LOCUS COERULEUS-PAIN

ROLE OF LOCUS COERULEUS IN NEUROPATHIC PAIN

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 Obiettivo del progetto (Objective)

'The locus coeruleus, the main source of noradrenaline in the central nervous system, is a crucial step in both the descending and ascending pain modulatory systems which are compromised in neuropathic pain. Neuropathic pain is a chronic pathological condition arising from damage in the nervous system and that does not respond successfully to conventional analgesics. In fact, the first-line treatment approaches for neuropathic pain belong to drugs that modulate the activity of the locus coeruleus. In spite of this, LC role in neuropathic pain remains unknown. Locus coeruleus neuronal activity is modulated, among others, by G-protein-coupled receptors, α2-adrenoceptors presynaptically located. Indeed, the activation of these autoreceptors by noradrenaline circulating in the milieu active G protein-activated inwardly rectifying K channels (GIRK), hyperpolarizing the cell and inhibiting the release of the own neurotransmitter at LC level and projecting areas such as the spinal cord. This is a physiological feedback mechanism that control noradrenaline extracellular levels and consequently pain threshold. Thus, α2-adrenoceptors and GIRK channels seems to be a significant player in the locus coeruleus action potential frequency and therefore in the noradrenaline synaptic concentration. Thus, we suggest that they will play an essential role in ascending and descending pain transmission involved in neuropathic pain and that the knowledge of physiological processes responsible for their contribution to pain threshold will help to the design of a new line of anti-neuropathic drugs. We will tackle the project by implementing a broad range of techniques, from single-cell electrophysiology to whole-animal behavioural studies, and by correlating the results obtained by different techniques throughout the project.'

Introduzione (Teaser)

New evidence supports the use of anti-depressants to treat chronic pain. This comes as researchers uncover how the brain's stress circuitry changes in response to long-term pain.

Descrizione progetto (Article)

Pain is physically experienced in terms of its location, quality and intensity, as well as emotionally, in terms of how unpleasant if feels. Chronic pain can also lead to secondary emotions such as stress, which can develop into psychiatric disorders like depression and anxiety.

An area of the brain known as the nucleus locus coeruleus (LC) forms part of the central 'stress circuitry' involved in the development of these disorders. As part of the EU-funded 'Role of locus coeruleus in neuropathic pain' (LOCUS COERULEUS-PAIN) project, researchers examined the LC in relation to chronic pain.

They used an animal model (rats) to investigate symptoms seen in clinical settings in humans during chronic pain as a result of injury. These include experiencing pain in response to a stimulus that does not normally cause pain, and increased sensitivity to pain.

Researchers confirmed chronic pain leads to emotional disorders that outweigh the intrinsic suffering caused by a painful stimulation. The rats were unable to cope with stressful situations, which caused behaviours associated with depression and anxiety.

Upon examination of the LC, the project team noted alterations in the way some of its neurons function. Normally, the LC releases the stress hormone noradrenaline in response to pain. With chronic pain, this hormone is released constantly, causing a chemical imbalance that may cause mood disorders.

These findings offer biological evidence in support of the use of noradrenaline re-uptake inhibitors (anti-depressants) to treat chronic pain and its associated psychiatric disorders. They also provide insights into the underlying bases of these processes, which will help inform future research into the diagnosis and treatment of chronic pain.