Wednesday, November 06, 2013

Pain and Relief Signals Muted in Fibromyalgia - MedPage Today

Patients with fibromyalgia showed less activation in brain responses to pain-related "punishment and reward" anticipatory signaling on functional MRI than healthy controls, a small study showed.

Compared with patients with fibromyalgia, controls had significant increases in signaling in the right ventral tegmental area (VTA) while anticipating pain (P<0.01) and a trend for greater signal activation while actually experiencing pain (P=0.059), according to Marco L. Loggia, PhD, of Harvard Medical School, and colleagues.

Controls also had greater decreases in VTA signaling when anticipating relief from pain (P<0.05), suggesting that patients with fibromyalgia experienced blunting of these anticipatory pain and relief responses, the researchers reported online in Arthritis & Rheumatism.

It's becoming widely recognized that fibromyalgia is characterized by heightened sensitivity to pain, most likely because of abnormal central processing of painful stimuli.

However, little is known about how anticipation of pain and relief may contribute to the affective and cognitive aspects of the experience of pain.

"Expectancy and pain-relevant anxiety, in particular, have been shown to shape subsequent perceptual states. Relief from pain, on the other hand, is a positive hedonic experience intrinsically linked to pain," Loggia and colleagues explained.

To explore whether these components of pain might be altered in chronic pain states such as fibromyalgia, the researchers performed functional MRI studies in 31 patients with fibromyalgia and 14 controls, primarily focusing on the VTA and the nucleus accumbens.

These are areas of the brain involved in reward and punishment processing that also have been linked with fibromyalgia on positron emission tomography.

The pain stimulus for each participant was provided by an inflated pressure cuff on the lower leg, which initially was inflated to 60 mm Hg. Pressure then was increased until participants reported a pain rating of at least 50 out of 100.

Color-coded visual cues were used to induce anticipation of pain and relief. Before inflation of the cuff, a black cross was projected into the participant's visual field, changing to green to signal that the painful stimulus was about to begin. With cuff inflation, the cross then became black again.

Then, shortly before the cuff was deflated, the cross turned blue, signaling anticipation of relief from pain.

At each point, participants pushed buttons to report the intensity of pain and the associated unpleasantness. Simultaneous brain responses to anticipation, pain, and anticipation of relief were assessed on MRI.

Patients' mean age was 44, most were women, and symptoms had been present for 12.5 years. Baseline clinical pain intensity was rated as 34.3 on a 100-point scale, and pain unpleasantness was rated at 32.3.

The initial MRI scan assessed the entire brain, and found increased activation in multiple areas with the pain anticipation cue in both patients and controls, including the basal ganglia, thalamus, and the cerebellum. No differences were seen between patients and controls in anticipation of pain or relief in these whole-brain scans, however.

In addition, there were no significant differences for the nucleus accumbens. Only in the VTA region were there significant between-group differences, as seen using blood oxygen level-dependent functional MRI.

Also, responses to anticipation of pain among controls showed a negative correlation with responses in the VTA to anticipation of relief (r = 0.76, P=0.002). That correlation was not seen in patients with fibromyalgia (r = -0.12, P=0.52).

The VTA is intensely dopaminergic, and, while it has conventionally been thought to participate in reward signaling, it also appears to be involved in punishment and aversion signaling.

"Our observation that a region rich in dopaminergic neurons such as the VTA exhibits less reactivity ... is compatible with the results of other studies showing altered dopaminergic neurotransmission in fibromyalgia patients," the researchers wrote.

The finding that patients with fibromyalgia had diminished responses to painful stimuli in so-called reward regions of the brain may help explain the fact that they also don't typically respond to opioid-induced analgesia, the researchers noted.

Among the factors that may further explain the differences in brain activity in patients with fibromyalgia was a reduced level of activity in the midbrain periaqueductal gray, which helps regulate behavioral responses to pain. This suggested that patients also may have a diminished ability to upregulate brain-centered coping mechanisms.

A limitation of the study was a lack of correlating behavioral data.