Most BiM readers will be familiar with a body of research indicating that chronic pain is associated with apparent structural changes in the brain. We’ve discussed this issue here at length (see here and here). These findings, principally of reductions in grey matter density across a smattering of brain regions, have led researchers, myself included, to advance a bundle of speculative hypotheses about the possible role of these changes in chronic pain. Maybe these changes represent the abnormal brain type that predisposes folk to develop chronic pain. Or maybe they represent neural degeneration and the damage that ongoing pain imparts on the central nervous system. Perhaps once you’ve got them the brain is changed forever and the pain will never go. But maybe, though this more mundane possibility has received relatively little attention, they are simply unimportant epiphenomena; innocent bystanders who were in the wrong place at the wrong time and now stand falsely accused. Finally, just maybe, they weren’t even at the crime scene at all. Concerns with the analyses commonly used in voxel-based morphometry studies suggest that they may not always be the most reliable witnesses.
A new paper published in PLoS ONE and beautifully open access, extends the findings of a study that Ben Wand has previously blogged about. This study scanned the brains of folk with chronic hip osteoarthritis (OA) before and after total hip replacement and then at periods up to 14 months following surgery. They also scanned some healthy controls matched for age and sex. Hip OA and replacement surgery offers a funky model as it is one of the only instances where an intervention commonly gives rapid and total relief of chronic pain.
This group of patients pre-operatively demonstrated marked grey matter reductions in “usual suspect” areas such as the anterior cingulate and dorsolateral prefrontal cortices. Following the pain group after surgery when their pain was essentially gone, they demonstrated slight and subtle increases in similar areas though these were not particularly statistically robust. Comparing the hip OA group one year post-op to the healthy control group, the initial reductions in density remained.
What does this mean? Researchers initially went looking for these brain changes in patients with chronic pain conditions that are unresponsive to treatment and in which there were already strong suspicions that central mechanisms were at play. Those early findings in chronic back pain and fibromyalgia seemed to offer something confirmatory to hang that “central mechanisms” hat on. That patients with OA, a condition largely explainable through persistent nociceptive drive also demonstrate similar changes suggests that they are not likely to be a cause of, or a risk factor for chronic pain. That these changes remain largely unaffected in patients who achieve an almost total removal of pain hints that they are unlikely to represent a driving mechanism for chronic pain, nor a barrier to effective pain relief.
There are reasonable counter-arguments to consider. Perhaps these changes are more mechanistically important to “centrally driven” pain syndromes, (if indeed it is correct that this is what fibromyalgia and chronic low back pain are). This argument seems unconvincing to me but maybe the recent finding that different pain conditions appear to demonstrate discreet signatures of structural changes offers some indirect support. You might expect that differences in the location of these changes to influence their impact on brain function. I’m not sure.
We should also be careful to ring-fence the implications of these findings. At most they undermine the potential relevance of grey matter density changes in chronic pain, but they don’t impact upon the evidence from other sources suggesting that chronic pain conditions are characterised by abnormal central sensitivity and altered pain processing.
So where does that leave grey matter density changes? We still don’t know what the changes in density actually represent – neural degeneration, decreased cell size, fluid level, blood volume, or none of the above? It’s hard to build a model on an unexplained phenomenon. But regardless, for me they are edging into the “interesting but not awfully important epiphenomena” category. I wouldn’t convict them yet, as there seem to be acres of reasonable doubt.
As well as writing for Body in Mind, Dr Neil O’Connell, (PhD, not MD) is a researcher in the Centre for Research in Rehabilitation, Brunel University, West London, UK. He divides his time between research and training new physiotherapists and previously worked extensively as a musculoskeletal physiotherapist.
He also tweets! @NeilOConnell
Neil’s main research interests are chronic low back pain and chronic pain more broadly with a focus on evidence based practice. He has conducted numerous systematic reviews including some for the Cochrane Collaboration. He also makes a mean Yorkshire pudding despite being a child of Essex.
Rodriguez-Raecke R, Niemeier A, Ihle K, Ruether W, & May A (2013). Structural brain changes in chronic pain reflect probably neither damage nor atrophy. PloS one, 8 (2) PMID: 23405082
Baliki MN, Schnitzer TJ, Bauer WR, & Apkarian AV (2011). Brain morphological signatures for chronic pain. PloS one, 6 (10) PMID: 22022493