Mark Hutchinson – Glial cells, opioids and immunity

He promised to rock our immunoneuropharmacology world, and by the number of conversations his talk generated, Professor Mark Hutchinson certainly lived up to his promise.

How do you know you are sick, and how do your patients know? Your mood, capacity for cognitive thought and ability to enjoy things all change. How can your gut change your brain unless they are connected? With rather more than a nod to the alternative practitioners, he showed us the dichotomous view of the body, of either a garden or the machine, and concluded that both models were correct, and that Western medicine has aspects which have not been anticipated. According to Hutchinson, we experience illness as an active process that has nervous, humoural and cellular components, all migrating into parts of the brain.

Many of the studies in this exploding field are only possible now because of the new technologies such as genetic manipulation and in vivo imaging techniques. Basically, the neurological system is not the straight line wiring system, but is an integral part of the immune system.

He took us on an academic roller-coaster ride through the role of the glial cells. Classically, the nervous system was viewed as linear, with only the neurones with their 1014 synaptic connections being functional. Named after the Greek word for glue, the glial cells are now shown to be immunologically based, and are regulators of synaptic activity of the brain, not just its architectural framework. Astrocytes communicate nociceptive signals, but the microglia originate from the immune system. So only studying the neurones is “like looking at the bike paths of Eastern Europe to describe the global transport infrastructure,” Professor Hutchinson said.

Changing an emotion for 20 minutes is enough to alter your immune system, and the immune system can be modified via behavioural, or Pavlovian, conditioning. In studies using rats and medical students, a novel taste of strawberries and lavender (equivalent to ringing the bell in Pavlov’s experiments) was paired with cyclosporine A (the food), to cause immunosuppression (salivation in the early study). Researchers found that an immunological response could be seen several days later just by giving the novel taste again.

New MRI studies of the brain show the same activity from thinking about pain as actually experiencing it, demonstrating the emotional component of pain. Pain medication acts as a pain switch for the neuropharmacology of the pain, but not all analgesics will remove the emotional component, meaning that you are only treating half of the problem.

Hutchinson’s group has developed a revolutionary model of graded sciatic nerve injury, that as well as being a more sensitive experimental model, also has the welfare advantage of inflicting less pain in pain experiments. Their pain response curve can also distinguish pain levels in male versus female, including the differences through the oestrus cycle. They found that transferring just 10,000 microglia from female to male brains could mimic female pain in the males, showing that the glial cells were responsible.

His team found that the expression of approximately 600 genes changed in proportion to amount of pain, of which 300 were “master molecular switches”, and 450 were immune related. As he said, “How can we expect one drug to switch off all of them?”

They were able to show a significant difference in the levels of serum interleukin-β (IL-β), between patients with or without chronic pain, suggesting that IL-β could be a biomarker for the presence of peripheral disease.

He also gave us a tantalising glimpse of the evidence for using nerve blocks rather than opioids in surgery. Single dose opioid causes tolerance, and so if opioids are given intraoperatively, they may be ineffective in the postoperative period. However, giving a simple nerve block intraoperatively does not have that effect, so opioids can be given postoperatively if needed.

I was amazed to hear that although links between the immune system and the brain have been studied for decades, extraordinary new discoveries are now being made. For example, the lymphatic drainage system in the brain was only discovered in 2015.

His skill as a speaker was in alternating high level science with accessible one-liners to illustrate his points. He should be an inspiration to any speaker who still thinks that reading from lecture notes is a good way to engage an audience.

Anne Jackson
Editor in Chief

This article appeared in the July 2016 issue of the Australian Veterinary Journal

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