Background  The discovery that glial activation plays a critical role in the modulation of neuronal functions and affects the spinal processing of nociceptive signalling has brought new understanding on the mechanisms underlying central sensitization involved in chronic pain facilitation. Spinal glial activation is now considered an important component in the development and maintenance of allodynia and hyperalgesia in various models of chronic pain, including neuropathic pain and pain associated with peripheral inflammation. In addition, spinal glial activation is also involved in some forms of visceral hyperalgesia.

Purpose  We discuss the signalling pathways engaged in central glial activation, including stress pathways, and the neuron–glia bidirectional relationships involved in the modulation of synaptic activity and pain facilitation. In this expanding field of research, the characterization of the mechanisms by which glia affect spinal neuro‐transmission will increase our understanding of central pain facilitation, and has the potential for the development of new therapeutic agents for common chronic pain conditions.