Publications by authors named "E A Kalso"

315 Publications

A Randomized, Sham-Controlled Trial of Repetitive Transcranial Magnetic Stimulation Targeting M1 and S2 in Central Poststroke Pain: A Pilot Trial.

Neuromodulation 2021 Aug 9. Epub 2021 Aug 9.

Department of Anaesthesiology, Intensive Care and Pain Medicine, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Objectives: Central poststroke pain (CPSP), a neuropathic pain condition, is difficult to treat. Repetitive transcranial magnetic stimulation (rTMS) targeted to the primary motor cortex (M1) can alleviate the condition, but not all patients respond. We aimed to assess a promising alternative rTMS target, the secondary somatosensory cortex (S2), for CPSP treatment.

Materials And Methods: This prospective, randomized, double-blind, Sham-controlled three-arm crossover trial assessed navigated rTMS (nrTMS) targeted to M1 and S2 (10 sessions, 5050 pulses per session at 10 Hz). Participants were evaluated for pain, depression, anxiety, health-related quality of life, upper limb function, and three plasticity-related gene polymorphisms including Dopamine D2 Receptor (DRD2). We monitored pain intensity and interference before and during stimulations, and at one month. A conditioned pain modulation test was performed using the cold pressor test. This assessed the efficacy of the descending inhibitory system, which may transmit TMS effects in pain control.

Results: We prescreened 73 patients, screened 29, and included 21, of whom 17 completed the trial. NrTMS targeted to S2 resulted in long-term (from baseline to one-month follow-up) pain intensity reduction of ≥30% in 18% (3/17) of participants. All stimulations showed a short-term effect on pain (17-20% pain relief), with no difference between M1, S2, or Sham stimulations, indicating a strong placebo effect. Only nrTMS targeted to S2 resulted in a significant long-term pain intensity reduction (15% pain relief). The cold pressor test reduced CPSP pain intensity significantly (p = 0.001), indicating functioning descending inhibitory controls. The homozygous DRD2 T/T genotype is associated with the M1 stimulation response.

Conclusions: S2 is a promising nrTMS target in the treatment of CPSP. The DRD2 T/T genotype might be a biomarker for M1 nrTMS response, but this needs confirmation from a larger study.
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http://dx.doi.org/10.1111/ner.13496DOI Listing
August 2021

Liquorice for pain?

Ther Adv Psychopharmacol 2021 16;11:20451253211024873. Epub 2021 Jul 16.

Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.

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 -chalcones, exert potent anti-inflammatory effects a wide range of mechanisms including high mobility group box 1 protein (HMGB1) inhibition, gap junction blockade and α-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.
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http://dx.doi.org/10.1177/20451253211024873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287643PMC
July 2021

Spared Nerve Injury Causes Sexually Dimorphic Mechanical Allodynia and Differential Gene Expression in Spinal Cords and Dorsal Root Ganglia in Rats.

Mol Neurobiol 2021 Jul 30. Epub 2021 Jul 30.

Department of Pharmacology, Faculty of Medicine, University of Helsinki, Haartmaninkatu 8 (Biomedicum 1), 00014, Helsinki, Finland.

Neuropathic pain is more prevalent in women. However, females are under-represented in animal experiments, and the mechanisms of sex differences remain inadequately understood. We used the spared nerve injury (SNI) model in rats to characterize sex differences in pain behaviour, unbiased RNA-Seq and proteomics to study the mechanisms. Male and female rats were subjected to SNI- and sham-surgery. Mechanical and cold allodynia were assessed. Ipsilateral lumbar dorsal root ganglia (DRG) and spinal cord (SC) segments were collected for RNA-seq analysis with DESeq2 on Day 7. Cerebrospinal fluid (CSF) samples for proteomic analysis and DRGs and SCs for analysis of IB-4 and CGRP, and IBA1 and GFAP, respectively, were collected on Day 21. Females developed stronger mechanical allodynia. There were no differences between the sexes in CGRP and IB-4 in the DRG or glial cell markers in the SC. No CSF protein showed change following SNI. DRG and SC showed abundant changes in gene expression. Sexually dimorphic responses were found in genes related to T-cells (cd28, ctla4, cd274, cd4, prf1), other immunological responses (dpp4, c5a, cxcr2 and il1b), neuronal transmission (hrh3, thbs4, chrna4 and pdyn), plasticity (atf3, c1qc and reg3b), and others (bhlhe22, mcpt1l, trpv6). We observed significantly stronger mechanical allodynia in females and numerous sexually dimorphic changes in gene expression following SNI in rats. Several genes have previously been linked to NP, while some are novel. Our results suggest gene targets for further studies in the development of new, possibly sex-specific, therapies for NP.
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http://dx.doi.org/10.1007/s12035-021-02447-1DOI Listing
July 2021

A search for modifying genetic factors in CHEK2:c.1100delC breast cancer patients.

Sci Rep 2021 Jul 20;11(1):14763. Epub 2021 Jul 20.

Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, Stockholm, Sweden.

The risk of breast cancer associated with CHEK2:c.1100delC is 2-threefold but higher in carriers with a family history of breast cancer than without, suggesting that other genetic loci in combination with CHEK2:c.1100delC confer an increased risk in a polygenic model. Part of the excess familial risk has been associated with common low-penetrance variants. This study aimed to identify genetic loci that modify CHEK2:c.1100delC-associated breast cancer risk by searching for candidate risk alleles that are overrepresented in CHEK2:c.1100delC carriers with breast cancer compared with controls. We performed whole-exome sequencing in 28 breast cancer cases with germline CHEK2:c.1100delC, 28 familial breast cancer cases and 70 controls. Candidate alleles were selected for validation in larger cohorts. One recessive synonymous variant, rs16897117, was suggested, but no overrepresentation of homozygous CHEK2:c.1100delC carriers was found in the following validation. Furthermore, 11 non-synonymous candidate alleles were suggested for further testing, but no significant difference in allele frequency could be detected in the validation in CHEK2:c.1100delC cases compared with familial breast cancer, sporadic breast cancer and controls. With this method, we found no support for a CHEK2:c.1100delC-specific genetic modifier. Further studies of CHEK2:c.1100delC genetic modifiers are warranted to improve risk assessment in clinical practice.
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http://dx.doi.org/10.1038/s41598-021-93926-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292481PMC
July 2021

International Association for the Study of Pain Presidential Task Force on Cannabis and Cannabinoid Analgesia: research agenda on the use of cannabinoids, cannabis, and cannabis-based medicines for pain management.

Pain 2021 07;162(Suppl 1):S117-S124

Pain Research, Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, United Kingdom.

Abstract: The President of the International Association for the Study of Pain established a task force on cannabis and cannabinoid analgesia to systematically examine the evidence on (1) analgesic pharmacology of cannabinoids and preclinical evidence on their efficacy in animal models of injury-related or pathological persistent pain; (2) the clinical efficacy of cannabis, cannabinoids, and cannabis-based medicines for pain; (3) harms related to long-term use of cannabinoids; as well as (4) societal issues and policy implications related to the use of these compounds for pain management. Here, we summarize key knowledge gaps identified in the task force outputs and propose a research agenda for generating high-quality evidence on the topic. The systematic assessment of preclinical and clinical literature identified gaps in rigor of study design and reporting across the translational spectrum. We provide recommendations to improve the quality, rigor, transparency, and reproducibility of preclinical and clinical research on cannabis and cannabinoids for pain, as well as for the conduct of systematic reviews on the topic. Gaps related to comprehensive understanding of the endocannabinoid system and cannabinoid pharmacology, including pharmacokinetics and drug formulation aspects, are discussed. We outline key areas where high-quality clinical trials with cannabinoids are needed. Remaining important questions about long-term and short-term safety of cannabis and cannabinoids are emphasized. Finally, regulatory, societal, and policy challenges associated with medicinal and nonmedicinal use of cannabis are highlighted, with recommendations for improving patient safety and reducing societal harms in the context of pain management.
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http://dx.doi.org/10.1097/j.pain.0000000000002266DOI Listing
July 2021
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