liquorice-derived compounds such as isoflavonoids and trans-chalcones, exert potent anti-inflammatory effects via a wide range of mechanisms including high mobility group box 1 protein (HMGB1) inhibition, gap junction blockade and alpha(2A)-adrenoceptor antagonism. These properties, together with an increasing body of preclinical studies and a long history of use in herbal medicine, suggest that liquorice constituents may be useful for pain management. Glycyrrhizin is used widely in the confectionary, food and tobacco industries, but has documented adverse effects that may limit clinical use. Whether liquorice plant-derived compounds represent a novel class of analgesics is yet to be established. Having a host of bioactive compounds with a broad range of mechanisms of effect, liquorice is a plant that, in the future, may give rise to new therapies for pain.
  • Markkola, Anne (Helsingfors universitet, 2001)
    Tutkimuksessa pyrittiin löytämään menetelmiä, joilla voitaisiin luotettavasti mitata koiran nivelrikon aiheuttamaa kroonista kipua ja arvioida kipuhoidon tarvetta. Tutkimukseen valittiin 41 koiraa, joilla oli diagnosoitu lonkkaniveldysplasiasta johtuva nivelrikko ja jotka omistajien mukaan kärsivät kroonisesta kivusta. Koirista otettiin verinäytteet, joista analysoitiin adrenaliinin, noradrenaliinin, β-endorfiinin, antidiureettisen hormonin ja kortisolin pitoisuudet. Kaksi riippumatonta eläinlääkäriä arvioi videolta koirien liikkumista. Koirien lonkat röntgenkuvattiin. Omistajat täyttivät kyselykaavakkeen koiransa käyttäytymisestä ja mielialasta sekä arvioivat koiransa kokemaa kipua ja liikkumisvaikeuksia visuaalisilla analogiasteikoilla (kipujana ja liikkumisjana). Verinäytteiden kontrolliryhmään valittiin 22 omistajien mukaan tervettä koiraa, joilla ei ollut minkäänlaisia kipuoireita. Kyselykaavakkeen ja visuaalisten analogiasteikoiden kontrolliryhmään valittiin 24 omistajien mukaan tervettä ja kivutonta koiraa. Eläinlääkäreiden ja omistajien arviot koirien liikkumisvaikeuksista korreloivat positiivisesti keskenään. Adrenaliinin, antidiureettisen hormonin ja kortisolin pitoisuudet plasmassa olivat korkeammat kroonisesta kivusta kärsivillä koirilla kuin kontrolliryhmän koirilla, kun taas β-endorfiinipitoisuudet olivat korkeammat kontrolliryhmän koirilla. Koirilla, joilla röntgenologisesti todettiin luupiikkimuodostusta tai irtopaloja lonkkanivelessä, oli omistajien arvioiden mukaan enemmän liikkumisvaikeuksia mutta ei kipuja kuin muilla tutkimukseen osallistuneilla koirilla. Yksittäisen koirapotilaan kroonisen kivun arvioimiseen ei tutkimuksessa löydetty luotettavaa hormonaalista tai röntgenologista muuttujaa. Tutkimuksen perusteella eläinlääkäri voi arvioida koiran kipua ainoastaan sen liikkumisen perusteella. Omistajan kertomuksella koiran käyttäytymisestä, mielialasta ja liikkumisesta on nivelrikkokivun arvioinnissa keskeinen rooli. Eläinlääkärin tulee tulkita omistajan kertomuksesta koiran kivusta kertovat seikat ja/tai opettaa omistaja tulkitsemaan koiransa kipuoireita.
  • Valitalo, Pyry; Kokki, Merja; Ranta, Veli-Pekka; Olkkola, Klaus T.; Hooker, Andrew C.; Kokki, Hannu (2017)
    Purpose The aim of the current population pharmacokinetic study was to quantify oxycodone pharmacokinetics in children ranging from preterm neonates to children up to 7 years of age. Methods Data on intravenous or intramuscular oxycodone administration were obtained from three previously published studies (n = 119). The median [range] postmenstrual age of the subjects was 299 days [170 days-7.8 years]. A population pharmacokinetic model was built using 781 measurements of oxycodone plasma concentration. The model was used to simulate repeated intravenous oxycodone administration in four representative infants covering the age range from an extremely preterm neonate to 1-year old infant. Results The rapid maturation of oxycodone clearance was best described with combined allometric scaling and maturation function. Central and peripheral volumes of distribution were nonlinearly related to bodyweight. The simulations on repeated intravenous administration in virtual patients indicated that oxycodone plasma concentration can be kept between 10 and 50 ng/ml with a high probability when the maintenance dose is calculated using the typical clearance and the dose interval is 4 h. Conclustions Oxycodone clearance matures rapidly after birth, and between-subject variability is pronounced in neonates. The pharmacokinetic model developed may be used to evaluate different multiple dosing regimens, but the safety of repeated doses should be ensured.
  • FinnGen; Broberg, Martin; Karjalainen, Juha; Ollila, Hanna M. (2021)
    Study Objective: Insomnia has been linked to acute and chronic pain conditions; however, it is unclear whether such relationships are causal. Recently, a large number of genetic variants have been discovered for both insomnia and pain through genome-wide association studies (GWASs) providing a unique opportunity to examine the evidence for causal relationships through the use of the Mendelian randomization paradigm. Methods: To elucidate the causality between insomnia and pain, we performed bidirectional Mendelian randomization analysis in FinnGen, where clinically diagnosed ICD-10 categories of pain had been evaluated. In addition, we used measures of self-reported insomnia symptoms. We used endpoints for pain in the FinnGen Release 5 (R5) (N = 218,379), and a non-overlapping sample for insomnia (UK Biobank (UKBB) and 23andMe, N = 1,331,010 or UKBB alone N = 453,379). We assessed the robustness of results through conventional Mendelian randomization sensitivity analyses. Results: Genetic liability to insomnia symptoms increased the odds of reporting pain (odds ratio (OR) [95% confidence interval (CI)] = 1.47 [1.38-1.58], p = 4.12 x 10(-28)). Manifested pain had a small effect on increased risk for insomnia (OR [95% CI] = 1.04 [1.01-1.07], p < 0.05). Results were consistent in sensitivity analyses. Conclusions: Our findings support a bidirectional causal relationship between insomnia and pain. These data support a further clinical investigation into the utility of insomnia treatment as a strategy for pain management and vice versa.
  • Koroleva, Ksenia; Gafurov, Oleg; Guselnikova, Valeriia; Nurkhametovez, Dilyara; Giniatullina, Raisa; Sitdikova, Guzel; Mattila, Olli S.; Lindsberg, Perttu J.; Malm, Tarja Maarit; Giniatullin, Rashid (2019)
    Peripheral mechanisms of primary headaches such as a migraine remain unclear. Meningeal afferents surrounded by multiple mast cells have been suggested as a major source of migraine pain. Extracellular ATP released during migraine attacks is a likely candidate for activating meningeal afferents via neuronal P2X receptors. Recently, we showed that ATP also increased degranulation of resident meningeal mast cells (Nurkhametova et al., 2019). However, the contribution of ATP-induced mast cell degranulation in aggravating the migraine pain remains unknown. Here we explored the role of meningeal mast cells in the pro-nociceptive effects of extracellular ATP. The impact of mast cells on ATP mediated activation of peripheral branches of trigeminal nerves was measured electrophysiologically in the dura mater of adult wild type (WT) or mast cell deficient mice. We found that a spontaneous spiking activity in the meningeal afferents, at baseline level, did not differ in two groups. However, in WT mice, meningeal application of ATP dramatically (24.6-fold) increased nociceptive firing, peaking at frequencies around 10 Hz. In contrast, in mast cell deficient animals, ATP-induced excitation was significantly weaker (3.5-fold). Application of serotonin to meninges in WT induced strong spiking. Moreover, in WT mice, the 5-HT3 antagonist MDL-7222 inhibited not only serotonin but also the ATP induced nociceptive firing. Our data suggest that extracellular ATP activates nociceptive firing in meningeal trigeminal afferents via amplified degranulation of resident mast cells in addition to direct excitatory action on the nerve terminals. This highlights the importance of mast cell degranulation via extracellular ATP, in aggravating the migraine pain.
  • Pöyhönen, Suvi (Helsingfors universitet, 2017)
    Cortical stroke induces a chain of events that results in secondary injury in the ipsilateral thalamus. Inflammation is a key player in the delayed injury. Microglia, the resident innate immune cells of the brain, seem to have an important role in the initiation and maintenance of the inflammation. After infarct they are rapidly activated and start to proliferate and release proinflammatory cytokines. They may even phagocytose viable neurons, a phenomenon called "phagoptosis". Many studies, which have aimed at inhibition of the the detrimental function of microglia, suggest that inhibition of microglia might offer promising therapeutical targets. However, microglia are also involved in the resolution and the repair phase after infarct, which makes development of novel therapies challenging. The only approved treatment for ischemic stroke, a fibrinolytic agent, has a very narrow therapeutic time window. Thus, new treatments are urgently needed. Modulation of inflammation may offer a wider therapeutic time window. In this study, we investigated the effects of two potentially neurotrophic factors, CDNF (cerebral dopamine neurotrophic factor) and MANF (mesencephalic astrocyte-derived neurotrophic factor), as well as a specific vitronectin receptor blocker, cRGDfV, on the prevention of neuronal death in thalamus in a transient murine cortical stroke model. MANF and CDNF are proteins released during stress of the endoplasmic reticulum (ER). They have been shown to protect neurons during ER stress and to reduce the production of some proinflammatory mediators. The vitronectin receptor blocker has in vitro inhibited microglial phagoptosis. The treatments were administered as single injections to the thalamus 7 days after the stroke onset. CDNF and MANF alleviated functional deficits, but did not protect thalamic neurons from death or affect the accumulation of phagocytic microglia. cRGDfV neither enhanced functional outcome nor protected neurons from death. The mechanisms of action were not investigated. In addition, we investigated, whether the death of thalamic neurons in the cortical stroke results in sensitization to pain. Central post-stroke pain has been reported on stroke patients and it has been associated with the death or the disturbances in the function of thalamic neurons. However, in spite of significant reduction in the number of neurons in the ipsilateral thalamus and the increase in the accumulation of phagocytic microglia on day 30 after stroke, we did not observe any significant sensitization to pain caused by thermal or mechanical stimuli on days 3, 14 and 28 after stroke. In conclusion, transient ischemic cortical stroke doesn't seem to induce sensitization to pain. MANF and CDNF seem to alleviate functional deficiencies, but they do not protect thalamic neurons from delayed death.
  • Helminen, Eeva-Eerika; Arokoski, Jari P. A.; Selander, Tuomas A.; Sinikallio, Sanna H. (2020)
    Objective: To identify predictors of long-term pain and disability in knee osteoarthritis. Design: A longitudinal cohort study of five years. Setting: Primary care providers. Subjects: In all, 108 patients (mean age = 63.6 years, standard deviation (SD) = 7.2 years) with knee pain (> 40 mm on a 100 mm visual analogue scale in the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index pain scale) and radiographic grading (Kellgren-Lawrence: 2-4) of knee osteoarthritis who participated in a randomized controlled trial. Main measures: Disease-specific pain and functioning were assessed using the corresponding WOMAC subscales. Generic functioning was assessed by the RAND-36 subscales for function and physical and mental component summary scores. Possible baseline predictors for these outcomes were (1) demographic and disease-related variables and (2) psychological variables of mood (anxiety, depression), pain-related cognitions (pain self-efficacy, pain catastrophizing, kinesiophobia), and positive resource factors (life satisfaction, sense of coherence). Results: Multivariate linear mixed model analyses revealed that minimal anxiety at baseline predicted significantly better results for pain (WOMAC, P = 0.019) and function (WOMAC, P = 0.001, RAND-36 function P = 0.001). High pain self-efficacy predicted significantly better scores in RAND-36 function (P = 0.006), physical (P = 0.004) and mental (P = 0.001) component summaries. Pain catastrophizing predicted higher pain (P = 0.015), whereas fear of movement predicted poorer functioning in RAND-36 physical (P = 0.016) and mental (P = 0.009) component summaries. Those satisfied with life reported higher scores in RAND-36 function (P = 0.002) and mental component summary (P = 0.041). A low number of comorbidities predicted significantly better results in pain (WOMAC P = 0.019) and function (WOMAC P = 0.033, RAND-36 P = 0.009). Conclusion: Anxiety, pain-related cognitions, and psychological resources predict symptoms in knee osteoarthritis in the long term.