Visceral Pain Therapy; Research

visceral pain therapy published

scientists at University Autonoma
Barcelona,
Department
Anaesthesiology

on
by
of
of

ABSTRACT
The abdominal acetic acid-induced writhing test was used to examine the
peripheral, preemptive antinociceptive opioid action onvisceral nociception. HS731 administered subcutaneously (s.c.) or intracerebroventricularly (i.c.v.) dosedependently and completely inhibited writhing, being 24-598-fold more potent,
depending on the administration route, than two selective MOR agonists, the
enkephalin analogue [D-Ala(2),N-Me-Phe(4),Gly-ol(5)]enkephalin (DAMGO) and
morphine.
2007 NOV 26 - (NewsRx.com) -- A new study, 'DAMGO and 6beta- glycine
substituted 14-O-methyloxymorphone but not morphine show peripheral,
preemptive

antinociception

after

systemic

administration

in

mouse visceral pain model and high intrinsic efficacy in the isolated rat vas
deferens,' is now available. "Peripheral micro- opioid receptors (MOR) have
emerged as important components of inhibitory nociceptive pathways. Here,
the antinociceptive effects of MOR agonists, the 6beta-glycine derivative of 14O- methyloxymorphone (HS-731), DAMGO and morphine were evaluated in a
mouse model of visceral pain," scientists writing in the journal Brain Research
Bulletin report.
"The abdominal acetic acid-induced writhing test was used to examine the
peripheral, preemptive antinociceptive opioid action onvisceral nociception. HS731 administered subcutaneously (s.c.) or intracerebroventricularly (i.c.v.) dosedependently and completely inhibited writhing, being 24-598-fold more potent,
depending on the administration route, than two selective MOR agonists, the
enkephalin analogue [D-Ala(2),N-Me-Phe(4),Gly-ol(5)]enkephalin (DAMGO) and
morphine. A longer duration of action (2-3 h) was induced by HS-731 given
before acetic acid, while shorter effect was produced by morphine (30-60 min)

and DAMGO (30-45 min). The antinociceptive effects of systemic opioids were
reversed by the s.c. opioid antagonist, naloxone. Blocking of central MOR by the
selective MOR antagonist D-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH(2) (CTAP, i.c.v.)
resulted in a significant reduction of antinociception of s.c. morphine, whereas it
completely failed to antagonize the effects of systemic HS-731 or DAMGO. In in
vitro studies, HS-731 and DAMGO, but not morphine showed high intrinsic
efficacy, naltrexone-sensitive agonist effect at MOR of the rat vas deferens.
These data demonstrate that selective activation of peripheral MOR by systemic
s.c.

HS-731

or

DAMGO

produces

potent

peripheral,

preemptive visceral antinociception, while morphine's effects are mediated

primarily through central mechanisms," wrote M. Al-Khrasani and colleagues,
Semmelweis University.
The researchers concluded: "Our findings support the role of peripheral MOR in
the pathology of pain states involving sensitization of peripheral nociceptors."
Al-Khrasani and colleagues published their study in Brain Research Bulletin
(DAMGO and 6beta-glycine substituted 14-O- methyloxymorphone but not
morphine

show

peripheral,

preemptive

antinociception

after

systemic

administration in a mouse visceralpain model and high intrinsic efficacy in the

isolated rat vas deferens. Brain Research Bulletin, 2007;74(5):369-75).
Additional information can be obtained by contacting M. Al- Khrasani,
Semmelweis

University,

Dept.

of

Pharmacology

and

Pharmacotherapy,

Budapest, Hungary.
The publisher of the journal Brain Research Bulletin can be contacted at:
Pergamon-Elsevier Science Ltd., the Boulevard, Langford Lane, Kidlington,
Oxford OX5 1GB, England.
Keywords: Hungary, Budapest, Visceral Pain Therapy, Acetic Acid, Analgesic,
Antinociceptive, Brain Research, Drugs, Glycine, Morphine, Narcotic, Neurology,
Opiate Agonist, Opioid Receptors, Pain Medicine, Pharmaceuticals, Therapy,
Treatment, Visceral Pain.
This article was prepared by Pain & Central Nervous System Week editors from
staff and other reports. Copyright 2007, Pain & Central Nervous System Week
via NewsRx.com.

BIBLIOGRAFIA

Visceral pain therapy; data from semmelweis university advance knowledge in visceral pain
therapy. (2007). Pain & Central Nervous System Week, , 224. Retrieved from
http://search.proquest.com/docview/208497249?accountid=36765
OBTENIDO
DE
:
http://search.proquest.com/docview/208497249/2F88CAD2027D484FPQ/3?accountid=36765

Terapia del dolor visceral; La investigacin sobre el

tratamiento del dolor visceral publicado por
cientficos de la Universidad Autnoma de Barcelona,
Departamento de Anestesiologa
Un nuevo estudio, 'DAMGO y glicina sustituido 6beta- 14-Omethyloxymorphone pero no muestra la morfina perifrica antinocicepcin,
de preferencia despus de la administracin sistmica en un modelo de
dolor visceral ratn y alta eficacia intrnseca de los aislados del vaso
deferente de rata,' ya est disponible. "Receptores opioides perifricos
micro (MOR) han surgido como componentes importantes de las vas
nociceptivas inhibidores. Aqu, los efectos antinociceptivos de agonistas
MOR, el derivado 6beta-glicina de methyloxymorphone 14-O- (HS-731), se
evaluaron DAMGO y morfina en un modelo de ratn de dolor visceral, "los
cientficos a escribir en la revista cerebral informe de Research Bulletin.

"Se utiliz el ensayo de retorcimiento inducido por cido actico abdominal

para examinar la accin perifrica, preventivo antinociceptivo opioide sobre
la nocicepcin visceral. HS-731 se administra por va subcutnea (sc) o
intracerebroventricular (icv) dependiendo de la dosis y retorcindose
completamente inhibida, siendo 24-598- veces ms potente, dependiendo
de la va de administracin, de dos agonistas MOR selectivos, el anlogo de
encefalina [D-Ala (2), N-Me-Phe (4), Gly-ol (5)] encefalina (DAMGO) y la
morfina. Una mayor duracin de accin (2-3 h) se indujo por HS-731 se
administra antes del cido actico, mientras que el efecto ms corto fue
producido por la morfina (30-60 min) y DAMGO (30-45 min). Los efectos
antinociceptivos de los opioides sistmicos se invirtieron por el antagonista
sc opioides, naloxona. el bloqueo de MOR central mediante el antagonista
MOR selectiva D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH (2) (CTAP, icv) dio
lugar a una reduccin significativa de la antinocicepcin de morfina sc,

mientras que fracas por completo para antagonizar los efectos de HS-731 o
DAMGO sistmicos. En estudios in vitro, HS-731 y DAMGO, pero no la
morfina mostr alta eficacia intrnseca, efecto agonista naltrexona sensible
al MOR de los conductos deferentes de rata. Estos datos demuestran que la
activacin selectiva de MOR perifrica por s.c. sistmico HS-731 o DAMGO
produce potentes perifrica, antinocicepcin preventiva visceral, mientras
que los efectos de la morfina estn mediados principalmente a travs de los
mecanismos centrales ", escribi M. Al-Khrasani y sus colegas de la
Universidad de Semmelweis.

BIBLIOGRAFIA
Visceral pain therapy; data from semmelweis university advance knowledge in visceral pain
therapy. (2007). Pain & Central Nervous System Week, , 224. Retrieved from
http://search.proquest.com/docview/208497249?accountid=36765
OBTENIDO
DE
:
http://search.proquest.com/docview/208497249/2F88CAD2027D484FPQ/3?accountid=36765