Microglia: A promising target for treating neuropathic and postoperative pain, and morphine tolerance

Yeong-Ray Wen, Ping Heng Tan, Jen Kun Cheng, Yen Chin Liu, Ru Rong Ji

Research output: Contribution to journalReview article

123 Citations (Scopus)

Abstract

Management of chronic pain, such as nerve-injury-induced neuropathic pain associated with diabetic neuropathy, viral infection, and cancer, is a real clinical challenge. Major surgeries, such as breast and thoracic surgery, leg amputation, and coronary artery bypass surgery, also lead to chronic pain in 10-50% of individuals after acute postoperative pain, partly due to surgery-induced nerve injury. Current treatments mainly focus on blocking neurotransmission in the pain pathway and have only resulted in limited success. Ironically, chronic opioid exposure might lead to paradoxical pain. Development of effective therapeutic strategies requires a better understanding of cellular mechanisms underlying the pathogenesis of neuropathic pain. Progress in pain research points to an important role of microglial cells in the development of chronic pain. Spinal cord microglia are strongly activated after nerve injury, surgical incision, and chronic opioid exposure. Increasing evidence suggests that, under all these conditions, the activated microglia not only exhibit increased expression of microglial markers CD11b and Iba1, but also display elevated phosphorylation of p38 mitogen-activated protein kinase. Inhibition of spinal cord p38 has been shown to attenuate neuropathic and postoperative pain, as well as morphine-induced antinociceptive tolerance. Activation of p38 in spinal microglia results in increased synthesis and release of the neurotrophin brain-derived neurotrophic factor and the proinflammatory cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α. These microglia-released mediators can powerfully modulate spinal cord synaptic transmission, leading to increased excitability of dorsal horn neurons, that is, central sensitization, partly via suppressing inhibitory synaptic transmission. Here, we review studies that support the pronociceptive role of microglia in conditions of neuropathic and postoperative pain and opioid tolerance. We conclude that targeting microglial signaling might lead to more effective treatments for devastating chronic pain after diabetic neuropathy, viral infection, cancer, and major surgeries, partly via improving the analgesic efficacy of opioids.

Original languageEnglish
Pages (from-to)487-494
Number of pages8
JournalJournal of the Formosan Medical Association
Volume110
Issue number8
DOIs
Publication statusPublished - Aug 2011
Externally publishedYes

Fingerprint

Microglia
Neuralgia
Postoperative Pain
Morphine
Chronic Pain
Opioid Analgesics
Synaptic Transmission
Spinal Cord
Diabetic Neuropathies
Virus Diseases
Pain
Wounds and Injuries
Central Nervous System Sensitization
Posterior Horn Cells
Brain-Derived Neurotrophic Factor
Nerve Growth Factors
Acute Pain
p38 Mitogen-Activated Protein Kinases
Interleukin-1
Amputation

Keywords

  • Central sensitization
  • Neuronal-glial interactions
  • p38 mitogen-activated protein kinase
  • Proinflammatory cytokines
  • Spinal cord

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Microglia : A promising target for treating neuropathic and postoperative pain, and morphine tolerance. / Wen, Yeong-Ray; Tan, Ping Heng; Cheng, Jen Kun; Liu, Yen Chin; Ji, Ru Rong.

In: Journal of the Formosan Medical Association, Vol. 110, No. 8, 08.2011, p. 487-494.

Research output: Contribution to journalReview article

Wen, Yeong-Ray ; Tan, Ping Heng ; Cheng, Jen Kun ; Liu, Yen Chin ; Ji, Ru Rong. / Microglia : A promising target for treating neuropathic and postoperative pain, and morphine tolerance. In: Journal of the Formosan Medical Association. 2011 ; Vol. 110, No. 8. pp. 487-494.
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