Genetic deletion of microglial Panx1 attenuates morphine withdrawal, but not analgesic tolerance or hyperalgesia in mice

Channels (Austin). 2017 Sep 3;11(5):487-494. doi: 10.1080/19336950.2017.1359361. Epub 2017 Jul 26.


Opioids are among the most powerful analgesics for managing pain, yet their repeated use can lead to the development of severe adverse effects. In a recent study, we identified the microglial pannexin-1 channel (Panx1) as a critical substrate for opioid withdrawal. Here, we investigated whether microglial Panx1 contributes to opioid-induced hyperalgesia (OIH) and opioid analgesic tolerance using mice with a tamoxifen-inducible deletion of microglial Panx1. We determined that escalating doses of morphine resulted in thermal pain hypersensitivity in both Panx1-expressing and microglial Panx1-deficient mice. In microglial Panx1-deficient mice, we also found that acute morphine antinociception remained intact, and repeated morphine treatment at a constant dose resulted in a progressive decline in morphine antinociception and a reduction in morphine potency. This reduction in morphine antinociceptive potency was indistinguishable from that observed in Panx1-expressing mice. Notably, morphine tolerant animals displayed increased spinal microglial reactivity, but no change of microglial Panx1 expression. Collectively, our findings indicate microglial Panx1 differentially contributes to opioid withdrawal, but not the development of opioid-induced hyperalgesia or tolerance.

Keywords: microglia; opioid analgesic tolerance; opioid withdrawal; opioid-induced hyperalgesia; pannexin-1.

MeSH terms

  • Animals
  • Connexins / genetics*
  • Dose-Response Relationship, Drug
  • Drug Tolerance
  • Humans
  • Hyperalgesia / metabolism*
  • Hyperalgesia / physiopathology
  • Male
  • Mice
  • Microglia / metabolism*
  • Morphine / pharmacology*
  • Narcotics / pharmacology*
  • Nerve Tissue Proteins / genetics*
  • Pain / metabolism
  • Pain / physiopathology
  • Substance Withdrawal Syndrome / metabolism
  • Substance Withdrawal Syndrome / physiopathology


  • Connexins
  • Narcotics
  • Nerve Tissue Proteins
  • Panx1 protein, mouse
  • Morphine