The Pain Neuroplasticity and Modulation Laboratory

Pain perception is a dynamic process that can be influenced by the activity of endogenous pain modulation systems in the brain, brainstem and spinal cord before we perceive an unpleasant stimulus as ‘pain’.

The main focus of the Pain Neuroplasticity and Modulation Laboratory is to understand how pain perception is regulated by the central nervous system.  


We are particularly interested in exploring new ways to modulate the changes, or ‘neuroplasticity’, that occurs in the central nervous system during chronic pain. We are currently investigating innovative top-down pain relief strategies in human surrogate pain models in order to find new and more effective mechanism-driven therapies for chronic pain patients.

Modelling chronic pain mechanisms in healthy volunteers  

As the Pain Neuroplasticity and Modulation Laboratory Lead, Dr Sam Hughes uses different methods to induce temporary sensitisation in central pain pathways in healthy volunteers, including capsaicin cream and noxious electrocutaneous stimulation. These well-established human surrogate pain models are used to mimic key mechanisms of chronic pain, enabling us to gain the understanding required to advance effective therapies.

The goal of this research is to identify reliable quantitative sensory testing (QST) based approaches to measuring enhanced pain responses in unaffected skin areas, pain responses to normally non-painful stimuli, and endogenous pain modulation processes in healthy volunteers.

By gaining a better understanding of the mechanisms underpinning chronic pain, we are able to identify novel interventions that target altered pain processing in the central nervous system.

Using technology to harness endogenous pain relief

Sam also uses neuromodulation technologies, including virtual reality and non-invasive brain stimulation, alongside neurophysiological and psychophysical techniques to probe, measure and modulate endogenous pain relief in healthy volunteers during different pain states.

Sam was also recently awarded the Anthony Mellows Fellowship that provided the funding required to investigate the use of temporal interference (TI); a pioneering form of non-invasive deep brain stimulation, which he is currently exploring in human surrogate pain models using a combination of psychophysical and neuroimaging techniques. The aim is to better understand the influence of deeper brain regions, such as the anterior cingulate cortex, in endogenous pain control and to investigate whether this approach can be used to modulate pain neuroplasticity.

Exploring the link between sensory and affective components of chronic pain

Located in the Pain Neuroplasticity and Modulation group is the state-of-the-art laboratory for respiratory experimental designs (Lab R.E.D.). Anna Kharko has been heading the exciting line of research exploring the bidirectional relationship between pain perception and anxiety.  The lab uses the carbon dioxide (CO2) model, which involves the inhalation of a CO2 mixture, producing controlled respiratory and cardiovascular changes that mimic the effects of increased anxiety. Since April 2020, Lab R.E.D. has extended its research scope to anxiety related to the COVID-19 pandemic, running several projects investigating the effects on chronic pain.

Working with fellow researchers in the BRIC laboratories as well as with his collaborators at Imperial College London, Sam is also exploring the relationship between spinal nerve injury and clinical pain profiles in sciatica patients. Using diffusion tensor imaging (DTI) alongside clinical questionnaires and neurophysiological techniques, this research aims to understand the relationship between the underlying nerve damage and specific functional and symptom profiles.

Research expertise

Lab lead: Dr Sam Hughes, Lecturer in Human Neuroscience
Other research in this laboratory will be carried out by: Professor Stephen Hall, Dr Matt Roser, Professor Jonathan Marsden.

Key publications

Hughes SW, Hellyer PJ, Sharp DJ, Newbould RD, Patel MC & Strutton PH 2020 'Diffusion tensor imaging of lumbar spinal nerves reveals changes in microstructural integrity following decompression surgery associated with improvements in clinical symptoms: A case report' Magnetic Resonance Imaging 69, 65-70 , DOI

Hughes SW, Basra M, Chan C, Parr C, Wong F, Gomes S & Strutton PH 2020 'Capsaicin-Induced Changes in Electrical Pain Perception Threshold Can Be Used to Assess the Magnitude of Secondary Hyperalgesia in Humans' Pain Medicine , DOI

Hughes SW, Ward G & Strutton PH 2020 'Anodal transcranial direct current stimulation over the primary motor cortex attenuates capsaicin‐induced dynamic mechanical allodynia and mechanical pain sensitivity in humans' European Journal of Pain 24, (6) 1130-1137 , DOI

Hughes SW, Zhao H, Auvinet EJ & Strutton PH 2019 'Attenuation of capsaicin-induced ongoing pain and secondary hyperalgesia during exposure to an immersive virtual reality environment' PAIN Reports 4, (6) e790-e790 , DOI

Hughes SW, Hellyer PJ, Sharp DJ, Newbould RD, Patel MC & Strutton PH 2019 'Diffusion tensor imaging reveals changes in microstructural integrity along compressed nerve roots that correlate with chronic pain symptoms and motor deficiencies in elderly stenosis patients' NeuroImage: Clinical 23, 101880-101880 , DOI

Hughes S, Grimsey S & Strutton PH 2018 'Primary Motor Cortex Transcranial Direct Current Stimulation Modulates Temporal Summation of the Nociceptive Withdrawal Reflex in Healthy Subjects' Pain Medicine 20, (6) 1156-1165 , DOI

Hughes SW, Ali M, Sharma P, Insan N & Strutton PH 2018 'Frequency-dependent top-down modulation of temporal summation by anodal transcranial direct-current stimulation of the primary motor cortex in healthy adults' European Journal of Pain 22, (8) 1494-1501 , DOI

Hughes S, Hickey L, Donaldson LF, Lumb BM & Pickering AE 2015 'Intrathecal reboxetine suppresses evoked and ongoing neuropathic pain behaviours by restoring spinal noradrenergic inhibitory tone' PAIN 156, (2) 328-334 , DOI

Hughes SW, Hickey L, Hulse RP, Lumb BM & Pickering AE 2013 'Endogenous analgesic action of the pontospinal noradrenergic system spatially restricts and temporally delays the progression of neuropathic pain following tibial nerve injury' Pain 154, (9) 1680-1690 , DOI

Enhancing research through BRIC

The BRIC facility provides a collaborative and multidisciplinary research environment; with access to a range of psychophysical, neurophysiological, neuroimaging and non-invasive brain stimulation approaches, the Pain Neuroplasticity and Modulation Laboratory will investigate the sensitisation and modulation of central pain processing in both healthy volunteers and chronic pain patients.

The techniques used in the Pain Neuroplasticity and Modulation Laboratory include:

  • quantitative sensory testing
  • conditioned pain modulation
  • electrocutaneous stimulation
  • electromyography
  • human pain and anxiety models
  • temporal interference stimulation
  • transcranial direct current stimulation
  • virtual reality
  • functional MRI
  • diffusion tensor imaging.