Group II metabotropic glutamate receptor antagonism prevents the antiallodynic effects of R-isovaline.

We previously showed that isovaline is a peripheral analgesic which acts in vivo and in brain slices as an atypical metabotropic GABA(B) agonist. Peripheral inhibitory group II and III metabotropic glutamate receptors (mGluRs) belong to the same family C as GABA(B) receptors; therefore, we hypothesized that isovaline's analgesic effects could include their activation. We examined the effects of R-isovaline on mechanical allodynia produced by prostaglandin E2 in the mouse paw. Subcutaneous R-isovaline produced dose-dependent antiallodynia restricted to the injected hindlimb. This antiallodynia was blocked by co-injection with a selective group II mGluR antagonist, LY341495, but not a group III mGluR antagonist (MAP-4). The antiallodynic effect of R-isovaline was potentiated by co-administration of a group II mGluR-positive allosteric modulator, LY487379. Injection of a group II mGluR agonist (LY354740) produced an antiallodynic effect which was completely reversed by group II antagonism, but was not affected by group III or GABA(B) (CGP35348) antagonism. Similarly, group II mGluR antagonism did not alter the antiallodynia produced by the prototypical GABA(B) agonist, baclofen. Hence, there was no apparent crosstalk between group II mGluRs and GABA(B) receptors. Previous studies have demonstrated that peripheral GABA(B) receptor activation by isovaline produces antiallodynia. In addition, the present results indicate that activation of peripheral group II mGluRs by R-isovaline produces antiallodynia.

GABA(B) receptor-mediated selective peripheral analgesia by the non-proteinogenic amino acid, isovaline.

Peripherally restricted analgesics are desirable to avoid central nervous system (CNS) side effects of opioids. Nonsteroidal anti-inflammatory drugs produce peripheral analgesia but have significant toxicity. GABA(B) receptors represent peripheral targets for analgesia but selective GABA(B) agonists like baclofen cross the blood-brain barrier. Recently, we found that the CNS-impermeant amino acid, isovaline, produces analgesia without apparent CNS effects. On observing that isovaline has GABA(B) activity in brain slices, we examined the hypothesis that isovaline produces peripheral analgesia mediated by GABA(B) receptors. We compared the peripheral analgesic and CNS effect profiles of isovaline, baclofen, and GABA (a CNS-impermeant, unselective GABA(B) agonist). All three amino acids attenuated allodynia induced by prostaglandin E2 injection into the mouse hindpaw and tested with von Frey filaments. The antiallodynic actions of isovaline, baclofen, and GABA were blocked by the GABA(B) antagonist, CGP52432, and potentiated by the GABA(B) modulator, CGP7930. We measured Behavioural Hyperactivity Scores and temperature change as indicators of GABAergic action in the CNS. ED(95) doses of isovaline and GABA produced no CNS effects while baclofen produced substantial sedation and hypothermia. In a mouse model of osteoarthritis, isovaline restored performance during forced exercise to baseline values. Immunohistochemical staining of cutaneous layers of the analgesic test site demonstrated co-localization of GABA(B1) and GABA(B2) receptor subunits on fine nerve endings and keratinocytes. Isovaline represents a new class of peripherally restricted analgesics without CNS effects, mediated by cutaneous GABA(B) receptors.

Autonomic nervous system response to vibrating and electrical stimuli on the forearm and wrist.

In today's operating rooms, anesthesiologists use physiological data monitoring systems with visual and auditory cues to receive patient information. The efficacy of these visual-audio systems is limited by the human limitations of these modalities. Previous studies have shown the potential use of a complementary, or alternate, patient data monitoring technology utilizing another psychophysically relevant modality: the sense of touch via vibro-tactile or electro-tactile stimulation. In this paper, we describe an experiment designed to determine whether the specific type and/or location of such a tactile stimulation device on the arm affects the autonomic nervous system response. In our study, each of 10 participants tested a vibro-tactile display on the forearm (VF), a vibro-tactile display on the wrist (VW), and an electro-tactile display on the forearm (EF) in random order. Using the LifeShirt, system, electrocardiogram (ECG), respiratory rate (Br), tidal volume (Vt) data were collected. Results showed a higher value of the heart rate and heart rate variability (HRV) when using the VF compared to the VW and EF. We also found that the HRV response for the three tactile prototypes was correlated with the accuracy of tactile pattern identification.

Evaluations of tactile displays of physiological monitoring.

Physiological monitoring devices are used in the operating room (OR) to identify abnormal changes. They are currently detected by the anesthesiologist from direct observation of visual displays or by auditory cues. In an effort to improve OR safety, we explored the use of an alternative sensory modality, touch, to effectively and accurately convey patients' physiological information. To be accepted [1] such devices need to fulfill five criteria: learnability, errors, efficiency, memorability and satisfaction. We designed and compared various tactile displays in respect to some of these criteria.

Evaluation of a tactile display around the waist for physiological monitoring under different clinical workload conditions.

In this study, we have assessed the usability of a tactile belt prototype for clinical monitoring of physiologic patient data in the operating room under low workload (LW) and high workload (HW) conditions. In previous investigations, we have evaluated tactile technology in clinical settings and demonstrated that anesthesiologists have enhanced situational awareness towards adverse clinical events when a tactile display prototype is used as a supplemental monitoring device. To further evaluate the effectiveness of our tactile belt prototype, we compared the effects of workload on the performance of anesthesiologists in terms of accuracy and response time in tactile alert identification. We also administered a post-study questionnaire to evaluate the usability of the tactile belt as well as users' opinions about the device. We found that the response time to tactile alert identification to be faster under LW than under HW, however the accuracy of identification was not statistically different. Participants rated the tactile belt prototype as comfortable to use and the tactile alert scheme as easy to learn. Our findings further support the feasibility and efficacy of vibrotactile devices for enhancing physiological monitoring of patients in clinical environments.

Optimizing the tactile display of physiological information: vibro-tactile vs. electro-tactile stimulation, and forearm or wrist location.

Anesthesiologists use physiological data monitoring systems with visual and auditory displays of information to monitor patients in the operating room (OR). The efficacy of visual-audio systems may impose an increase in patient risk when the demand for constant switching of attention between the patient and the visual monitoring system is high. This is evidenced by auditory alarms frequently being neglected in a noisy OR environment. Hence, the use of a complementary patient data monitoring system, which utilizes other sensory modalities, could be of great value. In this paper, we describe a series of experiments designed to determine the performances of a tactile display that could be used to convey patient's physiological information to the attending anesthesiologist. We tested both vibro-tactile and electro-tactile display prototypes in their ability to convey information using an alert scheme of four distinct tactile stimuli. Using pseudo-clinical data, the display was designed, for example, to provide an alert when a change in the monitored heart rate occurred. Based on previous research in human physiology and psychophysics, we selected the forearm and wrist of the user's non-dominant hand as the stimulation site. In our study of 30 subjects, we evaluated the response time and accuracy of tactile pattern recognition to compare (1) the performance of a vibro-tactile display on the forearm (VF) and an electro-tactile display on the forearm (EF), and (2) the localization of stimulation between the forearm (VF) and a vibro-tactile display on the wrist (VW). A post-study questionnaire was completed by each subject to assess the comfort and usability of the three prototypes. We found that both VF and VW were superior to the EF in both accuracy and comfort and, that there were no differences between the wrist and the forearm. In conclusion, the tactile-display prototypes designed to alert the clinician of adverse changes in a patient's physiological state efficaciously and unobtrusively delivered these data and warranted further investigation and development.

Percussion pacing--an almost forgotten procedure for haemodynamically unstable bradycardias? A report of three case studies and review of the literature.

More than 80 years after its first description by Eduard Schott, percussion (fist) pacing remains a little known procedure even though it represents an instantly available and easy to perform treatment for temporary emergency cardiac pacing in haemodynamically unstable bradycardias, including bradycardic pulseless electrical activity and complete heart block with ventricular asystole. Based on the Consensus on Science and Treatment Recommendations of the International Liaison Committee on Resuscitation, the European Resuscitation Council recently incorporated percussion pacing in its advanced life support guidelines (Nolan and colleagues, Resuscitation 67 (Suppl 1): S39-S86, 2005). Here, we briefly describe three of our own cases and present a review of the literature on percussion pacing with respect to the available evidence on its efficacy, its practical application, and clinical indications.