Time plays a key role in our perception of pain and administering pain relief and medication for chronic pain-related depression may be more effective at certain times of day, UCL and University of Toronto researchers say.
In an article published in Science, the researchers commented on two new, separate studies by two different teams of Chinese researchers published in the same journal, one into acute pain and one into chronic pain.
Pain is both an unpleasant sensory and emotional experience in response to actual or perceived injury. Sights and sounds are processed through specific regions of the brain (known as the visual and auditory cortices) but there is no corresponding pain cortex.
It is also well known that if pain becomes chronic - that is, it lasts for more than three months - then side effects can include disability and emotional dysregulation, of which depression, anxiety and sleep disorders are the most common.
However, the mechanism by which chronic pain translates into these debilitating conditions has, until now, been poorly understood.
In their article , Associate Professor Simon Beggs (UCL Great Ormond Street Institute of Child Health) and the University of Toronto’s Department of Physiology Senior Scientist Paul Frankland, were asked to compare the two studies by the Chinese researchers.
In the first paper, From chronic pain to depression: Neurogenesis-driven microglial remodeling in the hippocampal dentate gyrus , a team led by Ming Ding from China’s Fudan University revealed how chronic pain leads to a re-wiring of the brain’s neural circuitry: depression in this context is not a secondary emotional response, but a physiological change to the brain.
Experimenting on mice and also by looking at thousands of images of the human brain stored in the UK Biobank database, they noticed that the hippocampus - the part of the brain that regulates emotion - initially expands in response to pain in a positive way but then, as the pain persists, shrinks thereby reducing an individual’s ability to regulate their emotions.
In their article, Beggs and Frankland say this is the first time researchers have clearly identified this mechanism and that Ding et al’s findings help explain why around 85% of people with chronic pain also experience depression and why certain antidepressants can be effective for managing both mood and pain.
In a second paper, on acute pain, called Hypothalamic clock governs circadian pain , a team led by Hong-Rui Wei from Hefei’s University of Science and Technology of China wanted to explore why pain sometimes feels stronger in the morning or evening, even when an individual’s injury remained the same.
Studying mice with nerve injuries which made them feel long lasting pain, Wei and his team checked how sensitive the mice were to gentle touches or heat at different times of day.
They found that in the daytime (their rest cycle) the mice felt pain much more strongly and at night (their waking/active cycle) the same level of pain felt much weaker.
They then looked at a specific region of the mice’s brains called the suprachiasmatic nucleus (SCN) within the hypothalamus.
This small cluster of roughly 20,000 neurons acts as the main pacemaker for the body’s 24-hour cycle - also known as its circadian clock - and uses light cues from the eyes to synchronize biological processes like sleep, temperature and hormone release.
What Wei and his team found was that the SCN also controls pain sensitivity, the mice’s body clocks turning the pain "signal" up during the day and down at night.
In their paper, Wei and his team say their discovery offers a "mechanistic framework for chronotherapeutic strategies in pain management" - if pain has a daily rhythm, then medicines might work better if given at certain times rather than others, a medical technique known as chronotherapy, they say. In the UK alone, there are millions of people living with long-lasting pain.
Associate Professor Beggs said: "Recognising that the level of pain an individual feels changes over time has important implications.
"It highlights pain as a critical variable in pain measurement and treatment. Chronotherapeutic approaches that optimise the timing of pain relief or antidepressant medication may improve how effective those treatments are."
Study limitations
Both studies only used male mice despite the overwhelming evidence that chronic pain, depression, circadian regulation and neuroimmune mechanisms differ substantially between the sexes.
Chronic pain can lead to depression.
Nick Hodgson
(0)7769 240209
Email: nick.hodgson [at] ucl.ac.uk
University College London, Gower Street, London, WC1E 6BT (0) 20 7679 2000
