Effective Treatment of Chronic Low Back Pain in Humans Reverses Abnormal Brain Anatomy and Function | Journal of Neuroscience – Free full-text article – May 2011

Though also not new, this study is a follow up on an earlier post: Brain abnormalities are Consequence Not Cause of pain (2009). The article below contains dozens of links to further information.

Abstract:

Chronic pain is associated with reduced brain gray matter and impaired cognitive ability.

In this longitudinal study, we assessed whether neuroanatomical and functional abnormalities were reversible and dependent on treatment outcomes.

We acquired MRI scans from chronic low back pain (CLBP) patients before (n = 18) and 6 months after (spine surgery or facet joint injections; n = 14) treatment.

In addition, we scanned 16 healthy controls, 10 of which returned 6 months after the first visit.

We performed cortical thickness analysis on structural MRI scans, and subjects performed a cognitive task during the functional MRI

We compared patients and controls, as well as patients before versus after treatment.

After treatment, patients had increased cortical thickness in the left dorsolateral prefrontal cortex (DLPFC), which was thinner before treatment compared with controls. Increased DLPFC thickness correlated with the reduction of both pain and physical disability.

Additionally, increased thickness in

primary motor cortex was associated specifically with reduced physical disability, and

right anterior insula was associated specifically with reduced pain.

Left DLPFC activity during an attention-demanding cognitive task was abnormal before treatment, but normalized following treatment.

These data indicate that functional and structural brain abnormalities—specifically in the left DLPFC—are reversible, suggesting that treating chronic pain can restore normal brain function in humans.

Introduction

Chronic low back pain (CLBP) is the most prevalent form of chronic pain, and it is the most common reason for disability in the working-age population (Rapoport et al., 2004).

CLBP has been associated with abnormal brain anatomy and function.

When compared with pain-free controls, individuals with CLBP have been shown to have reductions in cortical gray matter in the

bilateral dorsolateral prefrontal cortex (DLPFC),

thalamus,

brainstem,

primary somatosensory cortex (S1), and

posterior parietal cortex

(Apkarian et al., 2004b; Schmidt-Wilcke et al., 2006; Buckalew et al., 2008).

In addition to CLBP, cortical abnormalities occur in a wide variety of other chronic pain conditions, such as chronic headache, arthritis, and fibromyalgia (for review, see May, 2008).

Several studies have also indicated abnormal cortical function in people with CLBP (Giesecke et al., 2004; Baliki et al., 2008; Lloyd et al., 2008; Kobayashi et al., 2009; Tagliazucchi et al., 2010).

Evidence from pain neuroimaging and transcranial magnetic stimulation studies has linked the DLPFC to

There is evidence that some people with chronic pain also have cognitive impairment (Kewman et al., 1991; Eccleston, 1995; Lorenz et al., 1997; Park et al., 2001; Dick et al., 2002, 2003;Apkarian et al., 2004a; Harman and Ruyak, 2005; Veldhuijzen et al., 2006; Lee et al., 2010).

Findings from a recent study in healthy individuals suggested that this cognitive impairment could be a result of the demands that pain puts on cognitive brain networks: cognitive load-related activity was enhanced by pain, and even pain alone activated this cognitive network (Seminowicz and Davis, 2007b).

In that study, acute noxious stimuli were administered while healthy subjects performed a task. Here, instead of noxious stimuli, we presumed that the ongoing nature of chronic pain would alter brain activity during cognitive performance.

Thus, we hypothesized that chronic pain would be associated with relatively greater recruitment of the cognitive brain network activated during an attention-demanding task.

We performed a longitudinal anatomical and functional MRI study with CLBP patients and healthy controls to

(1) identify structural and functional differences between controls and patients before treatment,

(2) determine whether these differences were reversed following treatment, and

(3) establish whether these changes were linked to the amount of treatment-related reduction of pain and disability.

Results

CLBP is associated with decreased cortical thickness in multiple brain areas

Treating CLBP leads to increased cortical thickness in the left DLPFC

Recovery of cortical thickness is independent of depression

The extent of thickness increase in left DLPFC and other areas is associated with effectiveness of treatment

CLBP patients have abnormal left DLPFC activation during cognitive challenge, despite normal performance on the task

Discussion

Our findings provide strong evidence that pain-related neuroanatomical and functional changes are reversible with effective treatment.

Furthermore, we have provided evidence for a link between regional brain function and anatomy.

The left DLPFC was thinner and was activated abnormally in patients before treatment relative to controls; after treatment, the same region became thicker and also functioned more similarly to controls on a cognitive task. Previous research has shown altered brain anatomy in chronic pain conditions

Treating CLBP results in increased cortical thickness in left DLPFC.

Recent studies suggest that changes in brain gray matter can occur when pain is eliminated (Obermann et al., 2009; Rodriguez-Raecke et al., 2009; Gwilym et al., 2010). The current study extends those findings to changes in cortical thickness, which is a quantitative measure that can be compared between studies, unlike gray matter density.

Furthermore, we demonstrate that

the left DLPFC got thicker in each CLBP patient who improved after treatment, and that

the amount of neuroanatomical recovery depended on the amount of improvement in clinical outcome measures in each patient.

The patients in our sample received treatment interventions that targeted the presumed pain generators within the musculoskeletal system (i.e., spinal structures).

Thus, it seems that the development of chronic pain can lead to prefrontal cortical thinning, and—from the present results—that reducing pain can lead to prefrontal cortical thickening.

It is also evident that anxiety and depression are closely related to these changes, although in both the case of the rat study and the present study, affective measures alone did not explain the differences in cortical volume or thickness.

The reduction of incoming nociceptive inputs from peripheral structures likely accounts for part of the improvement in pain and pain-related disability.