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, F. Porreca

Research output: Contribution to journalArticle

8 Scopus citations


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
Issue number3
StatePublished - Jan 1 1998


ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this