神经生物学系知识库

Long term opioid treatment results in hyperalgesia and tolerance, which is a troublesome phenomenon in clinic application. Recent studies have revealed a critical role of toll-like receptor 4 (TLR4) in the neuropathological process of opioid-induced hyperalgesia and tolerance. TLR4 is predominantly expressed by microglial cells and is a key modulator in the activation of the innate immune system. Activation of TLR4 may initiate the activation of microglia and hence a number of neurotransmitters and neuromodulators that could enhance neuronal excitability are released. Blockade of TLR4 activation by its antagonists alleviate neuropathic pain. We hypothesized that opioid antagonists such as naloxone and naltrexone, which were also demonstrated to be TLR4 antagonist, may have clinic application value in attenuation of opioid-induced hyperalgesia and tolerance. (C) 2012 Elsevier Ltd. All rights reserved.