Rationale and aim
Peripheral nerves respond to changes at the surface or inside our body, the brain then interprets these responses in terms of tactile or visceral sensations, such as heat, touch, or pain. Until now, accepted scientific theory has held that only the central nervous system could interpret and analyse such sensations. The peripheral nerves were seen mainly as wires relaying information to the brain. Our recent findings challenge this view and suggest that the peripheral nervous system could be capable of interpreting its environment and modulating pain independently of the central nervous system. The overarching goal of this programme is to develop a comprehensive understanding of how peripheral nerves can regulate and control pain.
Value for society
These studies will change current understanding of somatosensory processing and will provide new ideas for pain treatment. The additional value is in the identification of peripheral nervous system as a robust target for pain control. Most current pain treatments target the brain (eg most clinically used analgesics, including the opioids). Centrally acting analgesics are notorious for their bad side-effects, including tolerance and addiction, which fuel world-wide pandemics of opioid drug abuse. We hope that our hypothesis will enable development of peripherally-acting therapies that are devoid of side effects of narcotic analgesics.
Plan of work
We have discovered that each peripheral nerve in mammals has its own ‘mini-brain’ – an organ capable of modulating signals conducted by the nerve. Cutting edge methods of molecular, cellular and behavioural neuroscience will be used to answer how these mini brains operate and how can we use them to control pain.
The number of animal experiments will be reduced whenever possible. Alternative approaches, such as mathematical modelling, will also be extensively used. A large share of our experiments will be done with cultured neurons. In the in vivo experiments we will keep the group size to a minimum sufficient to detect significant changes between the groups.
We will only use pain models that are well established in the field. In most cases in these models animals only experience relatively mild distress, close to the threshold of feeling discomfort. Some of the experiments will be of moderate severity. Lesions to peripheral nerves or peripheral inflammation may result in moderate hyperalgesia and in some distress associated with it. As animals are checked daily, signs of significant discomfort will result in immediate sacrifice of the animal with humane schedule 1 procedure.
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