Treat the pain, mend your brain?

Living with chronic pain can be miserable. Not only are there the nagging aches and pains of every day life, but there might also be forgetfulness, anxiety, depression, or difficulty concentrating as well.

Researchers don’t yet know whether these ‘cognitive deficits’ are caused by pain itself, or whether it’s naturally more forgetful, anxious, depressed or concentration-lacking people who are predisposed to developing some form of chronic pain.

This is where animal studies come in handy to dissociate cause and effect. We recently published a study [1] where rats were given a sciatic nerve injury, and their touch and temperature sensitivity, plus anxiety-like behavior, measured before surgery and followed over 6 months – equivalent to many years of a human lifespan, and much longer than other animal studies investigating pain and cognition. To investigate how cognition was affected, after six months animals did a ‘novel object recognition’ test [2], to see if the rats’ attentional abilities were still intact.

Over 6 months, we saw that the animals remained very sensitive to touch and cold, much as people who suffer from neuropathic pain do if you poke them or expose their skin to the cold.  We also saw ‘anxiety-like’ behaviors – on a raised plus-shaped platform with 2 open and 2 closed arms, animals spent more time ‘safe’ in the closed arms than exploring the exposed arms (a behavior that can be reversed with anxiolytics), unlike ‘sham’-operated control animals. Therefore we could conclude that it was the pain causing the anxiety.

Importantly, we also saw that our animals had problems with attention, much like many chronic pain sufferers.  For a few minutes per day for 3 days, rats had been allowed to explore a large box with 4 objects stuck to the walls. The objects were all exactly the same (size, color, texture and smell) except for their shape. On the 4th day, one of these was replaced with a new shape – for example, a circle was replaced with a square. When animals notice the new object, they spend more time exploring it – which is exactly what we saw in the control animals. However, the rats with the injured nerves spent no more than chance amounts of time sniffing the new object, suggesting they hadn’t noticed the switch.

These results are useful for researchers, as it not only shows that the cognitive problems which go along with chronic pain can be modeled in animals, but also that it’s the pain causing these problems. Finally, this suggests (with some recent evidence to back it up [3]) that if the pain can be treated, then maybe the cognitive impairments could improve too. Good news for anxious and forgetful back pain sufferers!

About Lucie Low

Lucie Low biog pic 150x150 Treat the pain, mend your brain?Lucie is a postdoctoral researcher at the National Center for Complementary and Alternative Medicine, at the National Institutes of Health in Bethesda, MD, USA. When not drinking vast amounts of British tea (shipped from her homeland especially), she’s interested in how chronic pain affects cognition, where her socks disappear to in the laundry, and skydiving.

References

[1] Low LA, Millecamps M, Seminowicz DA, Naso L, Thompson SJ, Stone LS, & Bushnell MC (2012). Nerve injury causes long-term attentional deficits in rats. Neuroscience letters, 529 (2), 103-7 PMID: 22999928

[2] Millecamps M, Etienne M, Jourdan D, Eschalier A, & Ardid D (2004). Decrease in non-selective, non-sustained attention induced by a chronic visceral inflammatory state as a new pain evaluation in rats. Pain, 109 (3), 214-24 PMID: 15157681

[3] Seminowicz DA, Wideman TH, Naso L, Hatami-Khoroushahi Z, Fallatah S, Ware MA, Jarzem P, Bushnell MC, Shir Y, Ouellet JA, & Stone LS (2011). Effective treatment of chronic low back pain in humans reverses abnormal brain anatomy and function. Journal of neuroscience, 31 (20), 7540-50 PMID: 21593339

Comments

  1. “if the pain can be treated, then maybe the cognitive impairments could improve too”

    With Chronic and lasting pain, many patients have been cognitively impaired for a longer period of time. What soft of lasting effects would this have even once the pain is treated?

    [Reply]

    Lucie Reply:

    Hi Julian,

    We hope that, in future, human research will give us the answer. We think that treating the pain will help reverse some of the cognitive impairments, or slow their onset at least.

    [Reply]

  2. Peggy Heinselman says:

    Thank You so much for clearing up some of the mental pain surrounding the misery of being trapped inside a body constantly in pain. I know from studies that physical pain can originate in the mind. Likewise I was not surprized to have my physical pain cause the ‘cognitive deficits’ taking place in my brain. It is my ONE system experiencing the pain. Is the term ‘chronic pain’ used when there is no physical cause that can be found for the pain, or is it also used when you have very visable reasons for constant physical pain? I guess I am wondering why there would even be a question as to the congnitive deficits you mentioned, happening to a person living with constant pain and the losses in one’s quality of life due to the limitations it puts on your every move, the side effects of medication, and the dwindleing basic exuberance for life? I would question my mental faculities if I did not respond to physical unending pain with depression, anxiety, forgetfulness and at it’s worse, suisidal thoughts. I am sure you put those rats out of their misery when the tests where completed. If you did, you understand, empathetically what chronic pain is. If you didn’t, you would be sadistic, and you would not be in this field if you were that, of course. I do know that if my spinal cord could be repaired, or severed completely, and I felt no pain, I would be absolutely free of these cognitive deficits, even if it meant I was confined in a wheel chair! But, I am a human, not a rat, and there is not a neurosurgeon to be found who will sever an intact spinal cord, even tho it is flattened like a ribbon and being compressed less severely in two more areas in my cervical spine. The only good prognosis is, someday, I will wear through my own mylin and become paralyzed. My accident occurred when I was 10 years old, I am 63 at present and my last pain free day was 53 years ago. I cannot believe how tough that thin sheath of mylin is around ones spinal cord!! But then again I have modified my life to relieve the pain which, as pain was meant to do, protects me from farther damage. At 10 years of age I do not know if I was predisposed to depression, anxiety or brain fog/forgetfulness, but can tell you that chronic pain is a vehicle big enough to carry every one of those and more to my brain. On a happier note, for the past two years I have been prescribed Medical Marijuana and it has been the best pain suppressor so far, plus when not in so much pain, I have been thinking, feeling, sleeping and remembering better then I have in decades!! If I had only known!!

    [Reply]

    Lucie Reply:

    Hi Peggy,

    Glad you got something out of the blog post, and the medical marijuana is helping you now. We do euthanize animals at the end of experiments, and we also take their brain tissue – this tissue is invaluable in telling us what changes the pain has caused at a cellular and molecular level, in a way that is impossible to do in humans.

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  3. Thank you.

    This makes perfect sense to me. I wish these studies could be done without causing pain to animals – I hate for anyone to go through what so many of us already do.
    But thank you, this fits my world.

    [Reply]

  4. These findings can not be generalised to humans,therefore what is the point of experimenting with rats?
    How much pain were they in?

    [Reply]

    Lucie Reply:

    Hi Karen,

    The reason we did this experiment is precisely because the findings CAN be generalised to humans – they can suffer the exact same issues in attention that we saw with these rats. The point of using rats is that, once the experiment is done, we can investigate exactly what’s going on with neurons and proteins in the brain at a molecular level that is just not possible in humans. This can help us work out HOW the neurons have changed, and WHY it’s affecting behavior in both rats and humans. This gives us vital information about how the brain cells are firing, and what drugs or treatments might be help reduce pain.

    The pain model we used here is a nerve injury model – it leaves the animals slightly motor-impaired, but they can still run around, and they eat, sleep and play very normally. They show hypersensitivity to touch and heat though, much like humans suffering from peripheral neuropathies (i.e. diabetes or HIV-associated neuropathy).

    [Reply]

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