Tuesday, April 20, 2010

Acute Pain May Hijack the Limbic Brain

Pain and the Great Brain Robbery! Part 2

Various transformations have been found in the brains of persons with chronic pain, including abnormal chemistry, regional gray matter atrophy, cognitive changes, and unique patterns of brain activity. Now research suggests that acute pain episodes may alter the function of critical limbic brain regions to affect the development chronic back pain.

Researchers at Northwestern University, Chicago, imaged the brains of 16 healthy adults and 16 patients with chronic back pain using functional MRI (fMRI) while administering a series of different painful heat stimuli [Baliki et al. 2010]. During fMRI imaging, the brain activity while heat was being applied and the associated pain reported from it were similar between groups. However, healthy individuals showed significantly higher activity in a limbic-brain region called the nucleus accumbens [see illustration] as the thermal heat was decreasing and the pain was coming to an end (pain offset) compared with chronic pain patients (p<0.0001). This difference during offset of the pain distinguished the two groups with 100% sensitivity and 100% specificity, "implying that this signal can be used as an objective marker of chronic pain," the researchers reported in the April 15, 2010 issue of Neuron.

There also were differences between the two groups in how nucleus accumbens activity during the pain-stimuli offset period was reflected in other brain regions. In patients with chronic back pain the nucleus accumbens was most strongly connected with activity in the medial prefrontal cortex — a brain area implicated in valuation, action selection, and pain modulation [see path of arrow in the illustration]. During the experiment, the acute pain stimulus strongly reduced the level of chronic pain perceived (p<0.004), but its end or offset unexpectedly resulted in a worsening of ongoing chronic back pain. In other words, although removal of a painful sensation normally would be expected to register as a reward, among patients with chronic pain it actually appeared to signal a punishment. The researchers called this a "dysfunctional associative learning process," that may be involved in the transition from acute back pain to chronic back pain.

COMMENTS: As is common in brain-imaging studies the number of subjects was small, the interpretation of results can be complex, and further research would be helpful for a more complete understanding. Our earlier blogpost [here] noted that the limbic system plays a pivotal role in pain signaling, processing, and emotional valuation. The nucleus accumbens is at the center of what is called the “mesolimbic reward pathway,” along with the ventral tegmental area and prefrontal cortex. Together, these structures serve as a “rheostat of reward,” cranking-up or toning-down perceptions of reward (eg, pleasure) or punishment (eg, pain).

In this study by Baliki and colleagues, an acute pain stimulus reduced the perception of background chronic pain; however, the offset or relief of acute pain had a reverse effect of being perceived as a punishment rather than reward; “telling” the brain that the chronic pain was worse. This altered and distorted internal state is "an integral component of the pathophysiology of chronic pain," the researchers believe. As a side point, it is interesting to note that alterations in the mesolimbic reward pathway also are at the core of addiction, whether to drugs or nondrug addictive behaviors. [A future weblog entry will discuss the interface of pain and addiction in this regard.]

In a sense, repeated acute pain episodes may hijack vital limbic structures in the brain and alter their function, thereby inducing chronic pain as a brain disease. From a clinical perspective, insights from this study suggest that unless acute back pain episodes are aggressively treated at the outset there could be a greater risk of developing a chronic nonspecific back pain condition that is difficult to reverse.

REFERENCE: Baliki MN, Geha PY, Fields HL, Apkarian AV. Predicting value of pain and analgesia: Nucleus accumbens response to noxious stimuli changes in the presence of chronic pain. Neuron. 2010; 66: 149-160 [article here].