Combination of tramadol with minocycline exerted synergistic effects on a rat model of nerve injury-induced neuropathic pain

Xiao Peng Mei, Lei Chen, Wei Wang, Dan Wu, Li Ying Wang, Ting Zhang, Hui Zhang, Li Xian Xu, Yun Qing Li

Research output: Contribution to journalArticle

Abstract

Neuropathic pain is a refractory clinical problem. Certain drugs, such as tramadol, proved useful for the treatment of neuropathic pain by inhibiting the activity of nociceptive neurons. Moreover, studies indicated that suppression or modulation of glial activation could prevent or reverse neuropathic pain, for example with the microglia inhibitor minocycline. However, few present clinical therapeutics focused on both neuronal and glial participation when treating neuropathic pain. Therefore, the present study hypothesized that combination of tramadol with minocycline as neuronal and glial activation inhibitor may exert some synergistic effects on spinal nerve ligation (SNL)-induced neuropathic pain. Intrathecal tramadol or minocycline relieved SNL-induced mechanical allodynia in a dose-dependent manner. SNL-induced spinal dorsal horn Fos or OX42 expression was downregulated by intrathecal tramadol or minocycline. Combination of tramadol with minocycline exerted powerful and synergistic effects on SNL-induced neuropathic pain also in a dose-dependent manner. Moreover, the drug combination enhanced the suppression effects on SNL-induced spinal dorsal horn Fos and OX42 expression, compared to either drug administered alone. These results indicated that combination of tramadol with minocycline could exert synergistic effects on peripheral nerve injury-induced neuropathic pain; thus, a new strategy for treating neuropathic pain by breaking the interaction between neurons and glia bilaterally was also proposed.

Original languageEnglish (US)
Pages (from-to)184-196
Number of pages13
JournalNeuroSignals
Volume21
Issue number3-4
DOIs
StatePublished - May 1 2013
Externally publishedYes

Fingerprint

Tramadol
Minocycline
Neuralgia
Spinal Nerves
Ligation
Wounds and Injuries
Neuroglia
Peripheral Nerve Injuries
Nociceptors
Hyperalgesia
Microglia
Drug Combinations
Pharmaceutical Preparations
Down-Regulation
Neurons
Therapeutics

Keywords

  • Analgesic
  • Antiallodynia
  • Microglia
  • Spinal cord
  • Spinal nerve ligation

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience

Cite this

Combination of tramadol with minocycline exerted synergistic effects on a rat model of nerve injury-induced neuropathic pain. / Mei, Xiao Peng; Chen, Lei; Wang, Wei; Wu, Dan; Wang, Li Ying; Zhang, Ting; Zhang, Hui; Xu, Li Xian; Li, Yun Qing.

In: NeuroSignals, Vol. 21, No. 3-4, 01.05.2013, p. 184-196.

Research output: Contribution to journalArticle

Mei, Xiao Peng ; Chen, Lei ; Wang, Wei ; Wu, Dan ; Wang, Li Ying ; Zhang, Ting ; Zhang, Hui ; Xu, Li Xian ; Li, Yun Qing. / Combination of tramadol with minocycline exerted synergistic effects on a rat model of nerve injury-induced neuropathic pain. In: NeuroSignals. 2013 ; Vol. 21, No. 3-4. pp. 184-196.
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