Increased mRNA Expression for the α\u3csub\u3e1\u3c/sub\u3e Subunit of the GABA\u3csub\u3eA\u3c/sub\u3e Receptor Following Nitrous Oxide Exposure in Mice

The mechanisms by which nitrous oxide (N2O) produces physical dependence and withdrawal seizures are not well understood, but both N2O and ethanol exert some of their effects via the GABAA receptor and several lines of evidence indicate that withdrawal from N2O and ethanol may be produced through similar mechanisms. Expression levels of mRNA transcripts encoding several GABAA receptor subunits change with chronic ethanol exposure and, therefore, we hypothesized that N2O exposure would produce changes in mRNA expression for the α1 subunit. Male, Swiss–Webster mice, 10–12 weeks of age, were exposed for 48 h to either room air or a 75%:25% N2O:O2 environment. Brains were sectioned and mRNA for the a subunit was detected by in situ hybridization using an 35S-labelled cRNA probe. N2O exposure produced a significant increase in expression levels of the α1 subunit mRNA in the cingulate cortex, the CA1/2 region of the hippocampus, the dentate gyrus, the subiculum, the medial septum, and the ventral tegmental area. These results lend support to the hypothesis that N2O effects are produced, at least in part, through the GABAA receptor and that N2O produces these effects through actions in the cingulate cortex, hippocampus, ventral tegmental area and medial septum. These results are also further evidence that ethanol and N2O produce dependence and withdrawal through common mechanisms

Conduction Properties Distinguish Unmyelinated Sympathetic Efferent Fibers and Unmyelinated Primary Afferent Fibers in the Monkey

Different classes of unmyelinated nerve fibers appear to exhibit distinct conductive properties. We sought a criterion based on conduction properties for distinguishing sympathetic efferents and unmyelinated, primary afferents in peripheral nerves.In anesthetized monkey, centrifugal or centripetal recordings were made from single unmyelinated nerve fibers in the peroneal or sural nerve, and electrical stimuli were applied to either the sciatic nerve or the cutaneous nerve endings, respectively. In centrifugal recordings, electrical stimulation at the sympathetic chain and dorsal root was used to determine the fiber's origin. In centrifugal recordings, sympathetic fibers exhibited absolute speeding of conduction to a single pair of electrical stimuli separated by 50 ms; the second action potential was conducted faster (0.61 0.16%) than the first unconditioned action potential. This was never observed in primary afferents. Following 2 Hz stimulation (3 min), activity-dependent slowing of conduction in the sympathetics (8.6 0.5%) was greater than in one afferent group (6.7 0.5%) but substantially less than in a second afferent group (29.4 1.9%). In centripetal recordings, most mechanically-insensitive fibers also exhibited absolute speeding to twin pulse stimulation. The subset that did not show this absolute speeding was responsive to chemical stimuli (histamine, capsaicin) and likely consists of mechanically-insensitive afferents. During repetitive twin pulse stimulation, mechanosensitive afferents developed speeding, and speeding in sympathetic fibers increased.The presence of absolute speeding provides a criterion by which sympathetic efferents can be differentiated from primary afferents. The differences in conduction properties between sympathetics and afferents likely reflect differential expression of voltage-sensitive ion channels

Assessment of physical activity of patients with chronic pain

Objectives: To define the key terms and concepts relating physical activity to chronic pain; to provide a brief overview of the various methods of assessment of physical activity; to review the current literature about physical activity and chronic pain; and to identify needs for future research. Materials and Methods: A narrative review based on results of a PubMed search (to May 2011) and the references of recent systematic reviews. Results Many methods exist for measuring physical activity. Movement sensors, such as accelerometers, offer objective assessment of physical activity of patients with chronic pain. It is often assumed that patients who feel disabled and report daily life restrictions due to chronic pain also will be less physically active. Studies that have compared the activity of patients with chronic back pain with that of healthy individuals consistently showed that the relationship of physical activity and severity of pain, as well as the change in activity following interventions, was variable and complex. Conclusions It is important to understand the relationship between physical activity and chronic pain. Future studies should objectively assess not only the pattern and complexity of that relationship but also the interaction with the patient's mood and ability to cope with the pain

Separate Peripheral Pathways for Pruritus in Man

Recent findings suggest that itch produced by intradermal insertion of cowhage spicules in human is histamine independent. Neuronal mechanisms underlying nonhistaminergic itch are poorly understood. To investigate which nerve fibers mediate cowhage induced itch in man, action potentials were recorded from cutaneous C-fibers of the peroneal nerve in healthy volunteers using microneurography. Mechano-responsive and -insensitive C-nociceptors were tested for their responsiveness to cowhage spicules, histamine, and capsaicin. Cowhage spicules induced itching and activated all tested mechano-responsive C-units (24/24, but no mechano-insensitive C-fibers (0/17). Histamine also induced itch, but in contrast to cowhage, it caused lasting activation only in mechano-insensitive units (8/12). In mechano-responsive C-units, histamine caused no or only short and weak responses unrelated to the time course of itching. Capsaicin injections activated four of six mechano-responsive fibers and three of four mechano-insensitive C-fibers. Cowhage and histamine activate distinctly different nonoverlapping populations of C-fibers while inducing similar sensations of itch. We hypothesize that cowhage activates a pathway for itch that originates peripherally from superficial mechano-responsive (polymodal) C-fibers and perhaps other afferent units. It is distinct from the pathway for histamine-mediated pruritus and does not involve the histamine-sensitive mechano-insensitive fibers