Skin innervation at different depths correlates with small fibre function but not with pain in neuropathic pain patients.

BACKGROUND: Neuropathy can lead not only to impaired function but also to sensory sensitization. We aimed to link reduced skin nerve fibre density in different levels to layer-specific functional impairment in neuropathic pain patients and tried to identify pain-specific functional and structural markers. METHODS: In 12 healthy controls and 36 patients with neuropathic pain, we assessed clinical characteristics, thermal thresholds (quantitative sensory testing) and electrically induced pain and axon reflex erythema. At the most painful sites and at intra-individual control sites, skin biopsies were taken and innervation densities in the different skin layers were assessed. Moreover, neuronal calcitonin gene-related peptide staining was quantified. RESULTS: Perception of warm, cold and heat pain and nerve fibre density were reduced in the painful areas compared with the control sites and with healthy controls. Warm and cold detection thresholds correlated best with epidermal innervation density, whereas heat and cold pain thresholds and axon reflex flare correlated best with dermal innervation density. Clinical pain ratings correlated only with epidermal nerve fibre density (r = 0.38, p < 0.05) and better preserved cold detection thresholds (r = 0.39, p < 0.05), but not with other assessed functional and structural parameters. CONCLUSIONS: Thermal thresholds, axon reflex measurements and assessment of skin innervation density are valuable tools to characterize and quantify peripheral neuropathy and link neuronal function to different layers of the skin. The severity of small fibre neuropathy, however, did not correspond to clinical pain intensity and a specific parameter or pattern that would predict pain intensity in peripheral neuropathy could not be identified.

Cross-over evaluation of electrically induced pain and hyperalgesia.

Background Anewexperimental protocol of electrically induced pain and hyperalgesia was established to examine orally administered drugs. In a randomized, double-blind, placebo-controlled cross-over study this experimental protocol was used to assess the effects of paracetamol. Methods Twenty-four subjects were enrolled in this study. The magnitude of pain, axon reflex flare, and areas of pin-prick hyperalgesia and touch-evoked allodynia were assessed in two consecutive sessions; prior to, and 2 h after drug administration. This protocol was repeated after 1 week. Subjects were randomized to receive either paracetamol (2 g) or a placebo. Results In comparison to the placebo arm there were no significant effects of paracetamol on pain, hyperalgesia, allodynia, or axon reflex flare. Pain and flare responses were highly reproducible on the same day (r = 0.77 and r = 0.79, respectively), and after 1 week (r = 0.6 and r = 0.71, respectively). The correlation between areas of hyperalgesia and allodynia was, however, significantly improved when the protocol was repeated on the same day (r = 0.8 and r = 0.75), as opposed to after a week (r = 0.54 and r = 0.53). Discussion The electrical pain model is a well established method for the assessment of intravenously applied analgesics. In order to assess effects of orally applied drugs the model had to be modified: for the assessment of hyperalgesia and allodynia a protocol repeating the model within 1 day proved to have advantages over repetition after 1 week.

Comparison of electrically induced flare response patterns in human and pig skin.

OBJECTIVE: We compared the characteristics of neurogenic flare responses in human and pig skin to establish a translational research animal model. MATERIAL AND SUBJECTS: Eight domestic pigs and six male subjects were investigated. TREATMENT: Electrical pulses were delivered transcutaneously with increasing current intensities, pulse frequencies and pulse widths. METHODS: Inflammatory skin responses were recorded by laser Doppler imaging and analyzed by ANOVA and Fisher's (LSD) post hoc test. RESULTS: Transcutaneous stimuli of 5 mA onward induced a significant flare development in humans. In the pig, significantly lower currents of 2.5 mA already induced a flare response. Smaller flare sizes of about 3.5 cm(2) were analyzed. The flare continuously declined despite ongoing stimulation. CONCLUSIONS: Lower excitation thresholds and smaller receptive fields of nociceptors can be suggested in pigs. Impaired neuropeptide release, altered vesicle replenishment, different neuropeptide sensitivity, or insufficient peripheral decoding of action potentials may contribute to steadily decreasing flare responses. These attributes may be objectives of pre-clinical anti-hyperalgesic studies and their accurate analysis in pigs reveals a particularly sensitive translational animal model for nociceptor researches.

[Damage of the subclavian vein with a thorax drainage]. / Verletzung der V. subclavia mit einer Thoraxdrainage.

The necessity for insertion of a thorax drainage can lead to serious complications. Especially the use of a trocar instead of a mini-thoracotomy has a notable risk of misplacement or complications. Chest tubes per se can perforate the parietal pleura resulting in an extrathoracic position of the tube and contraindications for chest tubes should always be considered. Accidental lacerations of blood vessels should be avoided by a correct technique and a clear indication. A chest X-ray in one plane is not sufficient to prove correct positioning of a chest tube and suspected misplacement of a chest tube has to be assessed radiographically in at least two planes. A case of a fatal complication of a misplaced chest tube causing a laceration of the right subclavian vein is described.

Continuous brachial plexus blockade in combination with the NMDA receptor antagonist memantine prevents phantom pain in acute traumatic upper limb amputees.

BACKGROUND: Hyperexcitability of N-methyl-d-aspartate acid (NMDA) receptors may play an important role in the development of phantom limb pain (PLP). AIM OF THE STUDY: To investigate whether early treatment with the NMDA antagonist memantine attenuates phantom pain memory formation in traumatic amputees. METHODS: In a randomized, double-blind, controlled trial 19 patients with acute traumatic amputation of the upper extremity were investigated. All patients received postoperative analgesia by continuous brachial plexus anesthesia (ropivacaine 0.375% 5 ml/h) for at least 7 days. In addition, the patients received either memantine (20-30 mg daily, n=10) or placebo (n=9) for 4 weeks. RESULTS: Memantine treatment reduced the number of requested ropivacacine bolus injections during the first week and resulted in a significant decrease of PLP prevalence and intensity at 4 weeks and 6 months follow up, but not at 12 months follow up. CONCLUSIONS: We conclude that memantine can reduce intensity of phantom limb pain and might also prevent the development of PLP. However, despite the very early begin of treatment; no long-term effect on established PLP was evident.

[Ephedrine as alternative to Akrinor in regional obstetric anesthesia]. / Ephedrin als Alternative zu Akrinor in der geburtshilflichen Regionalanästhesie.

Hypotension in anesthesia and obstetric anesthesia in particular, is a widespread problem. After the temporary withdrawal of Akrinor from the market, the internationally available drug ephedrine is available for prevention and therapy of hypotension in anesthesia and its effect is comparable with Akrinor. In obstetric epidural anesthesia the intravenous prophylactic drug application of ephedrine seems to be superior to therapeutic application only. The aim of this overview is to show alternatives to the currently administered catecholamines for prevention of hypotension in obstetric anesthesia.

[Respiratory failure due to delta-9-tetrahydrocannabinol in a tetraplegic patient]. / Respiratorische Insuffizienz durch Delta-9-Tetrahydrocannabinol bei tetraplegischem Patienten.

We report on a patient with an incomplete tetraplegia below C2 who suffered from a post-traumatic abdominal spasticity, spasticity of the legs, and bladder contractions of high intensity. Breathing was possible during the day using accessory respiratory musculature. All standard therapeutic regimes against spasticity failed. Treatment was started with delta-9-tetrahydrocannabinol administered orally in a dosage of 2 x 2.5 mg/day. The spasticity of the legs and the bladder improved with the treatment. After 3 days, the patient complained about dyspnea and shortness of breath. Treatment with delta-9-tetrahydrocannabinol was discontinued after 5 days but the patient needed ventilatory support for 1 week. After 1 week, spontaneous breathing was possible again. The reasons for respiratory failure in endangered patients during treatment with delta-9-tetrahydrocannabinol could be effects such as sedation, combined treatment with baclofen, muscle weakness, or central nervous effects in the medulla oblongata.

Clonidine increases membrane-associated phospholipase A 2.

BACKGROUND AND OBJECTIVE: An anti-inflammatory effect of alpha2-adrenoreceptor agonists has been suggested. Phospholipase A2 is a key enzyme in the production of precursors of inflammatory lipid mediators. The aim of the present study was to investigate the effect of clonidine on phospholipase A2 activity in an established in vitro model. METHODS: Human being platelet membranes containing active phospholipase A2 were exposed to buffer control or to three increasing concentrations of clonidine. Phospholipase A2 was measured by a radioisotope technique. RESULTS: A massive increase in phospholipase A2 activity was measured after clonidine exposure leading to final values of 92.5 +/- 3.1 pmol mg protein(-1) min(-1) (4.5-fold higher than control values; P < or = 0.01 vs. control). After clonidine exposure the maximal reaction velocity increased, while the Michaelis-Menten constant did not change. The Lineweaver-Burk representation suggested an interaction of clonidine with the phospholipase A2-substrate complex as well as the phospholipase A2 molecule. CONCLUSION: We conclude that the putative anti-inflammatory effect of clonidine was not caused by inhibition of phospholipase A2.

[Cannabinoids--signal transduction and mode of action]. / Cannabinoide--Signaltransduktion und Wirkung.

The therapeutic use of cannabinoids, the components of cannabis sativa L., was investigated in numerous researches in detail. Animal studies revealed that cannabinoid receptor agonists alter pain-associated behaviour, have immune-suppressive properties, suppress tumor growth, modulate sensitisation processes and influence memory and learning. Those effects are mediated by two membrane-bound cannabinoid receptors and as mechanisms of signal transduction blockade of ion channels, inhibition of adenylate cyclase and retrograde inhibition of neurotransmitter release are currently being discussed. In clinical studies oral administration of cannabinoids indicated beneficial results during the therapy of multiple sclerosis, weight loss, nausea and vomiting due to chemotherapy, and intractable pruritus. However, therapy of chronic pain conditions revealed conflicting results and unequivocal success could not have been delivered due to unwanted side effects. Further multicentre studies are required to estimate cannabinoids as novel therapeutic tools for the treatment of chronic pain.