Tramadol and its enantiomers differentially suppress c-fos-like immunoreactivity in rat brain and spinal cord following acute noxious stimulus

C. J. Kovelowski, R. B. Raffa, Frank Porreca

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Tramadol hydrochloride, (1RS,2RS)-2-[(dimethylamino)methyl]-1-(3- methoxyphenyl)-cyclohexanol hydrochloride, is an orally-active, centrally- acting analgesic with a putative dual mechanism of action, including an opioid and non-opioid component. The analgesic properties of tramadol and the possible co-existence of dual mechanisms has been postulated to be due to complementary and interactive pharmacologies of its enantiomers. We examined the ability of tramadol, its enantiomers, and morphine as reference to suppress c-fos-like immunoreactivity (c-fos-ir) in rat spinal cord and brain regions following a noxious stimulus (i.p. administration of 3.5% acetic acid). c-fos-ir was measured by immunocytochemistry and the stained cells in each region were counted 2 h after the acetic-acid injection (2.25 h after tramadol or morphine). Equi-analgesic doses of s.c. morphine (10 mg/kg) or tramadol (30 mg/kg) significantly suppressed c-fos-ir in all areas examined, except dorsal central gray of the spinal cord. The enantiomers of tramadol had distinctive patterns of suppression, neither one suppressed c-fos-ir in all of the regions, and hence neither one alone accounted for the suppression produced by the racemate. These findings support differential and complementary effects of tramadol enantiomers in sub-populations of spinal and supraspinal nociceptive neurons, consistent with the proposed antinociceptive interaction between the enantiomers.

Original languageEnglish (US)
Pages (from-to)211-219
Number of pages9
JournalEuropean Journal of Pain
Volume2
Issue number3
DOIs
StatePublished - 1998

Fingerprint

Tramadol
Spinal Cord
Brain
Morphine
Analgesics
Acetic Acid
Nociceptors
Opioid Analgesics
Immunohistochemistry
Pharmacology
Injections
Population

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Neurology
  • Neuropsychology and Physiological Psychology

Cite this

Tramadol and its enantiomers differentially suppress c-fos-like immunoreactivity in rat brain and spinal cord following acute noxious stimulus. / Kovelowski, C. J.; Raffa, R. B.; Porreca, Frank.

In: European Journal of Pain, Vol. 2, No. 3, 1998, p. 211-219.

Research output: Contribution to journalArticle

@article{7658a4dd93ab430e9df503b17bffc26f,
title = "Tramadol and its enantiomers differentially suppress c-fos-like immunoreactivity in rat brain and spinal cord following acute noxious stimulus",
abstract = "Tramadol hydrochloride, (1RS,2RS)-2-[(dimethylamino)methyl]-1-(3- methoxyphenyl)-cyclohexanol hydrochloride, is an orally-active, centrally- acting analgesic with a putative dual mechanism of action, including an opioid and non-opioid component. The analgesic properties of tramadol and the possible co-existence of dual mechanisms has been postulated to be due to complementary and interactive pharmacologies of its enantiomers. We examined the ability of tramadol, its enantiomers, and morphine as reference to suppress c-fos-like immunoreactivity (c-fos-ir) in rat spinal cord and brain regions following a noxious stimulus (i.p. administration of 3.5{\%} acetic acid). c-fos-ir was measured by immunocytochemistry and the stained cells in each region were counted 2 h after the acetic-acid injection (2.25 h after tramadol or morphine). Equi-analgesic doses of s.c. morphine (10 mg/kg) or tramadol (30 mg/kg) significantly suppressed c-fos-ir in all areas examined, except dorsal central gray of the spinal cord. The enantiomers of tramadol had distinctive patterns of suppression, neither one suppressed c-fos-ir in all of the regions, and hence neither one alone accounted for the suppression produced by the racemate. These findings support differential and complementary effects of tramadol enantiomers in sub-populations of spinal and supraspinal nociceptive neurons, consistent with the proposed antinociceptive interaction between the enantiomers.",
author = "Kovelowski, {C. J.} and Raffa, {R. B.} and Frank Porreca",
year = "1998",
doi = "10.1016/S1090-3801(98)90017-9",
language = "English (US)",
volume = "2",
pages = "211--219",
journal = "European Journal of Pain",
issn = "1090-3801",
publisher = "W.B. Saunders Ltd",
number = "3",

}

TY - JOUR

T1 - Tramadol and its enantiomers differentially suppress c-fos-like immunoreactivity in rat brain and spinal cord following acute noxious stimulus

AU - Kovelowski, C. J.

AU - Raffa, R. B.

AU - Porreca, Frank

PY - 1998

Y1 - 1998

N2 - Tramadol hydrochloride, (1RS,2RS)-2-[(dimethylamino)methyl]-1-(3- methoxyphenyl)-cyclohexanol hydrochloride, is an orally-active, centrally- acting analgesic with a putative dual mechanism of action, including an opioid and non-opioid component. The analgesic properties of tramadol and the possible co-existence of dual mechanisms has been postulated to be due to complementary and interactive pharmacologies of its enantiomers. We examined the ability of tramadol, its enantiomers, and morphine as reference to suppress c-fos-like immunoreactivity (c-fos-ir) in rat spinal cord and brain regions following a noxious stimulus (i.p. administration of 3.5% acetic acid). c-fos-ir was measured by immunocytochemistry and the stained cells in each region were counted 2 h after the acetic-acid injection (2.25 h after tramadol or morphine). Equi-analgesic doses of s.c. morphine (10 mg/kg) or tramadol (30 mg/kg) significantly suppressed c-fos-ir in all areas examined, except dorsal central gray of the spinal cord. The enantiomers of tramadol had distinctive patterns of suppression, neither one suppressed c-fos-ir in all of the regions, and hence neither one alone accounted for the suppression produced by the racemate. These findings support differential and complementary effects of tramadol enantiomers in sub-populations of spinal and supraspinal nociceptive neurons, consistent with the proposed antinociceptive interaction between the enantiomers.

AB - Tramadol hydrochloride, (1RS,2RS)-2-[(dimethylamino)methyl]-1-(3- methoxyphenyl)-cyclohexanol hydrochloride, is an orally-active, centrally- acting analgesic with a putative dual mechanism of action, including an opioid and non-opioid component. The analgesic properties of tramadol and the possible co-existence of dual mechanisms has been postulated to be due to complementary and interactive pharmacologies of its enantiomers. We examined the ability of tramadol, its enantiomers, and morphine as reference to suppress c-fos-like immunoreactivity (c-fos-ir) in rat spinal cord and brain regions following a noxious stimulus (i.p. administration of 3.5% acetic acid). c-fos-ir was measured by immunocytochemistry and the stained cells in each region were counted 2 h after the acetic-acid injection (2.25 h after tramadol or morphine). Equi-analgesic doses of s.c. morphine (10 mg/kg) or tramadol (30 mg/kg) significantly suppressed c-fos-ir in all areas examined, except dorsal central gray of the spinal cord. The enantiomers of tramadol had distinctive patterns of suppression, neither one suppressed c-fos-ir in all of the regions, and hence neither one alone accounted for the suppression produced by the racemate. These findings support differential and complementary effects of tramadol enantiomers in sub-populations of spinal and supraspinal nociceptive neurons, consistent with the proposed antinociceptive interaction between the enantiomers.

UR - http://www.scopus.com/inward/record.url?scp=0031708930&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031708930&partnerID=8YFLogxK

U2 - 10.1016/S1090-3801(98)90017-9

DO - 10.1016/S1090-3801(98)90017-9

M3 - Article

C2 - 15102381

AN - SCOPUS:0031708930

VL - 2

SP - 211

EP - 219

JO - European Journal of Pain

JF - European Journal of Pain

SN - 1090-3801

IS - 3

ER -