124

premeditation

“diminishes

the sustained hyperexcitation

tral nervous system”, our interpretation

of the cen-

of the results is quite differ-

surgery

(Kiss

and Kilian

purity of our methods tion in postoperative

ent. The delayed postoperative

time to request

analgesics and lower total dose of

analgesics in the opiate

treated

group are confounded

We cannot request

analgesics

and lower

pethidine

levels of pre~peratively

measures

gesic consumption) we question

(VAS

pain scores and postoperative

were not significantly

the conclusion

that CNS

different

As part of the anesthetic groups)

received

thiopentone.

2

procedure,

pg/kg

We would

of

possibility that the administration .sim

may have provided

thus prevented

or attenuated

in all patients.

While

fentanyl

(i.e.,

in both

induction attention

nociceptive

with to the Cm-i-

activity and

of CNS sensitization

represents

premeditation

a small dose, the

pre-operatively.

They

2.0 @g/kg

duced central prior

hyperactivity

these prolonged

is many times greater

than that required

central consequences

when administered

to injury. We suggest that both groups of patients

benefited

from pre-emptive

lack of a clinically groups. Further dose of attenuates

analgesia

significant

difference

studies are required

pre-operatively

in outcome

between

to assess the minimum

administered

or prevents the central

may have

and that this may explain

analgesics

consequences

that

of anesthesia, pain-free

IS0 min

period).

It is

the analgesic effect of which is hand,

1980), could still

it remains

unclear

which was administered

as to

to all pathe

minimum

on postoperative

effective

analgesia.

We

do

dose of opiate pretreatment

not

know

and whether

a time

factor is involved. The

significantly

reduced

frequency

after surgery, the delayed pain-free in patients

of demand

period,

pretreated

with

for analgesics

and the lower total dose 50 mg of pethidine

effect of opiate premeditation.

surprising, considering

that 2 pg/kg

all

This effect is

of fentanyl (about 0.15 mg/pa-

tient) has about twice the analgesic potency of 50 mg of pethidine. As we concluded probably

the

administered.

effective

time between

has

the

significantly

The

any influence

support the pre-emptive

to prer’mr

opiate

tients prior to induction of anesthesia (about 30 min presurgery),

of analgesics

stimulus-in-

pethidine.

of 4 h (Jaffe and Martin

of fentanyl,

cite Woolf and Wall’s (1986) paper showing that, in animals, the dose to u~o~~s~ established

time to

after

far analgesics was roughly 590

pethidine,

9 h. On the other

of systemic morphine

required

lack of

premedica-

that the delayed

350 min postoperative

known to last a maximum be active after

question of what the mini-

dose is of opiates administered

administered

and the first demand

of anesthesia,

whether

the

total dose of analgesics

min on average (60 mitt until the induction duration

criticize

could have been due to the clinically still active blood

unlikely that intramuscular

prior to surgicul

of fentanyl

the development

2 pg/kg

to

the readers’

authors themselves raise the unanswered mum effective

prior

a block of central

was dimin-

with pethidine.

all patients

fentanyl

like to draw

for the 2 groups

hyperexcitability

ished only in the group that was premeditated

anal-

authors

the role of opiate

analgesia.

premeditation

on board for some time after the end of surgery. Since the

The

agree with the suggestion

with the fact that this group would have had clinically active levels of main outcome

1992).

in determining

have

been

in our more

paper.

the pre-emptive

pronounced

effect

if fentanyl

had

would

not

been

Thus, we agree with Katz et al.‘s suggestion that both

groups of patients have benefited

twith

and without

from pre-emptive

opiate

premeditation)

*‘may

analgesia”.

of noxious peri-op-

erative events.

References References Kiss, LE.

and

postoperative

Jaffe. J.H. and Martin, Kilian,

M.,

analgesia?

Does A

opiate

premeditation

prospective

study,

Pain,

influence 48 (1992)

l57- 15x.

A.C.

Gilman,

and

Gilman’s

Macmillan, Kiss,

Woolf, C.J. and Wall, P.D., Morphine-sensitive sitive actions of C-fibre

and morphine-insen-

input on the rat spinal cord, Neurosci.

I.E.

W.R.,

the

and

Kilian,

analgesics and antagonists.

and A. Gilman

Pharmacological

New York,

postoperative

Opioid

L.S. Goodman

Basis

(Eds.), of

tn:

Goodman

Therapeutics,

1980, p. 514.

M..

analgesia?

Does A

opiate

premeditation

prospective

study,

influence

Pain,

48 (1992)

357-158.

Lett., 64 (1986) 22l--22s. Jvrin E, Kiss Joel Katz

Mathias

Kilian

Brian P. Kavanagh Alan N. Sandler PAIN

02169

Comments on Gong et al., PAIN, 48 0992) We refer to the paper “Morphine-3-glucuronide PAIN

antagonize

0216X

ventiiatory

morphine-6glucuronide depression

the February Although

Reply to Katz et al. We appreciate

the comments

dealing with premeditation

of Katz et al. regarding

as a tool of pre-emptive

our paper

analgesia in back

by other

in Adelaide

original (April.

in

to have one’s novel experimental

researchers,

it is extremely

disap~int~ng

results are not cited.

We showed in our presentation Pain

and

PAIN.

it is always gratifying

when the published

may functionally antinociception

in the rat” by Gong et al. which appeared

1992 issue of

findings verified

induced

249-255

1990)

at the Vlth and

in our

World paper

Congress on “Morphine-3

125 glucuronide - a potent antagonist of morphine analgesia” published subsequently in Life Sciences, 47 (1990) 579-585, that morphine-3glucuronide administered by the intracerebroventricular (i.c.v.1 route was a functional antagonist of the analgesic effects of i.c.v. morphine and i.c.v. morphine-6-glucuronide. We also reported our observation that i.c.v. M6G (0.5 PLg)produced marked late (with respect to the onset of analgesia) respiratory depression, although we did not quantify this latter observation. We trust that you will bring our prior publication to the attention of your readers. Tess Cramond Maree T. Smith Julie A. Watt

Gong, Q.-L. Hedner, J., Bjorkman, R. and Hedner, T., Morphine-3glucuronide may functionally antagonize morphine-6-glucuronide induced antinociception and ventilatory depression in the rat, Pain, 48 (1992) 249-255. Shimomura, K., Kamata, O., Ueki, S., Oguri, K., Yoshimura, H. and Tsukamoto, H., Analgesic effect of morphine glucuronides, Tohoku J. Exp. Med., 105 (1971) 45-52. Smith, M.T., Watt, J.A. and Cramond, T., Morphine-3-glucuronide a potent antagonist of morphine analgesia, Life Sci., 47 (1990) 579-585. Wahlstrom, A., Winblad, B., Bixo, M. and Rane, A., Human brain metabolism of morphine and naloxone, Pain, 35 (1988) 121-127. Thomas Hedner (on behalf of the authors)

Division of Anaesthetics

The University of Queensland Herston Qld 4029, Australia

PAIN 02170

Reply to Cramond et al. The letter by Cramond et al. is most welcome since it further points out the potential importance of the morphine metabolites when evaluating the pharmacological actions of morphine in the experimental animals as presented by us (Gong et al. 1992) in the February issue of Pain. We certainly recognize their prior publication (Smith et al. 1990) demonstrating that morphine-3-glucuronide in the experimental situation and at some dose-concentration levels may act as a functional antagonist to morphine-6-glucuronide. The excitatory actions of morphine-3-glucuronide, published already 20 years ago (Shimomura et al. 19711, are now well known and confirmed by several authors (see Gong et al. 1991). Indeed, the potential importance of the morphine-3-glucuronide and morphine6-glucuronide metabolites for the analgetic and respiratory effects of morphine have been pointed out in some of this early work. However, although theoretically interesting, the potential clinical importance of the morphine metabolites is not yet settled. Certainly it may be anticipated that when used in the clinic, the dose and route of morphine administration would be of major importance as well as any interindividual differences in drug disposition and potential drug polymorphism (Wahlstrom et al. 1988). Moreover it may also be predicted that the putative clinical actions of morphine-3-glucuronide would be different after acute and chronic administartion of morphine since it is logical to assume that tolerance would develop for morphine and morphine-6-glucuronide through their actions on the mu opioid receptor but not for morphine-3-glucuronide which acts through non-opioid mechanisms (see Gong et al. 1991). In obvious agreement with Cramond et al. we hope that future experimental and clinical work will explore further details the on pharmacological profile of morphine and its known metabolites.

References Gong, Q.-L., Hedner, T., Hedner, J., Bjiirkman, R. and Nordberg, G., Antinociceptive and ventilatory effects of the morphine metabolites: morphine-3-glucuronide and morphine-6-glucuronide, Eur. J. Pharmacol., 193 (1991) 47-56.

Department of Clinical Pharmacolqgy Sohlgrenska University Hospital S-413 45 GBtehorg, Sweden

PAIN 02172

Comments on Swerdlow and Dieter, PAIN, 48 (1992) 205-213 In light of the current re-examination of thermography as a diagnostic imaging tool (Medical news and perspectives, JAMA, 287 (1992) 1885-1887) I feel it is necessary to respond to the recent paper by Swerdlow and Dieter (PAIN, 48 (1992) 205-213). Most researchers and clinicians acknowledge that thermography visualizes skin surface temperature, which is essentially a reflection of cutaneous blood flow regulated by the autonomic nervous system and other factors. The criticism of thermography is not a debate over what is imaged but how that information is interpreted and used in diagnosis. The paper by Swerdlow and Dieter purports to show the inadequacies of thermography in diagnosis of trigger points while it displays the same lack of understanding of technique and physiology which is so often criticized when it appears in pro-thermography publications. I cite 3 examples of the errors evident in the paper. (1) Swerdlow and Dieter’s protocol involves first finding myofascial trigger points by palpation, followed by thermal imaging one or more days later. This procedure defies logic! Trigger points, or incipient trigger points, or any physiological mechanism which might produce local hyperemia, may increase or decrease its thermal manifestations over time. It could be expected that pressure applied to a myofascial irritation might resolve the condition over succeeding days, resulting in loss of any thermal signal which might have been present. On the other hand, pressure applied to a specific anatomic site may initiate physiological responses that could become hyperemit over the next several hours or days, even though it was asymptomatic to the original pressure/irritation. It should have been easy for Swerdlow and Dieter to obtain thermograms of their subjects first, before any physical examination, followed immediately by the examination for trigger points. Such a technique would have obviated any criticism of physical trauma affecting the thermogram. This is the procedure that is recommended in most thermographic protocols. (2) In their description of their protocol the authors indicate that the definition of a hot spot associated with a trigger point was 1°C warmer than the circumambient temperature. However, in their figures and text they do not make measurements but rather observe changes in color! They do not seem to recognize that the transition