Research

Pain is a conscious experience, an interpretation of the nociceptive input influenced by memories, emotional, pathological and cognitive factors. The behavioural response by a subject to a painful event is modified according to what is appropriate or possible in any particular situation. Pain is, therefore, a subjective experience as illustrated by the definition given by The International Association for the Study of Pain (IASP): ‘‘An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.’’

Chronic pain (pain that persists or recurs for more than 3 months) is one of the largest medical health problems in the developed world, affecting about 20% of the adult population, particularly women and the elderly. The predictions are that similar statistics or perhaps worse exist for the undeveloped world, however, this data is currently unavailable. Management and treatment of chronic pain is unmet, therefore chronic pain is a global problem creating an enormous emotional and financial burden to sufferers, carers and society in general.  Innovative methods are needed if we are to combat this massive and growing problem.  

Until recently it has been difficult to obtain reliable objective information from healthy volunteers and patients regarding their subjective experience of pain. Since the introduction of functional neuroimaging methods, such as functional magnetic resonance imaging (FMRI), positron emission tomography (PET) and electroencephalography (EEG), we have been able to show robust and reproducible activation in response to nociceptive (i.e. painful) stimuli within the human brain and spinal cord.  This activation can be related to what the subject describes and issues such as how anxiety, attention, distraction and anticipation alter pain perception better understood. In short, we can unravel the workings of pain perception at a neuronal level.

Functional magnetic resonance imaging in particular is ideal for such investigations in humans, as its temporal and spatial resolution enable sophisticated experimental designs to be developed that can determine the neuroanatomical substrate for these processes. Several of our previous experiments have specifically isolated areas of the cerebral cortex that are central to the processes involved in expecting pain, being anxious about pain and altering your attention to pain and where relevant these aspects of the pain experience have been related to clinical pain syndromes.

Correlating specific neurophysiological markers to the perceptual changes induced by pharmacological agents and identifying their site of action within the human nervous system has also been a major goal for drug discovery. Recently, pharmacological functional magnetic resonance imaging (phMRI) methods have been developed and applied to the field of pain research. phMRI is a method that combines FMRI with drug delivery to determine the site of drug action or the modulation by the drug on brain regions activated in response to either a sensory, motor or cognitive input. The completely non-invasive nature of FMRI enables longitudinal studies on healthy subjects and patients making it ideal for use in combination with pharmacological agents that might require multiple dosing across many imaging sessions or a serial collection of imaging data across time due to the pharmacokinetics of the drug.

Many advances in the field of phMRI have been made in studies by our laboratory. Novel pharmacodynamic information has been determined spatially across the human brain using remifentanil (short acting opoid analegesic drug) in combination with a painful stimulus. FMRI has also been used in combination with 'gold-standard' drugs that are currently used in the treatment of chronic pain. We have applied phMRI to gain a better understanding of action of these compounds in both human models of clinical pain as well as neuropathic and inflammatory pain patients. More recently, the ability to simultaneously record EEG and FMRI signals has been developed by our laboratory. This enables data with high spatial and temporal resolution to be obtained and this new technological development, along with developments in spinal cord functional imaging, will be applied to healthy subjects, patients as well as studies investigating drug effects targeted for pain alleviation.