Signs and symptoms

  • Article
    | Open Access

    Spinal pain is a major clinical problem. Here the authors show that osteoclasts create porous area of endplates of the vertebrae and sensory innervation of porous endplates by Netrin-1 release from osteoclasts mediates PGE2-induced spinal hypersensitivity in mice.

    • Shuangfei Ni
    • , Zemin Ling
    • , Xiao Wang
    • , Yong Cao
    • , Tianding Wu
    • , Ruoxian Deng
    • , Janet L. Crane
    • , Richard Skolask
    • , Shadpour Demehril
    • , Gehua Zhen
    • , Amit Jain
    • , Panfeng Wu
    • , Dayu Pan
    • , Bo Hu
    • , Xiao Lyu
    • , Yusheng Li
    • , Hao Chen
    • , Huabin Qi
    • , Yun Guan
    • , Xinzhong Dong
    • , Mei Wan
    • , Xuenong Zou
    • , Hongbin Lu
    • , Jianzhong Hu
    •  & Xu Cao
  • Article
    | Open Access

    Alterations to the microbiome are now associated with various diseases. Here the authors analyze microbiomes from a large population based cohort and show positive correlations between abundance of Streptococcus spp. and osteoarthritis-related knee pain.

    • Cindy G. Boer
    • , Djawad Radjabzadeh
    • , Carolina Medina-Gomez
    • , Sanzhima Garmaeva
    • , Dieuwke Schiphof
    • , Pascal Arp
    • , Thomas Koet
    • , Alexander Kurilshikov
    • , Jingyuan Fu
    • , M. Arfan Ikram
    • , Sita Bierma-Zeinstra
    • , André G. Uitterlinden
    • , Robert Kraaij
    • , Alexandra Zhernakova
    •  & Joyce B. J. van Meurs
  • Article
    | Open Access

    Circular RNAs are non-coding RNAs that are enriched in the CNS, but their role in chronic pain is not known. Here the authors show that CircAnks1a in dorsal horn neurons contributes to pain-like hypersensitivity in a rodent model of neuropathic pain, via a VEGF mechanism.

    • Su-Bo Zhang
    • , Su-Yan Lin
    • , Meng Liu
    • , Cui-Cui Liu
    • , Huan-Huan Ding
    • , Yang Sun
    • , Chao Ma
    • , Rui-Xian Guo
    • , You-You Lv
    • , Shao-Ling Wu
    • , Ting Xu
    •  & Wen-Jun Xin
  • Article
    | Open Access

    Our experience of pain can be affected by our expectations about how much pain we will feel. Here, the authors show that both social information-driven expectations, and those based on personal experience, are both able to modulate pain, but by different neural pathways.

    • Leonie Koban
    • , Marieke Jepma
    • , Marina López-Solà
    •  & Tor D. Wager
  • Article
    | Open Access

    Gestational duration depends on both maternal and fetal genetic influences. Here, the authors perform a fetal genome-wide association meta-analysis and find that a locus on 2q13 is associated with pregnancy duration and further show that the lead SNP rs7594852 changes the binding properties of transcriptional repressor HIC1.

    • Xueping Liu
    • , Dorte Helenius
    • , Line Skotte
    • , Robin N. Beaumont
    • , Matthias Wielscher
    • , Frank Geller
    • , Julius Juodakis
    • , Anubha Mahajan
    • , Jonathan P. Bradfield
    • , Frederick T. J. Lin
    • , Suzanne Vogelezang
    • , Mariona Bustamante
    • , Tarunveer S. Ahluwalia
    • , Niina Pitkänen
    • , Carol A. Wang
    • , Jonas Bacelis
    • , Maria C. Borges
    • , Ge Zhang
    • , Bruce A. Bedell
    • , Robert M. Rossi
    • , Kristin Skogstrand
    • , Shouneng Peng
    • , Wesley K. Thompson
    • , Vivek Appadurai
    • , Debbie A. Lawlor
    • , Ilkka Kalliala
    • , Christine Power
    • , Mark I. McCarthy
    • , Heather A. Boyd
    • , Mary L. Marazita
    • , Hakon Hakonarson
    • , M. Geoffrey Hayes
    • , Denise M. Scholtens
    • , Fernando Rivadeneira
    • , Vincent W. V. Jaddoe
    • , Rebecca K. Vinding
    • , Hans Bisgaard
    • , Bridget A. Knight
    • , Katja Pahkala
    • , Olli Raitakari
    • , Øyvind Helgeland
    • , Stefan Johansson
    • , Pål R. Njølstad
    • , João Fadista
    • , Andrew J. Schork
    • , Ron Nudel
    • , Daniel E. Miller
    • , Xiaoting Chen
    • , Matthew T. Weirauch
    • , Preben Bo Mortensen
    • , Anders D. Børglum
    • , Merete Nordentoft
    • , Ole Mors
    • , Ke Hao
    • , Kelli K. Ryckman
    • , David M. Hougaard
    • , Leah C. Kottyan
    • , Craig E. Pennell
    • , Leo-Pekka Lyytikainen
    • , Klaus Bønnelykke
    • , Martine Vrijheid
    • , Janine F. Felix
    • , William L. Lowe Jr
    • , Struan F. A. Grant
    • , Elina Hyppönen
    • , Bo Jacobsson
    • , Marjo-Riitta Jarvelin
    • , Louis J. Muglia
    • , Jeffrey C. Murray
    • , Rachel M. Freathy
    • , Thomas M. Werge
    • , Mads Melbye
    • , Alfonso Buil
    •  & Bjarke Feenstra
  • Article
    | Open Access

    Fibrosis is a hallmark of several cardiac pathologies and its underlying mechanisms are still poorly defined. Here the authors show that macrophage hypoxia signaling following transverse aortic constriction in mice suppresses the activation of cardiac fibroblasts by secreting oncostatin M.

    • Hajime Abe
    • , Norihiko Takeda
    • , Takayuki Isagawa
    • , Hiroaki Semba
    • , Satoshi Nishimura
    • , Masaki Suimye Morioka
    • , Yu Nakagama
    • , Tatsuyuki Sato
    • , Katsura Soma
    • , Katsuhiro Koyama
    • , Masaki Wake
    • , Manami Katoh
    • , Masataka Asagiri
    • , Michael L. Neugent
    • , Jung-whan Kim
    • , Christian Stockmann
    • , Tomo Yonezawa
    • , Ryo Inuzuka
    • , Yasushi Hirota
    • , Koji Maemura
    • , Takeshi Yamashita
    • , Kinya Otsu
    • , Ichiro Manabe
    • , Ryozo Nagai
    •  & Issei Komuro
  • Article
    | Open Access

    Gamma oscillations in somatosensory areas in humans correlate with pain perception and pain stimulus intensity, but could also reflect cognitive processes such as attention. Here the authors provide evidence in mice that these oscillations causally contribute to pain perception.

    • Linette Liqi Tan
    • , Manfred Josef Oswald
    • , Céline Heinl
    • , Oscar Andrés Retana Romero
    • , Sanjeev Kumar Kaushalya
    • , Hannah Monyer
    •  & Rohini Kuner
  • Article
    | Open Access

    Pain is a complex phenomenon involving not just the perception of pain, but also autonomic and motor responses. Here, the authors show that these different dimensions of pain are associated with distinct patterns of neural responses to noxious stimuli as measured using EEG.

    • Laura Tiemann
    • , Vanessa D. Hohn
    • , Son Ta Dinh
    • , Elisabeth S. May
    • , Moritz M. Nickel
    • , Joachim Gross
    •  & Markus Ploner
  • Article
    | Open Access

    Ketamine is a short-acting analgesic that also has anti-depressant effects. Here the authors show in rat models of chronic pain that low-dose ketamine can induce an anti-aversive state that persists after the initial short term analgesia has ended.

    • Haocheng Zhou
    • , Qiaosheng Zhang
    • , Erik Martinez
    • , Jahrane Dale
    • , Sile Hu
    • , Eric Zhang
    • , Kevin Liu
    • , Dong Huang
    • , Guang Yang
    • , Zhe Chen
    •  & Jing Wang
  • Article
    | Open Access

    People vary in the extent to which they feel better after taking an inert, placebo, treatment, but the basis for individual placebo response is unclear. Here, the authors show how brain structural and functional variables, as well as personality traits, predict placebo response in those with chronic back pain.

    • Etienne Vachon-Presseau
    • , Sara E. Berger
    • , Taha B. Abdullah
    • , Lejian Huang
    • , Guillermo A. Cecchi
    • , James W. Griffith
    • , Thomas J. Schnitzer
    •  & A. Vania Apkarian
  • Article
    | Open Access

    Systemic chronic hypoxia is a feature of many diseases and may influence the communication between bone marrow and gut microbiota. Here, the authors show that chronic hypoxia predisposes bone marrow stem cells to premature senescence, which may be due to gut dysbiosis and gut microbiota-derived d-galactose accumulation.

    • Junyue Xing
    • , Yongquan Ying
    • , Chenxi Mao
    • , Yiwei Liu
    • , Tingting Wang
    • , Qian Zhao
    • , Xiaoling Zhang
    • , Fuxia Yan
    •  & Hao Zhang
  • Article
    | Open Access

    It is known that descending facilitation of spinal responses may contribute to chronic pain, however many studies have focussed on brainstem mechanisms. Here the authors show that stimulation of the anterior cingulate cortex increases excitatory transmission in the dorsal horn, and that this may be via a direct pathway independent of the brainstem.

    • Tao Chen
    • , Wataru Taniguchi
    • , Qi-Yu Chen
    • , Hidetoshi Tozaki-Saitoh
    • , Qian Song
    • , Ren-Hao Liu
    • , Kohei Koga
    • , Tsuyoshi Matsuda
    • , Yae Kaito-Sugimura
    • , Jian Wang
    • , Zhi-Hua Li
    • , Ya-Cheng Lu
    • , Kazuhide Inoue
    • , Makoto Tsuda
    • , Yun-Qing Li
    • , Terumasa Nakatsuka
    •  & Min Zhuo
  • Article
    | Open Access

    There are several classes of sensory neuron that contribute to pain states. Here, the authors demonstrate that TrkB+ sensory neurons detect light touch under normal conditions in mice but contribute to hypersensitivity in models of chronic pain, and that ligand-guided laser ablation of TrkB+ sensory neurons in the mouse skin attenuates this hypersensitivity.

    • Rahul Dhandapani
    • , Cynthia Mary Arokiaraj
    • , Francisco J. Taberner
    • , Paola Pacifico
    • , Sruthi Raja
    • , Linda Nocchi
    • , Carla Portulano
    • , Federica Franciosa
    • , Mariano Maffei
    • , Ahmad Fawzi Hussain
    • , Fernanda de Castro Reis
    • , Luc Reymond
    • , Emerald Perlas
    • , Simone Garcovich
    • , Stefan Barth
    • , Kai Johnsson
    • , Stefan G. Lechner
    •  & Paul A. Heppenstall
  • Article
    | Open Access

    SUMOylation is a post translational modification. Here the authors show that TRPV1, which conveys thermal nociception, is SUMOylated in DRGs in inflammatory conditions and contributes to pain behavior in mice.

    • Yan Wang
    • , Yingwei Gao
    • , Quan Tian
    • , Qi Deng
    • , Yangbo Wang
    • , Tian Zhou
    • , Qiang Liu
    • , Kaidi Mei
    • , Yingping Wang
    • , Huiqing Liu
    • , Ruining Ma
    • , Yuqiang Ding
    • , Weifang Rong
    • , Jinke Cheng
    • , Jing Yao
    • , Tian-Le Xu
    • , Michael X. Zhu
    •  & Yong Li
  • Article
    | Open Access

    Sensitisation of dorsal root ganglia neurons contributes to neuropathic pain. Here the authors demonstrate the cytokine FL contributes to sensitisation of DRGs via its receptor FLT3 expressed on neurons, and identify a novel FLT3 inhibitor that attenuates neuropathic pain in mice.

    • Cyril Rivat
    • , Chamroeun Sar
    • , Ilana Mechaly
    • , Jean-Philippe Leyris
    • , Lucie Diouloufet
    • , Corinne Sonrier
    • , Yann Philipson
    • , Olivier Lucas
    • , Sylvie Mallié
    • , Antoine Jouvenel
    • , Adrien Tassou
    • , Henri Haton
    • , Stéphanie Venteo
    • , Jean-Philippe Pin
    • , Eric Trinquet
    • , Fabienne Charrier-Savournin
    • , Alexandre Mezghrani
    • , Willy Joly
    • , Julie Mion
    • , Martine Schmitt
    • , Alexandre Pattyn
    • , Frédéric Marmigère
    • , Pierre Sokoloff
    • , Patrick Carroll
    • , Didier Rognan
    •  & Jean Valmier
  • Article
    | Open Access

    Bacterial infection can cause pain but the underlying mechanism is unclear. This study shows pain induced in mice by methicillin-resistant Staphylococcus aureus infection is mediated by bacterial pore-forming toxins, and a sodium channel blocker QX-314 can alleviate infection-associated pain.

    • Kimbria J. Blake
    • , Pankaj Baral
    • , Tiphaine Voisin
    • , Ashira Lubkin
    • , Felipe Almeida Pinho-Ribeiro
    • , Kelsey L. Adams
    • , David P. Roberson
    • , Yuxin C. Ma
    • , Michael Otto
    • , Clifford J. Woolf
    • , Victor J. Torres
    •  & Isaac M. Chiu
  • Article
    | Open Access

    Following peripheral nerve injury, influx of immune cells to the site may contribute to the development of chronic pain. Here the authors show that TRPA1 is expressed on Schwann cells and contributes to immune cell influx in a mouse model of neuropathic pain.

    • Francesco De Logu
    • , Romina Nassini
    • , Serena Materazzi
    • , Muryel Carvalho Gonçalves
    • , Daniele Nosi
    • , Duccio Rossi Degl’Innocenti
    • , Ilaria M. Marone
    • , Juliano Ferreira
    • , Simone Li Puma
    • , Silvia Benemei
    • , Gabriela Trevisan
    • , Daniel Souza Monteiro de Araújo
    • , Riccardo Patacchini
    • , Nigel W. Bunnett
    •  & Pierangelo Geppetti
  • Article
    | Open Access

    Exosomes are known to contain microRNAs (miRs). Here the authors show that dorsal root ganglion neurons release exosomes containing miR-21-5p, which contributes to inflammatory cell recruitment following peripheral nerve injury.

    • Raffaele Simeoli
    • , Karli Montague
    • , Hefin R. Jones
    • , Laura Castaldi
    • , David Chambers
    • , Jayne H. Kelleher
    • , Valentina Vacca
    • , Thomas Pitcher
    • , John Grist
    • , Hadil Al-Ahdal
    • , Liang-Fong Wong
    • , Mauro Perretti
    • , Johnathan Lai
    • , Peter Mouritzen
    • , Paul Heppenstall
    •  & Marzia Malcangio
  • Article
    | Open Access

    Hyperoxia contributes to lung injury in bronchopulmonary dysplasia. The authors show that hyperoxia increases miR-34a expression in human neonates and in mouse models, and that pathology is ameliorated by miR-34a inhibition or by administration of its target angiopoietin-1

    • Mansoor Syed
    • , Pragnya Das
    • , Aishwarya Pawar
    • , Zubair H. Aghai
    • , Anu Kaskinen
    • , Zhen W. Zhuang
    • , Namasivayam Ambalavanan
    • , Gloria Pryhuber
    • , Sture Andersson
    •  & Vineet Bhandari
  • Article
    | Open Access

    Various forms of preconditioning can prevent ischemic-reperfusion injury after myocardial infarction. Here, the authors show that in mice, the presence of chronic neuropathic pain can have a cardioprotective effect, and that this is dependent on neural activation in the paraventricular thalamus.

    • Yi-Fen Cheng
    • , Ya-Ting Chang
    • , Wei-Hsin Chen
    • , Hsi-Chien Shih
    • , Yen-Hui Chen
    • , Bai-Chuang Shyu
    •  & Chien-Chang Chen
  • Article
    | Open Access

    Semaphorins and their receptors are involved in neurodevelopment, but their functions in the adult nervous system are not fully understood. This study finds that semaphorin 4C and its receptor Plexin B are expressed in sensory neurons and are pronociceptive in a mouse model of inflammatory pain.

    • Eszter Paldy
    • , Manuela Simonetti
    • , Thomas Worzfeld
    • , Kiran Kumar Bali
    • , Lucas Vicuña
    • , Stefan Offermanns
    •  & Rohini Kuner
  • Article
    | Open Access

    Removal of senescent cells rejuvenates lungs of aged mice. Here the authors show that elimination of senescent cells using either genetic or pharmacological means improves lung function and physical health in a mouse model of idiopathic pulmonary fibrosis (IPF), suggesting potential therapy for treatment of human IPF.

    • Marissa J. Schafer
    • , Thomas A. White
    • , Koji Iijima
    • , Andrew J. Haak
    • , Giovanni Ligresti
    • , Elizabeth J. Atkinson
    • , Ann L. Oberg
    • , Jodie Birch
    • , Hanna Salmonowicz
    • , Yi Zhu
    • , Daniel L. Mazula
    • , Robert W. Brooks
    • , Heike Fuhrmann-Stroissnigg
    • , Tamar Pirtskhalava
    • , Y. S. Prakash
    • , Tamara Tchkonia
    • , Paul D. Robbins
    • , Marie Christine Aubry
    • , João F. Passos
    • , James L. Kirkland
    • , Daniel J. Tschumperlin
    • , Hirohito Kita
    •  & Nathan K. LeBrasseur
  • Article
    | Open Access

    Pain is affected by cerebral processes in addition to afferent nociceptive input. Here the authors develop an fMRI-based signature that predicts pain independent of the intensity of nociceptive signals and mediates the pain-modulating effects of several cognitive interventions.

    • Choong-Wan Woo
    • , Liane Schmidt
    • , Anjali Krishnan
    • , Marieke Jepma
    • , Mathieu Roy
    • , Martin A. Lindquist
    • , Lauren Y. Atlas
    •  & Tor D. Wager
  • Article
    | Open Access

    Patients with diabetes often have delayed wound healing, associated with excessive inflammation. Here the authors report that REG3A inhibits TLR3-driven inflammation in skin wounds, and show that REG3A is reduced in models of diabetes, which exacerbates inflammation in diabetic wounds.

    • Yelin Wu
    • , Yanchun Quan
    • , Yuanqi Liu
    • , Keiwei Liu
    • , Hongquan Li
    • , Ziwei Jiang
    • , Tian Zhang
    • , Hu Lei
    • , Katherine A. Radek
    • , Dongqing Li
    • , Zhenhua Wang
    • , Jilong Lu
    • , Wang Wang
    • , Shizhao Ji
    • , Zhaofan Xia
    •  & Yuping Lai
  • Article
    | Open Access

    TRPV1 channels are known to mediate pathological pain and itch. Here, the authors find a naturally occurring fatty acid, oleic acid, acts as a TRPV1 antagonist and can modulate capsaicin and histamine-mediated pain and itch response in mouse models.

    • Sara L. Morales-Lázaro
    • , Itzel Llorente
    • , Félix Sierra-Ramírez
    • , Ana E. López-Romero
    • , Miguel Ortíz-Rentería
    • , Barbara Serrano-Flores
    • , Sidney A. Simon
    • , León D. Islas
    •  & Tamara Rosenbaum
  • Article
    | Open Access

    Purinergic receptor activation by extracellular ATP in the dorsal horn contributes to neuropathic pain, but which cell types release ATP in this context is not known. The authors show in a mouse model of neuropathic pain that ATP is released by dorsal horn neurons, a process requiring the vesicular nucleotide transporter, VNUT.

    • Takahiro Masuda
    • , Yui Ozono
    • , Satsuki Mikuriya
    • , Yuta Kohro
    • , Hidetoshi Tozaki-Saitoh
    • , Ken Iwatsuki
    • , Hisayuki Uneyama
    • , Reiko Ichikawa
    • , Michael W. Salter
    • , Makoto Tsuda
    •  & Kazuhide Inoue
  • Article
    | Open Access

    The presence of the signalling lipid Sphingosine 1-phosphate (S1P) in erythrocytes has unclear physiological implications. Here the authors show that the S1P-generating enzyme Sphingosine kinase type 1 and its product S1P play an important role in the red blood cell adaptation to hypoxic environments in mice and humans.

    • Kaiqi Sun
    • , Yujin Zhang
    • , Angelo D’Alessandro
    • , Travis Nemkov
    • , Anren Song
    • , Hongyu Wu
    • , Hong Liu
    • , Morayo Adebiyi
    • , Aji Huang
    • , Yuan E. Wen
    • , Mikhail V. Bogdanov
    • , Alejandro Vila
    • , John O’Brien
    • , Rodney E. Kellems
    • , William Dowhan
    • , Andrew W. Subudhi
    • , Sonja Jameson-Van Houten
    • , Colleen G. Julian
    • , Andrew T. Lovering
    • , Martin Safo
    • , Kirk C. Hansen
    • , Robert C. Roach
    •  & Yang Xia
  • Article
    | Open Access

    Microglia and monocytes contribute to neuropathic pain states, but the precise role of the two cell types is not clear. Here Peng et al.use temporally controlled ablation of monocytes and microglia in mice to show that these cells work together to initiate neuropathic-pain like behaviour, but are less important in the maintenance phase.

    • Jiyun Peng
    • , Nan Gu
    • , Lijun Zhou
    • , Ukpong B Eyo
    • , Madhuvika Murugan
    • , Wen-Biao Gan
    •  & Long-Jun Wu
  • Article
    | Open Access

    The etiology of focal cortical dysplasia (FCD) is not fully understood. Here authors generate an mTORC1 overactivation mouse model that recapitulates hallmarks of type II FCDs, including spontaneous seizures, and suggest that neuronal defects, rather than macrostructural changes, lead to seizures.

    • Lawrence S. Hsieh
    • , John H. Wen
    • , Kumiko Claycomb
    • , Yuegao Huang
    • , Felicia A. Harrsch
    • , Janice R. Naegele
    • , Fahmeed Hyder
    • , Gordon F. Buchanan
    •  & Angelique Bordey
  • Article
    | Open Access

    Long-term use of opioids can lead to a paradoxical increase in pain sensitivity. Here, Hayashi et al. link activation of potassium channels on microglia with morphine-induced hyperalgesia and anti-nociceptive tolerance in mice.

    • Yoshinori Hayashi
    • , Saori Morinaga
    • , Jing Zhang
    • , Yasushi Satoh
    • , Andrea L. Meredith
    • , Takahiro Nakata
    • , Zhou Wu
    • , Shinichi Kohsaka
    • , Kazuhide Inoue
    •  & Hiroshi Nakanishi
  • Article
    | Open Access

    Hypoxia promotes tumour aggressiveness and resistance of cancers to oncological treatment. Here, the authors show that caveolin-1 can down-regulate global membrane protein endocytosis in hypoxic cells with potential implications for targeting the hypoxic 3microenvironment of aggressive tumours.

    • E. Bourseau-Guilmain
    • , J. A. Menard
    • , E. Lindqvist
    • , V. Indira Chandran
    • , H. C. Christianson
    • , M. Cerezo Magaña
    • , J. Lidfeldt
    • , G. Marko-Varga
    • , C. Welinder
    •  & M. Belting
  • Article
    | Open Access

    Anterior insula (AI) and medial anterior cingulate cortex (mACC) are activated by self and vicarious pain, disgust and fairness, yet the overlap of these representations are not known. Here the authors provide evidence for shared neural codes in the left AI and mACC and distinct codes in the right AI.

    • Corrado Corradi-Dell’Acqua
    • , Anita Tusche
    • , Patrik Vuilleumier
    •  & Tania Singer
  • Article
    | Open Access

    A mutation in the sodium channel Nav1.9 has been identified in a family and shown to associate with cold-aggravated pain. Here, the authors characterize the electrophysiological consequences of this mutation and propose a mechanism for the pain that the individuals experience.

    • Enrico Leipold
    • , Andrea Hanson-Kahn
    • , Miya Frick
    • , Ping Gong
    • , Jonathan A. Bernstein
    • , Martin Voigt
    • , Istvan Katona
    • , R. Oliver Goral
    • , Janine Altmüller
    • , Peter Nürnberg
    • , Joachim Weis
    • , Christian A. Hübner
    • , Stefan H. Heinemann
    •  & Ingo Kurth
  • Article
    | Open Access

    Nav1.7 channels are known to regulate pain perception in humans and mice. Here, the authors provide evidence that Nav1.7 deletion leads to transcriptional upregulation of opioid peptides in sensory neurons, and that treatment with the opioid blocker naloxone helps reverse analgesia in mice and human Nav1.7 nulls.

    • Michael S. Minett
    • , Vanessa Pereira
    • , Shafaq Sikandar
    • , Ayako Matsuyama
    • , Stéphane Lolignier
    • , Alexandros H. Kanellopoulos
    • , Flavia Mancini
    • , Gian D. Iannetti
    • , Yury D. Bogdanov
    • , Sonia Santana-Varela
    • , Queensta Millet
    • , Giorgios Baskozos
    • , Raymond MacAllister
    • , James J. Cox
    • , Jing Zhao
    •  & John N. Wood
  • Article
    | Open Access

    The development of asthma following eczema is known as the atopic march. Here the authors conduct a GWAS on affected children and identify two novel loci associated with the disease phenotype.

    • Ingo Marenholz
    • , Jorge Esparza-Gordillo
    • , Franz Rüschendorf
    • , Anja Bauerfeind
    • , David P. Strachan
    • , Ben D. Spycher
    • , Hansjörg Baurecht
    • , Patricia Margaritte-Jeannin
    • , Annika Sääf
    • , Marjan Kerkhof
    • , Markus Ege
    • , Svetlana Baltic
    • , Melanie C. Matheson
    • , Jin Li
    • , Sven Michel
    • , Wei Q. Ang
    • , Wendy McArdle
    • , Andreas Arnold
    • , Georg Homuth
    • , Florence Demenais
    • , Emmanuelle Bouzigon
    • , Cilla Söderhäll
    • , Göran Pershagen
    • , Johan C. de Jongste
    • , Dirkje S. Postma
    • , Charlotte Braun-Fahrländer
    • , Elisabeth Horak
    • , Ludmila M. Ogorodova
    • , Valery P. Puzyrev
    • , Elena Yu Bragina
    • , Thomas J. Hudson
    • , Charles Morin
    • , David L. Duffy
    • , Guy B. Marks
    • , Colin F. Robertson
    • , Grant W. Montgomery
    • , Bill Musk
    • , Philip J. Thompson
    • , Nicholas G. Martin
    • , Alan James
    • , Patrick Sleiman
    • , Elina Toskala
    • , Elke Rodriguez
    • , Regina Fölster-Holst
    • , Andre Franke
    • , Wolfgang Lieb
    • , Christian Gieger
    • , Andrea Heinzmann
    • , Ernst Rietschel
    • , Thomas Keil
    • , Sven Cichon
    • , Markus M. Nöthen
    • , Craig E. Pennell
    • , Peter D. Sly
    • , Carsten O. Schmidt
    • , Anja Matanovic
    • , Valentin Schneider
    • , Matthias Heinig
    • , Norbert Hübner
    • , Patrick G. Holt
    • , Susanne Lau
    • , Michael Kabesch
    • , Stefan Weidinger
    • , Hakon Hakonarson
    • , Manuel A. R. Ferreira
    • , Catherine Laprise
    • , Maxim B. Freidin
    • , Jon Genuneit
    • , Gerard H. Koppelman
    • , Erik Melén
    • , Marie- Hélène Dizier
    • , A John Henderson
    •  & Young Ae Lee
  • Article
    | Open Access

    Stiffness in the extracellular matrix is thought to contribute to pathological cutaneous fibrosis. Here, the authors identify the elastic fibre protein Fibulin-5 as a link and potential therapeutic target mediating the transition of cutaneous stiffening to fibrosis.

    • Manando Nakasaki
    • , Yongsung Hwang
    • , Yun Xie
    • , Sunny Kataria
    • , Rupali Gund
    • , Edries Y. Hajam
    • , Rekha Samuel
    • , Renu George
    • , Debashish Danda
    • , Paul M.J.
    • , Tomoyuki Nakamura
    • , Zhouxin Shen
    • , Steve Briggs
    • , Shyni Varghese
    •  & Colin Jamora
  • Article
    | Open Access

    To maintain viability, cells must be able to sense and respond to mechanical stimuli. Here, Qi et al. show that the STOML3 protein acts in mechanosensation by binding cholesterol and regulating membrane stiffness which can in turn regulate ion flux through mechanosensitive channels.

    • Yanmei Qi
    • , Laura Andolfi
    • , Flavia Frattini
    • , Florian Mayer
    • , Marco Lazzarino
    •  & Jing Hu
  • Article
    | Open Access

    The venom of the Chinese red-headed centipede causes excruciating pain. Here, Yanget al. identify a novel toxin protein from the centipede venom and find that it can activate the nociceptive TRPV1 ion channel by binding to the channel’s outer pore to potentiate the heat activation machinery.

    • Shilong Yang
    • , Fan Yang
    • , Ningning Wei
    • , Jing Hong
    • , Bowen Li
    • , Lei Luo
    • , Mingqiang Rong
    • , Vladimir Yarov-Yarovoy
    • , Jie Zheng
    • , KeWei Wang
    •  & Ren Lai
  • Article
    | Open Access

    Hyaluronan is a major component of the extracellular matrix, and is used to treat joint pain in osteoarthritis. In this study, Caires et al.show hyaluronan achieves its analgesic effects by targeting TRPV1 and stabilising the channel in its closed state.

    • Rebeca Caires
    • , Enoch Luis
    • , Francisco J. Taberner
    • , Gregorio Fernandez-Ballester
    • , Antonio Ferrer-Montiel
    • , Endre A. Balazs
    • , Ana Gomis
    • , Carlos Belmonte
    •  & Elvira de la Peña
  • Article |

    Sensory neurons that mediate histamine-independent itch express Mas-related G protein coupled receptors (Mrgprs). Here, Reddy et al.show that the cysteine protease cathepsin S cleaves and activates MrgpcrC11 without the generation of a tethered ligand, in contrast to other protease activated receptors.

    • Vemuri B. Reddy
    • , Shuohao Sun
    • , Ehsan Azimi
    • , Sarina B. Elmariah
    • , Xinzhong Dong
    •  & Ethan A. Lerner
  • Article |

    Aortic dissection and intramural haematoma are caused by separation of the aortic wall via an unknown mechanism. Here the authors show that the inflammatory cytokine, granulocyte macrophage colony-stimulating factor, is a central regulatory molecule causative of these conditions in mice and humans.

    • Bo-Kyung Son
    • , Daigo Sawaki
    • , Shota Tomida
    • , Daishi Fujita
    • , Kenichi Aizawa
    • , Hiroki Aoki
    • , Masahiro Akishita
    • , Ichiro Manabe
    • , Issei Komuro
    • , Scott L. Friedman
    • , Ryozo Nagai
    •  & Toru Suzuki
  • Article
    | Open Access

    Benzodiazepines (BDZs) target GABAA receptors to alleviate pain but these also cause side effects. Here the authors use mice in which only one GABAA receptor is BDZ-sensitive at a time to identify α2GABAAas the receptor that provides maximal analgesic activity but minimal side-effects in response to BDZs.

    • William T. Ralvenius
    • , Dietmar Benke
    • , Mario A. Acuña
    • , Uwe Rudolph
    •  & Hanns Ulrich Zeilhofer
  • Article |

    Sustained pressure on the skin reduces blood flow and causes wounds. Here the authors describe a flexible electronic ‘bandage’ that measures changes in tissue impedance spectra and detects early tissue damage in rats before it can be visualized, thus enabling possible prevention of pressure ulcers.

    • Sarah L. Swisher
    • , Monica C. Lin
    • , Amy Liao
    • , Elisabeth J. Leeflang
    • , Yasser Khan
    • , Felippe J. Pavinatto
    • , Kaylee Mann
    • , Agne Naujokas
    • , David Young
    • , Shuvo Roy
    • , Michael R. Harrison
    • , Ana Claudia Arias
    • , Vivek Subramanian
    •  & Michel M. Maharbiz
  • Article
    | Open Access

    Use of aromatase inhibitors for breast cancer therapy is associated with severe pain symptoms, the underlying mechanism of which is unknown. Here the authors show that in mice, TRPA1 is a major mediator of the proinflammatory and proalgesic actions of aromatase inhibitors.

    • Camilla Fusi
    • , Serena Materazzi
    • , Silvia Benemei
    • , Elisabetta Coppi
    • , Gabriela Trevisan
    • , Ilaria M. Marone
    • , Daiana Minocci
    • , Francesco De Logu
    • , Tiziano Tuccinardi
    • , Maria Rosaria Di Tommaso
    • , Tommaso Susini
    • , Gloriano Moneti
    • , Giuseppe Pieraccini
    • , Pierangelo Geppetti
    •  & Romina Nassini
  • Article |

    The upregulation of TRP ion channels is implicated in pain processing. In this study, the authors show that the zinc-finger protein ZBTB20 is responsible for TRP channel upregulation, and eliminating ZBTB20 from pain-sensing neurons in mouse models of pain results in the reduction of pain-like sensation.

    • An-Jing Ren
    • , Kai Wang
    • , Huan Zhang
    • , Anjun Liu
    • , Xianhua Ma
    • , Qing Liang
    • , Dongmei Cao
    • , John N. Wood
    • , David Z. He
    • , Yu-Qiang Ding
    • , Wen-Jun Yuan
    • , Zhifang Xie
    •  & Weiping J. Zhang
  • Article
    | Open Access

    TRPs are calcium-permeable channels involved in the sensing of damaging stimuli but the relationship between calcium influx and pain behaviour has been elusive. Here the authors find that the TRP channel OSM-9 functions as an ion channel in vivo in C. elegans, and establish residues that are critical for worm pain-like behaviour.

    • Amanda S. Lindy
    • , Puja K. Parekh
    • , Richard Zhu
    • , Patrick Kanju
    • , Sree V. Chintapalli
    • , Volodymyr Tsvilovskyy
    • , Randen L. Patterson
    • , Andriy Anishkin
    • , Damian B. van Rossum
    •  & Wolfgang B. Liedtke
  • Article |

    Unravelling the relationships between disease symptoms and underlying molecular origins is an important task in biomedical research. Here, Zhou et al.link diseases via their symptom overlap, and show that similar phenotypes are mirrored in networks that connect diseases with common genes or protein interactions.

    • XueZhong Zhou
    • , Jörg Menche
    • , Albert-László Barabási
    •  & Amitabh Sharma
  • Article |

    C-fibre polymodal nociceptors in primates have been classified into two groups based on their sensitivity to mechanical stimuli. Here, Wooten et al.describe how the differences in the response speed of the receptors to stimuli suggest that these should be considered as three separate groups.

    • Matthew Wooten
    • , Hao-Jui Weng
    • , Timothy V. Hartke
    • , Jasenka Borzan
    • , Amanda H. Klein
    • , Brian Turnquist
    • , Xinzhong Dong
    • , Richard A. Meyer
    •  & Matthias Ringkamp
  • Article
    | Open Access

    Genetically identical twins provide a valuable resource to identify epigenetic factors associated with complex traits. Here the authors adopt this approach and find that differential methylation of the pain gene TRPA1is associated with pain sensitivity in humans.

    • J.T. Bell
    • , A.K. Loomis
    • , L.M. Butcher
    • , F. Gao
    • , B. Zhang
    • , C.L. Hyde
    • , J. Sun
    • , H. Wu
    • , K. Ward
    • , J. Harris
    • , S. Scollen
    • , M.N. Davies
    • , L.C. Schalkwyk
    • , J. Mill
    • , Kourosh R. Ahmadi
    • , Chrysanthi Ainali
    • , Amy Barrett
    • , Veronique Bataille
    • , Jordana T. Bell
    • , Alfonso Buil
    • , Panos Deloukas
    • , Emmanoil T. Dermitzakis
    • , Antigone S. Dimas
    • , Richard Durbin
    • , Daniel Glass
    • , Elin Grundberg
    • , Neelam Hassanali
    • , Asa K. Hedman
    • , Catherine Ingle
    • , David Knowles
    • , Maria Krestyaninova
    • , Cecilia M. Lindgren
    • , Christopher E. Lowe
    • , Mark I. McCarthy
    • , Eshwar Meduri
    • , Paola di Meglio
    • , Josine L. Min
    • , Stephen B. Montgomery
    • , Frank O. Nestle
    • , Alexandra C. Nica
    • , James Nisbet
    • , Stephen O’Rahilly
    • , Leopold Parts
    • , Simon Potter
    • , Magdalena Sekowska
    • , So-Youn Shin
    • , Kerrin S. Small
    • , Nicole Soranzo
    • , Tim D. Spector
    • , Gabriela Surdulescu
    • , Mary E. Travers
    • , Loukia Tsaprouni
    • , Sophia Tsoka
    • , Alicja Wilk
    • , Tsun-Po Yang
    • , Krina T. Zondervan
    • , F.M.K. Williams
    • , N. Li
    • , P. Deloukas
    • , S. Beck
    • , S.B. McMahon
    • , J. Wang
    • , S.L. John
    •  & T.D. Spector
  • Article |

    Peptide drugs are attractive as therapeutics for gut-based applications, although they may be susceptible to reduction and degradation. Here, the authors develop seleno-oxytocin analogues, with enhanced stability at no cost to potency, and demonstrate their efficacy at colonic nociceptor inhibition in a mouse model.

    • Aline Dantas de Araujo
    • , Mehdi Mobli
    • , Joel Castro
    • , Andrea M. Harrington
    • , Irina Vetter
    • , Zoltan Dekan
    • , Markus Muttenthaler
    • , JingJing Wan
    • , Richard J. Lewis
    • , Glenn F. King
    • , Stuart M. Brierley
    •  & Paul F. Alewood