阿霉素治疗机制研究与进一步思考课件.ppt

* 脊髓层面的疼痛处理，主要显示存在下行抑制通路，一带而过即可。 PURPOSE OF THE SLIDE To discuss the different cell types within the central nervous system, specifically the dorsal horn of the spinal cord, that help to process pain. ? KEY POINTS Peripheral nociceptors synapse with dorsal horn neurons (second-order projection neurons) within the spinal cord.1 There are several types of neurons that synapse in the dorsal horn of the spinal cord; they include: peripheral afferent Aβ-, Aδ- and C-fiber neurons, descending neurons from the brain, γ-aminobutyric acid-ergic interneurons, and glial cells.1 The activity of these neurons may affect the output of the dorsal horn neurons1,2 Excitatory activity from nociceptive and non-nociceptive neurons is transmitted to the dorsal horn neurons. It has been shown that A?-fibers inhibit the firing of dorsal horn neurons in lamina V by activating inhibitory interneurons in lamina II. Conversely, nociceptive neurons (C-, Aδ-fibers) have been shown to inhibit inhibitory neurons.3 Recent evidence suggests that spinal microglial cells actively participate in the pain response. The traditional view of glial cells posited that they were primarily support cells for neurons and were quiescent during a neuronal response. However, glial cells have receptors that are able to respond to neuronal activity. Glial cells also have a number of molecular mediators that are neuroactive (pro-inflammatory cytokines and growth factors). Several hours following nerve injury, markers such as CD11b, TLR4, and CD14 may be released from microglia. Microglial receptors are also overexpressed following nerve injury (e.g., chemokine receptor CX3CR1, and adenosine triphosphate [ATP] receptor P2X4). Blocking or deleting these receptors has been shown to decrease neuropathic pain. Similarly, intrathecal injection of ATP-activated microglia induces mechanical allodynia (nociceptive response to a normally innocuous mechanical stimulation). These data suggest that microglia are involved in media