Osteoarthritis: Interactions between endogenous brain opioids and the physiological and psychological responses to pain.

Lead Research Organisation: University of Manchester
Department Name: Medical and Human Sciences

Abstract

About 15% of the population have health problems due to arthritis and other associated conditions. The most common type of arthritis is osteoarthritis. The main reason why people with osteoarthritis go to see a doctor is pain. Pain is also the main reason why people with osteoarthritis lose their mobility. However the type of treatments available for people with osteoarthritis are very limited. Our research group has carried out studies that have shown that pain from osteoarthritis has an emotional effect on the brain that affects how pain is felt. This emotional effect could make a big difference to how patients respond to treatment or surgery. By reducing the effects of these emotions we could reduce how unpleasant the pain feels. This could also help to keep more people mobile. Our research aims to investigate how emotions such as anxiety and distress which affects how we feel pain, are altered by the natural painkillers made by the brain (opiates). We would like to approach people with osteoarthritis and ask them to take part in our study. Specifically, we would like to test a variety of people with different levels of anxiety and distress. We will make use of techniques that can produce images of the brain to measure the naturally occurring brain opiates, and how they affect how we expect (anticipate) and feel (give attention to) pain. These studies will help us explain how different people experience pain and why they respond differently to treatments. In the long term, they will also help us understand how the brains own painkillers work, and how we can improve on existing treatments for pain from osteoarthritis and also develop new therapies.

Technical Summary

Pain is the main cause of disability in patients with osteoarthritis (OA). However, there is a highly variable relationship between joint damage and the corresponding pain experience. We have established the brain structures that process pain in OA, and showed a greater response in areas concerned with affective processing such as the anterior cingulate cortex, prefrontal cortex, amygdala, hypothalamus and anterior insula.
These area are known to show changes in mu-opioid receptor availability in response to pain stimulation. We propose to study the effects of endogenous opioids (EO?s) in reducing pain processing within these brain areas. We will measure changes in opioid receptor binding in the brain to determine the brains production of EO?s in response to pain. We will assess: 1/ whether this is reduced in OA patients with psychological distress and 2/ if this correlates with altered ability to anticipate pain and switch attention away from the unpleasantness of pain. This will provide a step-change in our understanding of the physiology of pain perception in OA. It will facilitate more rational approaches to new therapies and existing treatments.
 
Title Improved metabolite analysis of C11 diprenorphine 
Description We have developed improved methods for separation and measurement of C11 diprenorphine metabolites. 
Type Of Material Technology assay or reagent 
Year Produced 2015 
Provided To Others? Yes  
Impact We have shared it with the Hammersmith PET group and are in the process of publishing it. This will make the method substantially more reliable. 
 
Title Radioactively labelled (carbon-11) diprenorphine 
Description Radiolabelled diprenorphine will be used as a radiotracer in our PET study. Displacement of diprenorphine from opioid receptors is a method of measuring the release of endogenous opioids, which compete with diprenorphine for binding to their receptors. 
Type Of Material Technology assay or reagent 
Year Produced 2009 
Provided To Others? Yes  
Impact This material will be used as part of a PhD degree by someone within the University of Manchester, but outside our research group. The material was also used as part of a research study conducted at the University of Bristol (Investigator: Hugh Sims-Williams). 
 
Description Development of enkephalinase inhibitors 
Organisation Debiopharm
Country Switzerland 
Sector Private 
PI Contribution Discussion of enkephalinase inhibitors designed for better brain penetration
Collaborator Contribution Advice and support moving forward towards phase 2 clinical trial in chronic pain
Impact None so far
Start Year 2009
 
Description Development of enkephalinase inhibitors 
Organisation Pharmaleads
Country France 
Sector Private 
PI Contribution Discussion of enkephalinase inhibitors designed for better brain penetration
Collaborator Contribution Advice and support moving forward towards phase 2 clinical trial in chronic pain
Impact None so far
Start Year 2009
 
Description Press release 2015 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact People can raise pain threshold by altering brain chemistry, arthritis patients study shows - http://www.manchester.ac.uk/discover/news/people-can-raise-pain-threshold-by-altering-brain-chemistry-arthritis-patients-study-shows/
Year(s) Of Engagement Activity 2015
URL http://www.manchester.ac.uk/discover/news/people-can-raise-pain-threshold-by-altering-brain-chemistr...
 
Description Press release 2015 - Mail Online 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Scientists discover how to 'turn off' pain: Threshold can be raised by altering chemistry in the brain

Read more: http://www.dailymail.co.uk/health/article-3286646/Scientists-discover-turn-pain-Threshold-raised-altering-chemistry-brain.html
Year(s) Of Engagement Activity 2015
URL http://www.dailymail.co.uk/health/article-3286646/Scientists-discover-turn-pain-Threshold-raised-alt...
 
Description Radio Interview - BBC World service 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact The first chemical proof of our brain adapting to chronic pain
Year(s) Of Engagement Activity 2015
URL http://www.bbc.co.uk/programmes/p035smn7
 
Description press release 2015 - Times of India 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Pain threshold rises with altered brain chemistry
Year(s) Of Engagement Activity 2015
URL http://timesofindia.indiatimes.com/home/science/Pain-threshold-rises-with-altered-brain-chemistry/ar...