A peek into the world of pain
Understanding pain has been one of human beings' oldest quests. Pain has been condemned as worse than death and celebrated as a validation to life. For centuries, prophets, scientists and artists have been trying to reduce pain with little success because of the many ways in which it is defined – Is it psychological? physiological? or both? Is pain the stimulus that precedes it? The firing up of neurons that succeeds it? Or the tears that accompany it?
My participation in a tiny part of this vast and complicated quest began six months ago. For my PhD, I will be developing an in-vitro model of inflammatory pain as commonly seen in arthritis. Arthritis, an enigmatic disease affecting one in five people globally, is characterised by swollen and painful joints. My goal is to understand how these inflamed joints communicate with the nerves linked to them to cause pain and ultimately to develop treatments. This problem can be approached from the organism, systemic, cellular or molecular level. I will be trying to reduce inflammatory pain using a cell-based model. Although my research is restricted to the cellular level in the peripheral nervous system (the area which does not involve the brain and spinal cord), an overall understanding of the different areas and levels of scientific pain research is essential since the ultimate aim is to bring all these together.
Pain and reward prediction
The recent "Challenges of Chronic Pain” conference held at Wellcome Genome Campus Conference Centre provided one such learning opportunity.
Professor Howard Fields’ keynote lecture gave a clear overview of the behavioral and systemic levels of biology involved and showed how our expectation of a pain treatment affects treatment outcome with regard to both chronic and acute pain. How we predict how the treatment will make us feel mirrors our actual feeling after receiving the treatment, he said. What was fascinating for me was how this pain prediction mechanism seems to work in a similar way and to follow similar pathways in the brain to reward prediction – it moves from a behavioural to a systems level issue. Imagine you train your pet rat by giving it food when it is on a red plate and no food when it is on a blue plate. After a few days, instead of giving food, you raise the temperature of both the plates until it becomes painful. Which plate do you think your rat will stay longer on? You guessed correctly: it will DECIDE to stay longer on the red plate where it EXPECTS to get food (a reward). Despite this knowledge, we are yet to understand how this pain prediction mechanism is linked to how the body responds to pain.
Connecting the different issues involved in pain research would be impossible in the absence of suitable techniques for doing so. Thus, the conference devoted a fair amount of time to discussing the different ways that have been developed for visualising neuronal electrical activity, cell by cell in a live animal. Professor Sten Linnarson of the Karolinska Institutet took this approach one step further when he explained his pioneering single cell RNA sequencing method which he is using to try to classify the nervous system based on the genetic profile of each individual cell, creating an atlas of the nervous system.
Another broader aim of pain research is the development of drugs for pain relief. So it was no surprise that the conference started with a session on “The Clinical Landscape” and ended with one on “Drug Development Targets”. Was this perhaps a conscious effort on the part of the organisers to showcase the cyclical nature of research? Drugs that work in the clinic are taken back to the lab to understand how they work and ultimately to develop better drug targets. As a young researcher venturing into the world of pain research, it was heartening to see examples of scientists and pharmaceutical companies coming together to identify drug targets and propose novel gene therapy to combat pain.
Overall, despite moments of clarity, the conference reinforced the elusive and romantic nature of pain. However, now I feel ready to be a part of this historic quest that extends back to our ancestors, although I know only too well that it may well be a bumpy ride.
*Sampurna Chakrabarti  is doing a PhD in Pharmacology. She attended the Challenges of Chronic Pain conference on 1-3 March with support from my supervisor and the Academic Development Fund of Gates Cambridge Trust. Picture credit: Mask on the façade of the Royal Dramatic Theatre in Stockholm c/o Wikipedia.