Faculty Bibliography

Little is known about the effects of successful treatment on brain function in chronic pain. This study examined changes in pain-evoked brain activation following behavioral extinction training in fibromyalgia patients. Using functional magnetic resonance imaging, brain activation to painful mechanical stimuli applied to the 2nd phalanx of the left 2nd digit (m. flexor digitorum) was assessed in 10 patients with fibromyalgia syndrome (FM) before and after behavioral extinction training. The behavioral treatment significantly reduced interference from pain in the FM patients. Mechanical pain threshold and pain tolerance increased significantly after treatment. Activation in the insula shifted bilaterally from a more anterior site before treatment to a more posterior location after treatment. The pre- to post-treatment reduction in both interference related to pain and pain severity were significantly associated with bilateral activation in pain-evoked activity in the posterior insula, the ipsilateral caudate nucleus/striatum, the contralateral lenticular nucleus, the left thalamus and the primary somatosensory cortex contralateral to the stimulated side. These data show a relation between successful behavioral treatment and higher activation bilaterally in the posterior insula and in the contralateral primary somatosensory cortex. Future studies should compare responders and non-responders for differential treatment effects and examine in more detail the mechanisms underlying these changes.

BACKGROUND: While the etiology of fibromyalgia syndrome (FMS) remains unclear, it is assumed that both peripheral and central components are involved. AIMS/METHODS: To investigate central activation patterns following chemically-induced muscle pain we repetitively injected protons (low pH) and prostaglandin E(2) (PGE(2)) in isotonic solution into the left extensor carpi radialis brevis muscle of female FMS patients and female healthy control subjects (HC). The injection of protons/PGE(2) has the advantage that it is not prone to tachyphylaxis compared to capsaicin and hypotonic saline solution. During the repetitive injections continuous pain ratings were recorded and functional magnetic resonance imaging measurements were conducted. RESULTS: Injection of protons/PGE(2) led to activation of the anterior and medial cingulate cortices, contralateral primary sensory cortex, bilateral insula and thalamus, left basal ganglia, left orbitofrontal cortex and the cerebellum in FMS patients. In HC, activations were found only in the anterior, medial, and posterior cingulate cortices, and the primary somatosensory cortex. The contrast between the groups revealed significantly stronger activation for FMS patients in the left anterior insula. Peak pain ratings were comparable between HC and FMS patients, but pain duration (sustained pain) was prolonged in FM. CONCLUSION: Repetitive proton/PGE(2)-induced excitation of muscle tissue led to a more prolonged perception of pain and more wide-spread activation in pain-related brain areas in FMS, especially in the left (ipsilateral) insula, whereas acute protons/PGE(2)-induced pain processing was similar in the two groups. These data provide further evidence for enhanced central pain processing in FMS patients.

Stress-induced analgesia (SIA) refers to a reduced pain response after stress exposure, which is mediated by descending pain-inhibitory circuits and may be an indicator of adequate centrally mediated pain control. We used functional magnetic resonance imaging to assess brain mechanisms of SIA in 21 healthy participants. Using a block design series of mildly painful pressure stimuli were applied to the left medial phalanx of the second digit during functional magnetic resonance imaging. Mental arithmetic combined with increasing levels of noise was used as a stressor. Verbal ratings, changes in blood pressure and heart rate confirmed the validity of the stress induction. Post-stress pain thresholds and pain tolerance were significantly higher and post-stress pain and unpleasantness ratings were significantly lower compared to pre-stress levels. SIA led to an increase of the blood-level-dependent oxygenation response in the primary somatosensory cortex, bilaterally in the anterior insula, and secondary somatosensory cortex. The increase in pain tolerance correlated significantly with activation in the rostral anterior cingulate cortex and pain unpleasantness with activation in the dorsal anterior cingulate cortex. SIA seems to activate similar brain networks as placebo analgesia or analgesia mediated by diffuse noxious inhibitory controls and involved sensory, affective and cognitive modulatory circuits.