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Interactions between melatonin and endogenous opioid peptide release


Project Description

Overview:

Control of pain remains a challenge for medicine. Melatonin, known for its role in circadian regulation, also has antioxidant and anti-inflammatory actions and has been suggested to have analgesic effects in a range of pain syndromes. We have shown that melatonin treatment reduced pain behaviour in a rat model of neuropathic pain. The neuro-immune axis contributes to the endogenous control of pain. M2 macrophages have an important role in resolution of inflammation and contribute to endogenous analgesia via release of endogenous opioids. Both opioid peptide and endogenous melatonin release from macrophages is elicited by inflammatory mediators and β adrenergic activation. There is some evidence that exogenous melatonin augments endorphin release from pituitary cells, but the effects in macrophages are not known.

It is not clear whether endorphin-melatonin interactions in the brain are different to that in inflammatory immune cells, but it is known that inflammatory stimuli of pineal cells down-regulates endogenous melatonin whereas the same stimuli up-regulate it in macrophages, thought to be due to the expression patterns of the different NFκB dimers. The student will study both pituitary cells and macrophages to represent the neuro-immune axis. The precise interaction between opioid peptides and melatonin is unclear- however melatonin may augment endorphin release e.g. from macrophages, as a potential mechanism for the effects of exogenous melatonin on pain at sites of inflammation.

The aim of this studentship is to investigate the interactions between endogenous melatonin and opioid peptide release in macrophages and pituitary cells in response to a variety of mediators, and the effects of exogenous melatonin receptor agonists on opioid peptides and vice versa. The mechanisms driving these processes will be investigated.

The student will also be able to use samples from a trial of melatonin in patients with chronic pain to enable the endogenous opioid peptide profile to be determined in patients receiving melatonin treatment (full trial details are available at http://www.isrctn.com/ISRCTN12861060 )

The results will identify the extent of co-regulation of endogenous opioid peptides/melatonin and will involve cell culture, RT-PCR, western blotting, enzyme immunoassay and working with human samples.

Further more detailed project information is available by emailing


APPLICATION PROCEDURE:
Formal applications can be completed online: https://www.abdn.ac.uk/pgap/login.php. You should apply for Degree of Doctor of Philosophy in Medical Sciences, to ensure that your application is passed to the correct person for processing.

Funding Notes

This project is funded by the British Journal of Anaesthesia and the Royal College of Anaesthetists. The duration of the degree programme is 3 years (36 months) and full funding is available to UK/EU applicants only (tuition fees at EU/UK rate and MRC stipend rates with consumable costs).

Candidates should have (or expect to achieve) a minimum of a 2.1 Honours degree in a relevant subject. Applicants with a minimum of a 2.2 Honours degree may be considered provided they have a Merit/Commendation/Distinction at Masters level.


References

Available by emailing [email protected]

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