Assessment of regional analgesia in clinical practice and research

Assessment of pain and sensory function during regional analgesia contributes to a better understanding of the mechanisms underlying the action of drugs and techniques, and provides information on the effectiveness of regional analgesia in daily practice. Sensory tests only partially mimic clinical pain, mainly because they are artificial and reproduce only a part of the complex experience of pain. Therefore information gained by sensory tests should not be uncritically generalized to clinical pain conditions. Studies using experimental pain models are not in competition with studies performed under clinical conditions, but complement them. In order to mirror clinical pain, experimental models ideally stimulate muscles and viscera, induce peripheral and central sensitization, and evoke temporal and spatial summation. These methods are available, but are underused. Test modalities used in clinical practice have limited validity. In recent years almost no research has been performed to develop better test modalities that are suitable for daily practic

Xenon does not reduce opioid requirement for orthopedic surgery

Purpose: Is to test the hypothesis that 70% xenon has a relevant opioid sparing effect compared to a minimum alveolar concentration (MAC)-equivalent combination of N2O and desflurane. Methods: In this randomized, controlled study of 30 patients undergoing major orthopedic surgery we determined the plasma alfentanil concentration required to suppress response to skin incision in 50% of patients (Cp50) anesthetized with xenon (70%) or a combination of N2O (70%) and desflurane (2%). A response was defined as movement, pressor response > 15 mmHg, heart rate > 90 beats · min−1, autonomic reactions or a combination of these. At skin incision, alfentanil was administered at a randomly selected target plasma concentration thereafter the concentration was increased or decreased according to the patient's response. After skin incision, desflurane was adjusted to maintain the bispectral index below 60 and prevent responsiveness in both groups. Results: The Cp50 (± standard error) of alfentanil was 83 ± 48 ng · mL−1 with xenon and 49 ± 26 ng · mL−1 with N2O/desflurane (P = 0.451). During surgery five xenon and 15 N2O/desflurane patients were given desflurane at 1.0 ± 0.5 volume % and 2.5 ± 0.7 volume %. The total age adjusted MAC was 0.97 ± 0.07 and 0.94 ± 0.07 respectively (P = 0.217). The intraoperative plasma alfentanil concentrations were 95 ± 80 and 93 ± 60 ng · mL−1 respectively (mean ± SD;P = 0.451). Patients given xenon were slightly more bradycardic, whereas blood pressure was similar. Conclusion: Xenon compared to a MAC-equivalent combination of N2O and desflurane does not substantially reduce opioid requirement for orthopedic surgery. A small but clinically irrelevant difference cannot be excluded, howeve

Central hypersensitivity in chronic pain: mechanisms and clinical implications

The available literature consistently shows increased pain sensitivity after sensory stimulation of healthy tissues in patients who have various chronic pain conditions. This indicates a state of hypersensitivity of the CNS that amplifies the nociceptive input arising from damaged tissues. Experimental data indicate that central hypersensitivity is probably induced primarily by nociceptive input arising from a diseased tissue. In patients, imbalance of descending modulatory systems connected with psychologic distress may play a role. There is experimental support in animal studies for the persistence of central hypersensitivity after complete resolution of tissue damage. This is particularly true for neuropathic pain conditions, whereby potentially irreversible plasticity changes of the CNS have been documented in animal studies. Whether such changes are present in musculoskeletal pain states is at present uncertain. Despite the likely importance of central hypersensitivity in the pathophysiology of chronic pain, this mechanism should not be used to justify the lack of understanding on the anatomic origin of the pain complaints in several pain syndromes, which is mostly due to limitations of the available diagnostic tools. Treatment strategies for central hypersensitivity in patients have been investigated mostly in neuropathic pain states. Possible therapy modalities for central hypersensitivity in chronic pain of musculoskeletal origin are largely unexplored. The limited evidence available and everyday practice show, at best, modest efficacy of the available treatment modalities for central hypersensitivity. The gap between basic knowledge and clinical benefits remains large and should stimulate further intensive research

Development and pharmacokinetic characterization of pulmonal and intravenous delta-9-tetrahydrocannabinol (THC) in humans

The aim of the present study was to develop a physiologically compatible inhalation solution of delta-9-tetrahydrocannabinol (THC), and to compare the pharmacokinetic and analgesic properties of pulmonal THC versus pulmonal placebo and intravenous (iv) THC, respectively. Eight healthy volunteers were included in this randomized, double-blind, crossover study. The aqueous THC formulations were prepared by using a solubilization technique. iv THC (0.053 mg/kg body weight), pulmonal THC (0.053 mg/kg), or a placebo inhalation solution was administered as single dose. At defined time points, blood samples were collected, and somatic and psychotropic side effects as well as vital functions monitored. An ice water immersion test was performed to measure analgesia. Using a pressure-driven nebulizer, the pulmonal administration of the THC liquid aerosol resulted in high THC peak plasma levels within minutes. The bioavailability of the pulmonal THC was 28.7 +/- 8.2% (mean +/- SEM). The side effects observed after pulmonal THC were coughing and slight irritation of the upper respiratory tract, very mild psychotropic symptoms, and headache. The side effects after iv THC were much more prominent. Neither pulmonal nor iv THC significantly reduced experimentally induced pain