Dear Robert,
Nice reply. I will have to check out some of your references: I find it
interesting that you suggest that anesthetics may act directly at the
somatosensory cortex. I do intrinsic signal optical imaging of the
rat somatosensory (barrel) cortex, and our lab has found that there is no
difference in the functional representation of a stimulated whisker in
rats under either Nembutal or Urethane anesthesia (we haven't tried others;
unpublished results). I also find very little difference between a deeply
anesthetized rat's representation and a lightly anesthetized rat's
represesntation.
Thus my experience suggests that anesthesia is probably not acting via
the primary somatosensory. But the previous statement needs many
qualifications which I cannot go into right now, so I should read your
papers to see how you reached your conclusion...
On 30 May 1996, Robert Arnott wrote:
> I am not sure that it is possible to attribute a pharmacological basis for
> the anaesthetic action of urethane or, indeed, any other general
> anaesthetic agent at this time.
> Early experiments by Meyer (1899) and Overton (1901) showed a high degree
> of correlation between an agent's lipid solubility and its anaesthetic
> potency, suggesting that perturbation of the phospholipid membrane is
> important in anaesthetic action Subsequent experiments have suggested the
> pressure-reversibility of general anaesthesia (for example Lever et al.,
> 1971; Halsey & Wardley-Smith, 1975). More recent experiments by Franks &
> Lieb (1988, 1994) have suggested that anaesthetic may act primarily by
> altering the behaviour of ion channels within the cell membrane.
> Work in our department has concentrated on the effects of general
> anaesthetics on the behaviour of one of the afferent pathways, the dorsal
> column medial lemniscal pathway, in vivo. Results from these studies
> (see, for example, Angel 1991) have suggested that anaesthetics may have
> either the thalamic relay nucleus (in our experiments ventroposterolateral
> thalamus) or primary somatosensory cortex as their site of action in
> modulating the afferent transmission of somatosensory information and in
> modulating cortical arousal. There is also the suggestion that the
> thalamic reticular nucleus or spontaneously active cortical cells may also
> have a role in modulating afferent transmission and may thus be an
> important locus for anaesthetic action since they show
> anaesthetic-dependant changes in discharge behaviour.
> Very recent work (Angel & Arnott, 1994; Arnott & Angel, 1996) looking at
> the effects of the anaesthetic agent Etomidate has suggested that the site
> in the dorsal column pathway which appears to be altered by both agents
> such as urethane, halothane, ether etc. and Etomidate is the cortex, rather
> than the thalamus. We suggest that it may be that it is this common site
> of action which is important in determining the efficacy of anaesthetics in
> modulating afferent transmission.
> Of course one must ask various, as yet unanswered questions. Maybe,
> amongst others, one could consider the following:
> If general anaesthetics exert their effects by altering the behaviour of
> ion channels, how do they do this? What components of primary
> somatosensory cortex are altered in their behaviour by general
> anaesthetics? What is the normal physiological function of these
> structures, so how might changes in their behaviour be important? Do
> anaeshetics simply alter levels of cortical arousal (and, if so, how?) or
> do they have a more specific, site-dependent action? Why is it that the
> short-latency responsiveness of a particular group of cells (eg thalamic
> VPL cells) may be altered by some anaesthetics but not by others, and yet
> the cells to which VPL projects (lamina IV and VI CoSI cells) appear to be
> affected by all agents?
> I would recommend that you read Angel's (1991) review which covers a lot of
> the work in the field. Please let me know if I can be of further help.
[References snipped]
> Best wishes,
> Robert Arnott,
> Centre for Research in Anaesthetic Mechanisms,
> Department of Biomedical Science,
> The University of Sheffield,
> SHEFFIELD.
> S10 2TN
> England
> email r.h.arnott at sheffield.ac.uk> Telephone +44114 276 8555 ext. 4660
> Fax +44114 276 5413
> URL http://www.shef.ac.uk/uni/academic/A-C/amrc/
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-Neal Prakash
Department of Psychobiology, College of Medicine
http://meded.med.uci.edu:80/~nprakash/neal.html
lab:714-824-5031
fax:714-824-2447