Altered antinociceptive efficacy of tramadol over time in rats with painful peripheral neuropathy

Aldric Hama, Jacqueline Sagen

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Pain due to peripheral nerve injury or disease is a dynamic process, such that the mechanism that underlies it alters over time. Tramadol has been reported to be analgesic in clinical neuropathic pain, with varying levels of efficacy due to a patient population that has had neuropathic pain for a wide range of time. In order to address and examine the issue, the antinociceptive efficacy of tramadol over time was tested in rats with a chronic constriction injury (CCI) of the left sciatic nerve. Rats developed a robust hind paw hypersensitivity to innocuous mechanical stimulation ipsilateral to CCI surgery. Subcutaneous injection of tramadol in rats two weeks after CCI surgery dose-dependently attenuated mechanical hypersensitivity, which was abolished with the μ-opioid receptor antagonist naloxone but not the α2-adrenoceptor antagonist yohimbine. Systemic tramadol also attenuated mechanical hypersensitivity four weeks after CCI surgery, but the efficacy significantly diminished at this time point. In addition, the effect of tramadol at this later time point could be reduced with yohimbine as well as naloxone. These data demonstrate that the efficacy of tramadol depends in part on the duration of nerve injury-evoked nociception, and that its antinociceptive mechanism changes over time. Alteration in antinociceptive mechanism over time may explain the inconsistency in efficacy of this and other analgesic drugs in chronic pain patients.

Original languageEnglish
Pages (from-to)32-37
Number of pages6
JournalEuropean Journal of Pharmacology
Volume559
Issue number1
DOIs
StatePublished - Mar 15 2007

Fingerprint

Tramadol
Peripheral Nervous System Diseases
Constriction
Wounds and Injuries
Hypersensitivity
Yohimbine
Neuralgia
Naloxone
Analgesics
Peripheral Nerve Injuries
Nociception
Narcotic Antagonists
Sciatic Nerve
Subcutaneous Injections
Painful Neuropathy
Chronic Pain
Adrenergic Receptors
Pain
Population

Keywords

  • α-Adrenoceptor
  • μ-Opioid receptor
  • Allodynia
  • Chronic pain
  • Consistency
  • Dynamic process

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Altered antinociceptive efficacy of tramadol over time in rats with painful peripheral neuropathy. / Hama, Aldric; Sagen, Jacqueline.

In: European Journal of Pharmacology, Vol. 559, No. 1, 15.03.2007, p. 32-37.

Research output: Contribution to journalArticle

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