Treatment-related changes in brain activation in patients with fibromyalgia syndrome.

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.

Differential central pain processing following repetitive intramuscular proton/prostaglandin E2 injections in female fibromyalgia patients and healthy controls.

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.

Long-acting local anesthetics attenuate FMLP-induced acute lung injury in rats.

BACKGROUND: Endothelin-1 (ET-1) is a mediator of lung diseases and a potent pulmonary vasoconstrictor. In addition to thromboxane A2, it participates in the formation of lung edema. Both lidocaine and mepivacaine attenuate the increase of pulmonary arterial pressure (PAP) and lung edema development. We examined the effects of procaine, bupivacaine, and ropivacaine on experimentally evoked PAP increase and ET-1 release. METHODS: PAP and lung weight were measured in isolated rat lungs during perfusion with Krebs-Henseleit hydroxyethyl starch buffer. Bupivacaine, ropivacaine, or procaine was added to the solution at concentrations of 10(-2)-10(-7) mg/kg. ET-1 levels were measured in the perfusate by enzyme-immunoassay, and thromboxane A2 levels were assayed by radioimmunoassay. N-formyl-L-leucine-methionyl-L-phenylalanine was used to activate human polymorphonuclear neutrophils. RESULTS: Bupivacaine, ropivacaine, and procaine significantly attenuated increases of PAP (P < 0.05) and resulted in a reduction of lung weight in these treatment groups compared with the sham group (P < 0.05). The long-acting anesthetics bupivacaine and ropivacaine (P < 0.05), but not procaine, reduced ET-1 levels, produced low inflammation rates, and did not affect lung structures at doses from 10(-3) to 10(-6) mg/kg. CONCLUSION: Bupivacaine and ropivacaine attenuated N-formyl-L-leucine-methionyl-L-phenylalanine-induced PAP, reduced lung edema, and diminished ET-1 release. Lidocaine and mepivacaine are more effective in reducing PAP and edema formation, but long-acting local anesthetics also inhibit ET-1 depletion and therefore have increased anti-inflammatory properties.

Painful and nonpainful phantom and stump sensations in acute traumatic amputees.

BACKGROUND: The formation, prevalence, intensity, course, and predisposing factors of phantom limb pain were investigated to determine possible mechanisms of the origin of phantom limb pain in traumatic upper limb amputees. METHODS: Ninety-six upper limb amputees participated in the study. A questionnaire assessed the following question: side, date, extension, and cause of amputation; preamputation pain; and presence or absence of phantom pain, phantom and stump sensations or stump pain or both. RESULTS: The response rate was 84%. Sixty-five (81%) participants returned the questionnaire. In 64 (98.5%) participants a traumatic injury led to amputation; the amputation was necessary because of infection in one patient (1.5%). The median follow-up time (from amputation to evaluation) was 3.2 years (range, 0.9-3.8 years) The prevalence of phantom pain was 44.6%, phantom sensation 53.8%, stump pain 61.5%, and stump sensation 78.5%. After its first appearance, phantom pain had a decreasing course in 14 (48.2%) of 29 amputees, was stable in 11 (37.9%) amputees, and worsened in 2 (6.9%) of 29 amputees. Stump pain had a decreasing course in 19 (47.5%) of 40 amputees but was stable in 12 (30%) amputees. Phantom pain occurred immediately after amputation in 8 (28%) of 29 amputees between 1 month and 12 months in 3 (10%) amputees and after 12 or more months in 12 (41%) amputees. CONCLUSION: Stump pain and stump sensation predominate traumatic amputees' somatosensory experience immediately after amputation; phantom pain and phantom sensations are often long-term consequences of amputation. Amputees experience phantom sensations and phantom pain within 1 month after amputation, a second peak occurs 12 months after amputation. Revised diagnostic criteria for phantom pain are proposed on the basis of these data.