Visceral Pain Therapy; Research on visceral

pain therapy published by scientists at

University Autonoma of Barcelona,
Department of Anaesthesiology
ABSTRACT

The abdominal acetic acid-induced writhing test was used to examine the peripheral,
preemptive antinociceptive opioid action onvisceral nociception. HS-731 administered
subcutaneously (s.c.) or intracerebroventricularly (i.c.v.) dose-dependently 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 a 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 14-O-
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. HS-731 administered
subcutaneously (s.c.) or intracerebroventricularly (i.c.v.) dose-dependently 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-O-methyloxymorphone 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