Can we prevent declines in brain function and mental health in chronic pain?

15 Jun 2015  |  Print

Can we prevent declines in brain function and mental health in chronic pain?

It seems obvious that chronic pain can negatively affect mental health. However, proving this causal link is not easy. Furthermore, is it unclear whether changes in brain anatomy underlie the association between pain and mental health, or most importantly, whether anything can be done to prevent it. We examine these issues below.

Chronic pain and comorbidities

Comorbidities relating to mental health, such as memory deficits and anxiety/depression, can be devastating for chronic pain patients.[1]

However, does chronic pain cause these comorbidities? Or, rather, do the comorbidities pre-dispose people to develop chronic pain?

This question of cause and effect is difficult to answer based on human studies. However, important work with animal models has suggested that chronic pain can precede mental health issues, and may therefore be the cause of these comorbidities.[2,3]

For example, recent work examined this link using a rat model of neuropathic pain.[2] It was based on ‘spared nerve injury’ (SNI), in which the sciatic nerve was cut and the rats therefore developed hypersensitivity of the affected paw. Anxiety behaviors were then tracked for several months. Over the first few weeks, the injured animals showed no significant increases in anxiety relative to controls, despite their pain. However, by week 20, they showed significantly greater anxiety than control animals.[2] This suggests a temporal relationship in which the chronic pain came first, followed many weeks later by the anxiety.

The same also seems to apply with memory deficits. Again using the SNI model of chronic pain, rats were tested at 6 months post-injury based on a ‘novel object recognition test’, in which one object within the rats’ environment was suddenly changed.[3] Whereas control animals paid increased attention to the new object, the rats with chronic pain did not. This implied that the pain rats did not remember how their environment had previously looked – and hence were not curious about the new object.

Of course, we must be careful when extrapolating animal behavior to human beings. However, the rat studies do suggest that chronic pain may lead to mental health disturbances.

Prevention of comorbidities in chronic pain patients

The work with rat models raises an important clinical question: can we break the link between pain and comorbidities?

In other words, could changes in lifestyle and environment, such as exercise, stress reduction and weight control, prevent the development of mental health problems in chronic pain patients? Evidence from human studies suggests that they might.

For example, yoga is often used to improve painful conditions. In a recent study, people who regularly practiced yoga tolerated pain for more than twice as long as matched controls.[4]

However, to better understand whether lifestyle changes can prevent the deterioration of mental health, we must again turn to animal studies.

In a rat model of chronic pain, animals with experimentally induced inflammatory arthritis were divided into groups according to whether they were allowed to exercise or not, and whether they had food restrictions or not.[5] Levels of the stress hormone, corticosterone, where found to be highest in arthritic rats that had no access to exercise and had unlimited amounts of food. Giving the rats exercise or controlling their diet was associated with reduced stress hormone levels; doing both together – giving the rats exercise and controlling their diet – was associated with the lowest levels of stress hormones.[5]

Furthermore, animals that were able to exercise and had a controlled diet also suffered less pain than those with no exercise and unlimited food.[5]

Hence, simple lifestyle improvements relating to diet and exercise improved pain and reduced the stress associated with chronic pain. If the same were true in humans, we might also expect reductions in stress-related mental comorbidities.

Chronic pain and brain anatomy

Chronic pain and the brain's anatomy

Chronic pain can have profound effects not just on comorbidities but also on brain anatomy. For example, chronic low back pain has been linked with decreased cortical thickness.[6] Meanwhile, chronic pain patients may also experience accelerated age-related losses in gray matter relative to healthy individuals.[7,8]

However, as with the link between chronic pain and comorbidities, it is difficult to determine from human studies whether chronic pain is the cause or the effect of the brain changes. Again, animal models may provide important answers.

In an MRI study of rats, chronic neuropathic pain was associated with decreased frontal cortex volume relative to controls.[2] These changes only became statistically significant several months after the injury, suggesting that the chronic pain may have caused the changes in brain anatomy.

Can we reverse these changes through lifestyle modification?

Animal experiments suggest that this may indeed be possible. For example, in a rat SNI model of neuropathic pain, animals given access to an enriched environment (a running wheel and other stimuli) showed reductions in levels of pro-nociceptive neuropeptides in the lumbar spine relative to animals kept in an impoverished environment.[9]

Furthermore, in a human study, physical activity (yoga) was linked with increased gray matter in multiple brain regions.[4] These increases correlated with yoga experience, suggesting a possible causal relationship between physical activity and brain morphology.

Conclusions

Chronic pain may both alter the anatomy of the brain and pre-dispose patients to mental health-related comorbidities. Lifestyle factors, such as physical activity and dietary changes, could be important in preventing or reversing these effects.

Much work remains to be done to better elucidate these associations. However, in the meantime, chronic pain patients should be encouraged to make healthy lifestyle choices.

References:

  1. 1. Dersh J, Polatin PB, Gatchel RJ. Chronic pain and psychopathology: research findings and theoretical considerations. Psychosom Med 2002;64:773-786.
  2. 2. Seminowicz DA, Laferriere AL, Millecamps M, et al. MRI structural brain changes associated with sensory and emotional function in a rat model of long-term neuropathic pain. Neuroimage 2009;47:1007-1014.
  3. 3. Low LA, Millecamps M, Seminowicz DA, et al. Nerve injury causes long-term attentional deficits in rats. Neurosci Lett 2012;529:103-107.
  4. 4. Villemure C, Ceko M, Cotton VA, Bushnell MC. Insular cortex mediates increased pain tolerance in yoga practitioners. Cereb Cortex 2014;24:2732-2740.
  5. 5. Pitcher MH, Rauf IZ, Bushnell MC. Annual meeting of the Society for Neuroscience. 15-19 November 2014. Washington DC, USA. Poster JJ29.
  6. 6. Seminowicz DA, Wideman TH, Naso L, et al. Effective treatment of chronic low back pain in humans reverses abnormal brain anatomy and function. J Neurosci 2011;31:7540-7550.
  7. 7. Kuchinad A, Schweinhardt P, Seminowicz DA, et al. Accelerated brain gray matter loss in fibromyalgia patients: premature aging of the brain? J Neurosci 2007;27:4004-4007.
  8. 8. Moayedi M, Weissman-Fogel I, Salomons TV, et al. Abnormal gray matter aging in chronic pain patients. Brain Res 2012;1456:82-93.
  9. 9. Vachon P, Millecamps M, Low L, et al. Alleviation of chronic neuropathic pain by environmental enrichment in mice well after the establishment of chronic pain. Behav Brain Funct 2013;9:22.

 

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