A remarkable series of findings over the last decade or so has demonstrated a previously unrecognized role for CNS glia in many aspects of neuronal functioning including pain processing. In addition to their recruitment to sites of CNS damage, these cells also appear to be capable of "action at a distance," playing functional roles in areas of CNS that are quite remote from the focus of injury or disease. The implication is that the nervous system is able to initiate signals that alter the function of these glial cells, and these cells in turn release factors that regulate neuronal function. This idea has taken root, resulting in an explosion of research interest, and here we look critically at what has been reported in order to assess where knowledge is missing or uncertain.
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