Immune-to-Brain Communication in Pain: Historical Perspectives, New Directions

Symptoms of neuropathic pain are often severely debilitating, such as spontaneous pain and dysaesthesia, and the exaggerated pain states of allodynia and hyperalgesia. Research of recent years has shown pain is not modality-specific, but rather that pain processing is an integrated matrix that occurs at the peripheral, spinal, and supraspinal sites. This chapter describes neuronal pain-processing matrix. It summarizes the neuronal adaptations that contribute to pathological pain processing. Such an overview of these neuronal systems is vital to understanding where and how the immune system can modulate pain processing. Whilst glial activation could be demonstrated experimentally, the manner in which glia are activated following nerve injury was still unresolved. Apart from activation by the neurotransmitters and neuromodulators released from the presynaptic terminals of nociceptive primary afferents, much of glial activation can be understood from their immunocompetent status.