Botulinum toxin A does not alter capsaicin-induced pain perception in human skin.

A genuine peripheral antinociceptive and anti-inflammatory effect of Botulinum neurotoxin type A (BoNT/A) has been proposed but could not be demonstrated in humans so far. Therefore, 100 mouse units of Botulinum toxin A (Dysport) and placebo were injected in a double blind paradigm in defined skin areas of 50 subjects. At baseline and after 4 and 8 weeks allodynia was induced in the skin areas with capsaicin ointment. Heat and cold pain threshold temperatures were measured with quantitative sensory testing, and threshold intensities upon electrical stimulation with a pain specific surface electrode were determined. No BoNT/A related differences in pain perception were found at any quality. There is neither a direct peripheral antinociceptive effect nor a significant effect against neurogenic inflammation of BoNT/A in humans.

Detection of cardiac right-to-left shunts by contrast-enhanced harmonic carotid duplex sonography.

OBJECTIVE: Paradoxical embolization by cardiac right-to-left shunts (RLS) is increasingly recognized as an important factor for embolic stroke. Contrast-enhanced transcranial Doppler sonography (ce-TCDS) is an established diagnostic tool for RLS detection but is frequently limited because of an inadequate temporal acoustic bone window. The purpose of this study was to determine whether extracranial sonography (ECS) using harmonic frequencies improves detection of RLS. METHODS: Extracranial color duplex sonography using harmonic frequencies enables visualization of even single ultrasound contrast agent microbubbles because of oscillation. Patients with stroke and positive RLS findings on transesophageal echocardiography underwent a simultaneous extracranial and transcranial sonographic examination of the proximal common carotid artery (CCA) and middle cerebral artery (MCA) on the same side. A Valsalva strain was performed for 10 seconds after intravenous bolus injection of a galactose-based nontranspulmonary contrast agent. The B-mode frame sequences of the transverse plane of the CCA obtained by harmonic ECS and the ce-TCDS recordings of high-intensity transient signals from the MCA were analyzed offline. RESULTS: In all patients with RLS, the shunts could be identified by harmonic ECS. A close correlation could be seen between the count of visualized microbubbles in the CCA and the number of high-intensity transient signals detected on ce-TCDS in the ipsilateral MCA. CONCLUSIONS: The results of this study indicate that contrast-enhanced ultrasound harmonic imaging of the CCA using a Valsalva strain might be an optional screening tool for detection of cardiac RLS in patients with insufficient acoustic bone windows.

Transcranial duplex sonography in the detection of patent foramen ovale.

PURPOSE: To determine the sensitivity of contrast material-enhanced transcranial color-coded sonography (c-TCCS) compared with that of contrast-enhanced transesophageal echocardiography (c-TEE) for detection of cardiac right-to-left shunt. MATERIALS AND METHODS: Forty consecutive patients with stroke or transient ischemic attack were admitted to the hospital and were examined by using c-TCCS and c-TEE. High-intensity transient signals (HITS) were counted for 25 seconds after the end of the Valsalva maneuver, and the numbers of HITS were classified in one of four categories (zero HITS, one to 10 HITS, >10 HITS without curtain, and curtain). A statistically significant difference was calculated with the Fisher exact test. RESULTS: HITS were counted in 21 (52%) patients by using c-TCCS and c-TEE. With both tests, no HITS were counted in 15 (38%) patients. In two (5%) patients, no HITS were counted with c-TEE but three HITS in one patient and five HITS in the other were counted with c-TCCS. In two (5%) patients, no HITS were counted with c-TCCS, but a small patent foramen ovale (PFO) was seen at c-TEE. With c-TCCS, the sensitivity was 91% (21 of 23) and the specificity was 88% (15 of 17). In 23 patients examined with c-TCCS, 14 (61%) patients had category 1 PFO; seven (30%) patients, category 2 PFO; and two (9%) patients, category 3 PFO. Mean HITS count in patients with category 1 PFO was 4.4 and that for those with category 2 PFO was 27.6. CONCLUSION: c-TCCS is a sensitive noninvasive method for detecting cardiac right-to-left shunt and is as sensitive as c-TEE.

Botulinum toxin A and the cutaneous nociception in humans: a prospective, double-blind, placebo-controlled, randomized study.

Aside from temporary chemodenervation of skeletal muscle and potential anti-inflammatory effects, a genuine peripheral antinociceptive effect of Botulinum Neurotoxin Type A (BoNT/A) has been suspected. To evaluate the effect of BoNT/A on cutaneous nociception in humans, 50 healthy volunteers received subcutaneous injections of 100 mouse units (MU) BoNT/A (Dysport) and placebo. Both forearms of each subject were treated in a double-blind fashion, one with verum, one with placebo. Heat and cold pain thresholds within the treated skin areas were measured with quantitative sensory testing (QST) and pain thresholds were evaluated with local electrical stimulation (ES). The tests were done before treatment, and after 4 and 8 weeks. No major side effects were noted. All participants completed the study. Heat and cold pain thresholds increased from baseline to week 4 by 1.4 degrees C for verum and by 1.1 degrees C for placebo. From baseline to week 8, the thresholds increased by 2.7 degrees C for verum and by 1.2 degrees C for placebo. Electrically induced pain thresholds shifted from baseline to week 4 by -0.07 mA for verum and by 0.01 mA for placebo. From baseline to week 8, the thresholds increased by 0.10 mA for verum and by 0.11 mA for placebo. None of these differences was statistically significant. The study shows that there is no direct peripheral antinociceptive effect of BoNT/A in humans. The efficacy of BoNT/A in various pain syndromes must be explained by other pathways such as chemodenervation or anti-inflammatory effects.