Peripheral and central opioid activity in the analgesic potency of morphine in rats

Pharmacological

Research, Vol. 22, Supplement I,1990

PERIPHERAL

AND

POTENCY Catti

T.,

Institute

OF

MORPHINE

Parenti

C.,

of of

-

stress-opioid

(2),

suggests

of

stress-response. been

correlations

or

and

We

now

pain of

investigated

MOR the

and

also

of

neural

Materials

and

kept

at

and

water.

into

the

mals

lateral

given

icv

b)

for

DuPont

(10

significantly five

introduced

restraint (3

h

or

the HA

synthesis

histidine

de-

of

MOR

in

a_n

animals

ip

-

Results

showed

1043~6618/90/2210109-02/$03.00/O

before

enhanced stress

the or

spinal MOR)

Merck acutely,

3 h ani -

others

were

a)

Sharp

placed

included assay(4).

icv

MOR

(20

(HCI)

acute

(a gift

uglrat)

icv

of MOR,

antinociception. reflex albolished

injected

ANOVA.

injection or

.

was by

in saline

Naltrexone

Ronsisvalle)

ip

food

administration,

or

of MOR

to implanted

last

analyzed

potency potentiate

access

experiments

that

were

from

mg/kg).

were

to

the

mg/kg)

g

gift

tail-flick

Prof.G.

analgesic

free

uglrat:

(lo-30 (2

- 170

cannulae

22OC,

the

ip

150

and

(a

All

by

1 h

5 days

at

min.

Data

the

for

kept

mg/kg).

appeared

exposure

HA of

of

h

200 after

(2

discussion inhibited

of 3 h

by or

provided

ip

12/12

a-FMH

60

determined

was

day-treatment

in

mast-cell

brain

polyethylene

dose

were

SA)

of had

and

for

ug/rat)

or

the

rats

(fl -FNA,

and

of

increase in

antagonists

rats

brain.

4’C

(lo-30

ug/rat)

Results

at was

the

icv

fl-funaltrexamine icv

antihista

potentiation

receptor

icv

days,

Some

cages

Analgesia

from

cold-restraint

cycle

at

five

MOR.

injected

an

of

this

evidence

inhibitor

Sprague-Dawley

drugs of

injected

restraint

of by

lacking

inhibition specific

opioid

a dark/light

ventricle

received

controls. was

with

was

of

- Male

Animals

MOR,

plastic

efficacy

mediation

showing rats

(1).

blockade

presented

HA,

of

and

the

,

the

(MOR)

receptor

potentiation

in

a

morphine

(1) to

HA. methods

22OC.

E Dome) before

analgesia

in

previously

effects

rats rats

(HA)

HA

analgesia

the

antagonists

sensitize of

analgesic

(a-FMH),

on

depleted

of

and

MOR

to

histamine

we

opioid

hypophysectomized

injection

by

sensitivity

duration

algesia,

central

opioid

a-fluoromethylhistidine

carboxylase,

in

Pharmacy, Italy.

-

appear

and

of

Catania,

histamine

participation

(3),

between

magnitude

-

affected

reported

ANALGESIC

R.

95125

attenuated

Furthermore,

has

6,

morphine

systemic

possible

THE

Faculty

cold-stress

release, the

Arrigo-Reina

Doria

is or

effects

The

a-FMH

A.

test

IN

Pharmacognosy,

Viale

analgesia

analgesic

(4).

C.,

and

hypophysectomy

ACTIVITY

RATS.

Spadaro

tail-flick

Stress-induced whereas

by

IN

Catania,

words:

minics

OPIOID

Pharmacology

University Key

CENTRAL

cZ-FMH whereas

When

latency stress

in

cold

controls, -analgesia

o 1990 The Italian Pharmacological

Society

0

Pharmacological and

stress-potentiation

of

MOR

antinociception.

with o-FMH, the increased potency of MOR fected by P-FNA (a mu-selective irreversible or by naltrexone confirming that

( an aspecific opioid in rats MOR mediates

with mu-receptors produce analgesia. cause supersensitivity that

HA exerts

In rats resulted opioid

five

day-treated

to be differently receptor antagonist

receptor antagonist) spinal antinociception

af I

(Table 11, thus by interaction

(5) and may interact with central or peripheral sites to The observation that depletion of neural histamine may of opiate receptors to ip or icv MOR, also suggests

a central

Table 1 Effects of BFNA’ U-FMH - pretreated

Research, Vol. 22, Supplement I,1990

and rats.

Saline 0.5 ml MOR 30 mg/kg,ip MOR 30 mg/kg,ip + naltrexone 2 mg/kg,ip MQR 30 mg/kg,ip + fl-FNA 2 mg/kg,ip M0R 10 ug icv MOR 10 ug icv + naltrexone 2 mg/kg,ip MORlOugicv + naltrexone 20 ug icv MQR 10 ug icv + fl-FNA 2 mg/kg,ip MIIR 10 ug icv + fl-FNA lo ug icv

role

as a mediator

naltrexone’

of some opiate/opioid

on morphine

analgesia

saline-treated(a) MPE% (9) 4.6 42.5 19.7

in saline-

or

u-FMH-treated(b) MPE% (9) 7.2 96.3 * vs(a1 46.1

*

39.3 78.1

8.9 100

57

63.4

* ** * vsfa) *

100

62.7 45.8 32

effects.

21.7 *

o injected **p
11.5 20 min

before

** ** morphine.

* p