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Molecular Nociception

The Molecular Nociception Group focuses on genetic approaches to understanding the biology of nociceptors (damage-sensing neurons), somatosensation, pain and touch.

Our research

The twenty-first century has seen a revolution in our understanding of the receptor systems and regulatory pathways that underlie the responses of nociceptors to the occurrence of tissue damage. This has important implications for human health and disease.

We collaborate with research groups in Europe, the United States, Korea, Japan, and Australia, using transgenic mouse models, natural products, and cloned genes to explore the physiology of pain perception. The systems we study have a broad relevance to understanding how the nervous system works in terms of synaptic plasticity, responses to environmental stimuli, sensation, and behaviour.

Sensory Neurobiology

Lead: Prof. John Wood

Our research team focuses on genetic approaches to understanding the biology of damage-sensing neurons (nociceptors), somatosensation, pain and touch. Pain is still an enormous clinical problem, and new drugs are urgently required for a range of chronic pain syndromes.

Our group combines recombinant DNA technology, electrophysiology, gene targeting and behavioural approaches to explore the channels, receptors, transcription factors and regulatory pathways that control nociceptor excitability. 

We collaborate closely with human geneticists and clinicians, using mouse models to unravel molecular mechanisms that underlie pain disorders. We also take part in early-stage drug discovery programmes based on targets we identify in the lab.

As well as providing information about pain pathways, the systems we study have a broad relevance to understanding how the nervous system works, in terms of synaptic plasticity, responses to environmental stimuli, sensation and behaviour.

Light touch (red) and damage-sensing (green and blue) neuron cell bodies from spinal ganglia

Touch sensing neurons (green) are associated with Merkel cells (red)

In the absence of a PDZ protein, light touch can no longer be detected

Resources

Mechanistic Studies of Somatosensory Pathways

Lead: Dr Jing Zhao

Our studies are focused on sensory transduction and transmission in the peripheral nervous system, especially in pain signalling. We use gene targeting in and transgenic mice as a model, combining molecular biochemistry, electrophysiology, and behavioural approaches to identify the genes or molecules involved and to understand the molecular, cellular, physiological and pathological mechanisms involved.

We have three main areas of research:

  • trafficking of sodium channel Nav1.7
  • BDNF in pain signalling, 
  • microRNAs in pain signalling.

Group members

  • Ayako Matsuyama (PhD student)
  • Kieran Miller (Year 3 student, Intercalated BSc)

Neural marker expression in dorsal root ganglion

c-Fos staining in spinal cord

Mammalian Sensory Genetics

Lead: Prof. James Cox

Prof. Cox investigates the genetic basis of rare human pain disorders, such as:

  • Channelopathy-associated Insensitivity to Pain (SCN9A/NaV1.7)
  • Familial Episodic Pain Syndrome (TRPA1)
  • Marsili Syndrome (ZFHX2)
  • FAAH-OUT-associated Human Pain Insensitivity.

His team is particularly interested in how long non-coding RNAs regulate key pain genes and the endocannabinoid system. A major goal is to translate genetic findings into new analgesic gene therapies.

Group members

  • Dr Abdella Habib | Research Associate
  • Ayako Matsuyama | Research Technician and PhD student
  • Shengnan Li | PhD Student

Inheritance of primary erythromelalgia

A family pedigree of pain insensitivity

Transcriptional and Post-Transcriptional Control of Pain

Lead: Dr Andrei Okorokov

Pain is a major clinical problem and affects more people than diabetes, heart disease and cancer combined. Pain is a co-factor in many medical conditions, yet pain medicines are often only partially effective, and the problem is increasing with an aging population. By understanding the cellular and molecular processes that lead to the sensation of pain, more effective targeted therapies can be developed to alleviate suffering.

One way of doing so is analysing genetic conditions in which patients have altered levels of pain sensitivity, in particular the cases where pain sensitivity and perception are diminished. Identifying human genes, which are responsible for such a phenotype and their functional products, allows us to pinpoint the key players in the chain of molecular events providing for pain sensation.

After two decades of work in transcriptional and post-transcriptional regulation of tumour suppression (p53 field), I am now establishing a new research direction into the transcriptional and post-transcriptional regulation of pain pathways.

Neural Circuits for Pain

Lead: Dr Liam Browne

The goal of the Browne Lab is to understand how the brain processes pain. Pain is a protective system that alerts us to potential damage. When this alarm system goes wrong, pain can become highly debilitating and a disease in itself. Chronic pain is a global health issue affecting 1 in 5 people and treatments are inadequate, representing a huge unmet clinical need. We aim to provide a mechanistic understanding of the neural circuit computations that contribute to pain, and how they are altered in disease. This can inform targets for treatments for pain and provide core insights into the operation of the nervous system more broadly. 

We take a multidisciplinary approach at the interface between neuroscience, physiology, and engineering, using custom behavioural approaches, in vivo 2P microscopy, optogenetics, electrophysiology, and machine vision and machine learning. We have two areas of focus:

  • Probing how pain is encoded and expressed by the cerebral cortex
  • Developing advanced tools for studying behaviour, from reflexes to learning.

These areas overlap, allowing us to map the relationship between pain, emotion, motivation, learning and decision-making in health and disease.

A brain lit in one area

Brain waves on a reader

Laser omitting blue light

Our experts

Prof John Wood portrait

Prof. John Wood (Head)

James Cox profile

Prof. James Cox

Dr Jing Zhao

Dr Jing Zhao

Dr Andrei Okorokov

Dr Andrei Okorokov

Basic silhouette in a circle, in light grey

Dr Ana-Paula Luiz

Basic silhouette in a circle, in light grey

Dr Manuel Arcangeletti

Basic silhouette in a circle, in light grey

Dr Federico Iseppon

Dr Naxi (Arki) Tian

Dr Naxi (Arki) Tian

Technical Support

  • Sam Gossage
  • Sonia Santana-Varela
  • Queensta Millet

Students

  • Rayan Abdalla
  • Clarissa Butti
  • Janvi Patel
  • Sana Zuberi
  • Swee Leng Lee

Molecular nociception group picture

Selected publications

  1. Mikaeili H, Habib AM, Yeung CW-L … Wood JN, Okorokov AL, Cox JJ (2023). Molecular basis of FAAH-OUT-associated human pain insensitivity.
  2. Wood, JN (2022). Pain, purines and Geoff. Autonomic Neuroscience, Basic & Clinical, 237, ARTN 102902.
  3. Iseppon F, Linley JE, & Wood, JN. (2022). Calcium imaging for analgesic drug discovery. Neurobiology of Pain, Volume 11, January–July 2022, 100083.
  4. MacDonald DI, Luiz AP, Millet Q, Wood JN, et al. (2021). A central mechanism of analgesia in mice and humans lacking the sodium channel Naᵥ1.7. Neuron.
  5. Raoof R, Gil CM, Lafeber FPJG, ... Wood JN, Mastbergen SC, Eijkelkamp, N. (2021). Dorsal Root Ganglia Macrophages Maintain Osteoarthritis Pain. Journal of Neuroscience, 41 (39), 8249-8261.
  6. Cibert-Goton V, Lam C, Lingaya M, Falcone Y, Wood JN, Bulmer DC & Spiller, R. (2021). Pain Severity Correlates With Biopsy-Mediated Colonic Afferent Activation But Not Psychological Scores in Patients With IBS-D. Clinical and Translational Gastroenterology, 12 (2), ARTN e00313.
  7. MacDonald DI, Luiz AP, Iseppon F, Millet Q, Wood JN, et al. (2021). Silent cold-sensing neurons contribute to cold allodynia in neuropathic pain. Brain. 2021 Jul 28;144(6):1711-1726.
  8. Theofanous SA, Florens MV, Appeltans I, Denadai Souza A, Wood JN, Wouters MM & Boeckxstaens GE (2020). Ephrin-B2 signaling in the spinal cord as a player in post-inflammatory and stress-induced visceral hypersensitivity. Neurogastroenterol Motil. 2020 Apr;32(4):e13782.
  9. MacDonald DI, Wood JN, & Emery EC. (2020). Molecular mechanisms of cold pain. Neurobiology of Pain, 7, 100044.
  1. Ter Heegde F, Luiz AP, Santana-Varela S ... Wood JN, Chenu C. (2020). Osteoarthritis-related nociceptive behaviour following mechanical joint loading correlates with cartilage damage. Osteoarthritis Cartilage. 2020 Mar;28(3):383-395.
  2. de Clauser L, Santana-Varela S, Wood JN, & Sikandar S. (2020). Physiologic osteoclasts are not sufficient to induce skeletal pain in mice. Eur J Pain. 2021 Jan;25(1):199-212. 
  3. de Clauser L, Luiz AP, Santana-Varela S, Wood JN, et al. (2020). Sensitization of Cutaneous Primary Afferents in Bone Cancer Revealed by In Vivo Calcium Imaging. Cancers, 12 (12), 1-19.
  4. Alles SRA, Nascimento F, Luján R, Luiz AP, Millet Q, Bangash MA ... Wood JN. (2020). Sensory neuron–derived Naᵥ1.7 contributes to dorsal horn neuron excitability. Science Advances, 6 (8).
  5. Luiz AP, MacDonald DI, Santana-Varela S, Millet Q, Sikandar S, Wood JN, Emery EC. Cold sensing by NaV1.8-positive and NaV1.8-negative sensory neurons. Proc Natl Acad Sci U S A. 2019 Feb 26;116(9):3811-3816.
  6. Wood, John N. (ed.), The Oxford Handbook of the Neurobiology of Pain (2020; online edn, Oxford Academic, 10 July 2018).
  7. Ter Heegde F, Luiz AP, Santana-Varela S, Wood JN, et al. (2019). Non-invasive mechanical joint loading as an alternative model for osteoarthritic pain. Arthritis Rheumatol 2019 Jul;71(7):1078-1088.
  8. Habib, AM, Matsuyama A, Okorokov, AL, Santana S, ... Wood JNCox JJ. (2018). A novel human pain insensitivity disorder caused by a point mutation in ZFHX2. Brain. 2018 Feb 1;141(2):365-376.
  9. Sikandar S, Minett MS, Millet Q, Santana-Varela S, Lau J, Wood JN, Zhao J, et al. (2018) Brain-derived neurotrophic factor derived from sensory neurons plays a critical role in chronic pain. Brain. 2018 Apr 1;141(4):1028-1039.

Facilities

Molecular nociception group picture

Related programmes

Researchers within the Wolfson Institute for Biomedical Research contribute to several distinguished taught courses at UCL.

 Group activities

Members of the Molecular Nociception Group at a restaurant

Molecular nociception visit group picture

Molecular nociception brazilian pharcologists group picture

The Molecular Nociception Group at a restaurant table