RESEARCH INTERESTS
Our research has been based on understanding the transmission and control of pain related to improving its treatment, either through better knowledge of mechanisms or characterization of novel targets. The approach has been to understand how pain changes the nervous system.The groupI have studied how neuronal systems alter in patho-physiological states and how novel and licensed drugs produce their effects on pain processes. We have made many major advances in this area and the aim has been to translate the basic research into clinical applications.

Early on we described Diffuse Noxious Inhibitory controls (DNIC) and subsequently provided a detailed description of their neural basis. DNIC are used as a possible diagnostic in chronic pain patients. At UCL, our original pioneering work on the neuronal actions of opioid receptors lead to major advances in opioid function, the idea of pre-emptive analgesia and other important clinical translations. We were the first group to show the NMDA receptor mediation of wind-up, then its role in persistent pain. This and our continuing work on central hyperexcitability has been seminal in understanding of pain in animals and humans.
We further initiated some of the very first studies on the pharmacology of the developing spinal cord related to paediatric pain control. We have studied a number of novel mediators ranging from nitric oxide, adenosine, nicotinic ligands and newer opioids. Assessment of drug combinations has also guided clinical practice.

More recently, we have taken our work on the plasticity of spinal signalling after inflammation to other pain states to examine changes after nerve injury and adapted and further developed a rodent model of bone cancer, all of which have informed clinical practice. At the same time we have some very fruitful collaborations with molecular groups. We have provided evidence for roles of targets that include sodium channels found in peripheral neurons and central G-protein linked receptors within integrated systems using levels and ranges of stimuli that cannot be assessed by behavioural approaches. Further advances using pharmacological tools are exemplified by functional identification of roles for Kv7/M and other potassium channels that could be novel pain targets. Ongoing active studies include assessing tissue specific knock-outs with Prof J Wood, and our original extensive work on calcium channel function in pain has lead to international collaborations on the roles of splice variants and over-expressing of calcium channel subunits. Finally, in the last 2 years, our original studies with novel techniques on spinal neurones that project to the brain and engage descending brainstem serotonergic influences to the cord to enhance spinal excitability have had major implications for the understanding how pain shapes emotional changes. We have shown the integrity of this pathway is a crucial determinant of both the abnormal neuronal and behavioural manifestation of nerve injury. This pathway also has a major bearing on efficacy of drugs used in neuropathic pain and has been verified in humans through imaging and clinical trials of novel analgesics.