Around 3% of adults in the UK today take opioids for non-cancer-related chronic pain. One of the unwanted side effects of opiates is sleep disturbance, and this is thought to be an important risk factor in opioid-related deaths. Sleep disturbance is also associated with increased sensitivity to pain. But can opioids make pain worse by disturbing sleep?
Bristol researchers are investigating the brain processes underlying opioid therapy and sleep disturbance in chronic pain patients, to help identify patients at risk of opioid-related side effects and guide safe prescription of these drugs in treating pain.
Many of the brain areas known to control breathing and pain are rich in opioid receptors. This makes it difficult to disentangle the effects of opioid medication on breathing and pain, both of which may affect the quality of sleep experienced by patients.
Dr Jonathan Brooks at the School of Experimental Psychology, with colleagues Dr Claire Durant, Ms Lee Harrison and Dr Sue Wilson, set out to measure sleep patterns in patients with chronic low back pain to see whether opioid-related sleep disturbance influenced the amount of pain reported. Funding for an initial feasibility study was provided by the Elizabeth Blackwell Catalyst Fund, which supports novel interdisciplinary research.
Dr Brooks and his team worked with a multidisciplinary group of clinicians at North Bristol NHS Trust (Dr Cathy Stannard, Dr Johanna Herrod, Dr Kyle Heron) and University Hospitals Bristol NHS Foundation Trust (Dr Tony Pickering, Dr Charlotte Steeds). The work also involved a collaboration with Dr Kyle Pattinson at Oxford University, who was doing complementary research in this area.
Together they recruited and screened 48 patients, of whom 15 were judged eligible for the study, with 13 patients completing it in full. The research included monitoring patients’ electrical brain activity and breathing during sleep, either at the Clinical Research and Imaging Centre (http://www.cricbristol.ac.uk) or at home. In particular, researchers wanted to see whether patients on high doses of opioid medicines had worse sleep than those with similar levels of pain who were not using opioids.
The morning after sleep monitoring, researchers tested patients’ ability to detect normally painful stimuli, such as painful heat or sharp needles applied to the skin, adapting an established protocol from the German Research Network on Neuropathic Pain. The aim was to determine whether the quality of patients’ sleep affected their ability to detect and suppress pain, and whether opioids could actually make patients’ pain worse by disturbing their sleep.
The team also used magnetic resonance imaging (MRI) to scan the brains of two patients to see whether the parts of the brain that normally help control pain are affected by poor sleep.
The study resulted in an agreed method (protocol) for recruiting and monitoring sleep and pain in patients with chronic back pain on different doses of opioids. This included the option of sleep monitoring in hospital for two nights (polysomnography), or two weeks of monitoring at home using a wrist-worn device (actigraphy), with patients keeping a sleep and pain diary. Researchers also established a way to test pain levels that is well tolerated by patients, and use of a new MRI technique with shorter scan times that is more easily borne by people with back pain.
Dr Brooks has since presented an outline of the study to the British Neuroscience Association, and Dr Durant has raised awareness among Bristol physiotherapists and occupational therapists through talks and collaborations. The initial results of the study were presented at the 16th World Congress on Pain in Yokohama, Japan.
As part of an ongoing collaboration with Dr Pattinson at Oxford University, the team is also preparing a joint paper on the effects of opioids on sleep behaviour and pain sensitivity which pools their research data, along with a grant application for a multi-centre trial on pain modulation and sleep monitoring. Further collaborations are also planned in the area of pain and breathing, as well as a potential new line of research on how converting patients from high opioid doses to methadone affects sleep patterns.