3,[edicine, U~liversity

:sal horn ana anthe most part, but p a r t o f the gray matter. Laterally,

and

te dorsM horn. L a m i n a t has smatL medium view range in size fi'om 5 #m :< 8 #m to

ii~

i~ • ii

~

240

"

X

\

Fig. 1. Schematic drawing of a hemi:iection of the fifthlumbar segment of the central gray as described by Pexed ~ is shown with surrounding

Lamina 5 extends straight between the medial a n d lateral sides of the dorsal horn. It has fewer cells than laminae 1-4, and more and thicker nerve fibers run through it. In the lateral part of lamina 5, the fiber bundles are large and numerous, giving the section a reticulated appearance. The smallest cells in lamina 5 are about 8 tzm × 10 #m and the largest, 30/zm × 45 ~m. Lamin but is it muc base of the smallest cell 15 ~m. Input from the periphery is distribu s~ze (Fig. 3). The large myelinated fibers enters the dorsa~ born from the medial si, in various laminae~ Small diameter myelinated and non.myelinated fibers enter more directly, with some fibers making initial contactwith lamina 1 cells, Others coutact with substantia ~;elatinosa cells and with cells in deeper layers. In addition to receMng dorsal root input, lamina 1 cells connect with cells that are within tt~e substantiagelaiinosa" of thor~ameand n e i ~ e r i i ~ : s ~ e ~ s i : ~ X 0 ~ of the large (Waldeyer) neu:~'ons of lamina 1 project into ~heitate~lsPinal, -i,---~. At least some of the ceils have long ascending . projections w i t ~ i ~he,:: -~ oral cord t°. Laminae 2 and 3 cells are prima61y short connecting i n t e r n ~ n s : ~ c h form axo-axonaI contacts as well as regular synaptic contacts wifll~ e i e , : ~ e r , : ; i n

241

C

D

Fig~ 2. Sagittal ~ i o n through the dorsal horn showing the patterns of ceils in the first 6 Iaminae. iamina 4 c~lL D: interneur0n of lamina 5. um~es indi~te Rexed!Slaminae. (From Brain Res:, 9 (t968) 32-58.)

~orS:~t a ea ,the ~i:~t~sden some generalities

242

/ 2 P

I

t

5

! i l

5 ¢

s

,f

J

'~-,b ~,%

6

| I

-4

'" g

~pinot~lamic ~'oct

To ipsilaterGi ~pinot'nalomie tfoel'

Fig. 3. Diagrammatic presentation of spinal cord dorsal horn structure and prima~ afferent projection into the cord, Numerals indicate Rexed's laminae. (Courtesy John J. Bonita.)

about structure/function relationships are in vogue. For instance, single unit recordings show that lamina 1 (the thin cap layer of the dorsal horn) and lamina 5 neurons apparently receive the bulk of high-threshold input to the cord from the peripheryZ°,43. Highq afferer bellow escape and tc the), b ( utane superficial structures, as well as to woprioceptive input 62. The suprasegmental input to the dorsal horn produces pro. or postsynaptic facilitation or inhibition, and thereby partially regulates what is projected f ¥ ~ m ~ spinal cord to the brain ~2. Overall, t the processing horn. Stated m inR)rmation re~ integrative processes operative in the dorsal horn of theispi:aal cord, : ~.:

243

I. E

? ~g fie2

With this background, Melzack and Wall a° suggested that general a,-,stheties and centrally acting analgesics might act, at least in part, by modifying sensory information processing at cord !ievel. The postulate was a direct contradiction to the long-held view that clinically u~ed concentrations of the agents had no significant

that led to the 1 intravenously ~rn Cells~ Pentoharge. Cells in

244

SPONTANEOUSACTiViTY

N20

to

4¸

holothone

1% .

i

~ 15

0

2%

30

haloihane 45

60

Minutes

TACTILE

60:

504 ?~'

-40 t.

\

_

STIMULATION

N20

" ~ ~ < h0,0,h0n0

3O

20"

!0-

7

6O Minu~e$ Fig. n~OU, ~

Jong

haloths the resl in a cut str~ctu~ Nmina

hat the hypnotic n in the reticular ion o f synoptic aseous anesthetion). Halothane lg rate of dorsal horn neurons. Halothane often completely suppressed the response to noxioa~ (pinChing) o r i ~ o c u o u s (hair stroking) stimuli in 5-45 rain, the former response being suppressed more rapidly than the latter. Nitrous oxide depressed the response to noxious stimuli by about 50~0, the response to innocuous stimuli by only 20-30 ~o Spontan:eous firing was depressed to rougbIy the same extent as response to innocuou~ stimuli. The depressant effect of h~ lothane was dose-related, i.e., the greater the con~n,:r and the stronger the depression of the cenm~l opriocept~ve units were quite resistant to halothane later made with halothane in de,cerebrate ca~sz°, which ktdicates that thepresence of descending inpa', to thedorsal horn did not modify the spinal effects of this agent. Unlike in the spinal cats, 5owever, N~O caused little deviation from normal discharge rates and firing patterns oI ~orsal horn cells in the decerebrate preparation (Fig. 5). After a brief initial period of rL-~dera~ely reduced activity, cells soon regained most of their ability to fire spontaneously and to increase the rate of discharge when skin hairs were stroked. The investigators did not commem on the response to noxious stimulation. The diffei race between the findings in the spinal versus the decerebrate preparation (notable depression in the former case) ..... activates deovercome i~:s ab:ta et aL 32. I spontaneous ly unchanged. :oup sectioned ably accounts tiffereace that ~ith 100 % 02 during control periods, whereas the other investigators used room air. Kitahata etal. examined the effects of hypervenfilafion (which reputedly raises pain tl~reshetd) an dorsal horn- activity when they studied N20; hypervenfilafion and N~O:~ha.d sirni~ar effects. Later, Taub e t a l . 59 subjected the N~O data to detailed statistical analysis.As:a result; they reiterat~ed that 75 % N~.O does not affect spontaneous actMty of lamina 4cells, but their analysis showed that lamina ~ cell activity, which

TABLE I COMPARISON OF ANESTHETIC COURSE AND 50~,/a NEURAL DEPRESSION

20 mg/kg rhiopent~l

Average duration of

ReCovery of cet:firing

anesthesia in intact cat

~ Spontaneous

Evoked

t l . 0 min

19.9 min.

16'0 min

Ether

:

Blood levels durh~g light anesthesia in intact cat

Blood levels at 50 % depression o f cell fir#lg Spontaneous

Evoked

6.7--9.1 n ~ d

3.8 m M

4.7 m M

Plane 2 anesthesia in man 6.7-17.5 m M

decreased, had an increased mean burst interval, accounted for by an increased interburst interval with maintenance of intraburst interva! duration. The spontaneous activity of lamina 6 cells was increased in rate, and their firing pattern was regularized. While not commenting on how N~O depresses lamina 5 activity, the investigators speculated that NeO may increase lamina 6 activity by removing primary inhibitory effects ot: cutanec.u:; afferents on lamina 6 cells. The effects of halothane (2~), thiopental (10, 20 mg/kg), and either (10, 15, 20 ~) on spinal cord neurons of decerebrate or aecerebrate plus low spinal cats were compared by Heavner and De Jong 2~. All 3 anesthetics tested caused similar changes in neural activity. Spontaneous or evoked activity of about 509/0 of the units superficial to lamina 4 w~ch were probably primary afferent axons was not depressed. On the other hand, activity of only 12 ~o S!ightly fewer ne~F~rons in laminae 4 to the number of neurons depressed in lamina 5 (91 ~). Fifty percent depression of evoked activity correlated roughly with ~ight surgical anesthesia in intact cats (Table I). Units responsive to noxious stimulation and units responding to non-noxious stimulation were similarly affected. Shapovalov 5a noted that pentobarbital, hexobarbital: urethane, and ether all depressed spontaneous electrical discharge of interneurons and motoneurons, but that ~the former were more sensitive than the latter. He suggested that there was extraordinar!ily great individual variation in sensitivity of interneurons to anesthetics, and as ethers have observed, depression of spontaneous activity does not always parallel the effects on afferem evoked activity. getami~e. Recently, the 'dissociative' anesthetics--- agents which seemto confuse the patient's sensorium but do not cause unconsciousness ~ have attrac t ed cons~de,r. ,) aNe interesto One such agent, ketamine, has remarkabk; differential anNgesic actions. It profoundly obtunds pain of cutaneous origin; conversely, pain of visceral origin is barely affec~:edZ