Past, Present, Pain

Could pain we experience early in life increase our sensitivity to pain in later years?

Written by: Fatema Zavery & Jason Arunn Murugesu

Art by: EJ Oakley and Winnie Lei


‘People are very judgemental about pain’ notes Professor Maria Fitzgerald, a Principle Investigator of UCL’s Paediatric Pain Research Group. She suggests that this is because we all judge each other on some concept of a  ‘norm’. However, Fitzgerald  argues  that no such norm actually exists; this view is outdated and does more harm than good.  

The Paediatric Pain Research Group in UCL, or PPNG for short, have two primary aims: to expand our knowledge on neurobiological pain pathways and to improve the clinical treatment of children in pain.

Hubel and Wiesel’s infamous experiments in the late sixties demonstrated that early life was key to the development of the senses. One experiment involved two cats of differing ages: a newborn kitten and an adult. In both cats, one eye was shuttered and reopened six months later. The reopened eye of the adult cat was unaffected, whereas in the newborn kitten, fewer neurons in the eye were activated in response to light. Hubel and Wiesel’s research centered on the ocular dominance columns in the eyes and concluded that the development of these columns could only be affected at a very young age. They called this period the ‘critical window’.

The ‘critical window’ is the focus of the research conducted by PPNG. Does the pain we feel in the ‘critical window’ affect the pain we feel later in life?

In 2012, PPNG, alongside other researchers, presented a study centered around this debate. Like Hubel and Wiesel, adults were compared to newborns. In this case, however, rats were used – times have changed. The newborns were cut on their hindpaw and allowed to grow into adults.

The adult rats who had been injured as newborns were said to be ‘primed’. The concept of priming can be likened to a long-held grudge that never goes away; whilst it may not affect your daily life, it rears its ugly head when provoked. The researchers carried out such a provocation  when they cut the ‘primed’ rats on their hindpaws once more as adults. As a control, they also cut the hindpaws of a set of adult rats who had not been injured as newborns.

The two groups of rats were observed for four weeks and tested for hyperalgesia, or increased sensitivity to pain.  The primed rats presented significantly higher levels of hyperalgesia.

rat.jpg

The study also attempted to highlight the mechanism for priming. Who or what actually holds the grudge? It is generally believed that priming involves neuroimmune interactions, in particular the microglial cells. Microglial cells are only found in the central nervous system and can be considered the caretakers of the brain. They generally maintain its health and wellbeing. However sometimes they do more harm than good, especially in a developing brain – like an overbearing mother.

The experiment was straightforward: what happens if you stop these caretakers from doing their jobs? An inhibitor of microglia was administered to both sets of rats, those that were primed and those that were not. Unlike in the previous experiment, the primed rats experienced no increased sensitivity to pain when cut on the hindpaw.

In addition to several mice and rat models on priming, experiments have also been conducted on humans; we need to know how cutting the hindpaws of rats affects our interpretation of pain! As such, using the basis of priming, EPICure studies were carried out.

EPICure is a series of studies conducted on the long term health of children that were born preterm. Dr Suellen Walker, a Principal Investigator of PPNG, compared 43 of these children to age matched children that were not born preterm. The advantage of working with children was that they were able to ask the subjects questions. The disadvantages were that they could not test using noxious stimuli or pain thresholds. Intriguingly the study found that whilst the mechanical responses were the same for the two sets, the EPICure children were less thermally sensitive. Walker suggests this may be due to the modulation of C-fibre pathways. These fibres play a significant role in pain perception.

Walker is a medical doctor by trade and works as a Consultant in Paediatric Anaesthesia and Pain Medicine at Great Ormond Street Hospital. PPNG’s findings are therefore not confined to the lab, but affect the day-to-day practice of pain management for children.

Considering pain management for the wider population, however, Walker argues that historical methods that merely divide the origin of pain into physical or psychological have proven to be fatal oversimplifications. As such, PPNG is calling for improved identification, diagnosis, and treatment for the management of pain, particularly chronic pain. In a recent study, this condition was found to affect between one third to half of all adults in the UK.

Fitzgerald mused on the damning effects to our lives that are unique to pain. When we are in pain, she says it is our ‘most dominant thought’, it ‘modifies our behaviour’ and ‘modifies our emotion’- and yet it is so difficult to describe our pain to others. This fundamental nature of pain is what makes it so difficult to understand. We have only scratched the surface, and UCL’s Pain Paediatric Research Group are at the forefront of our future insight.

 

 

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