Pain is an output of the brain and a complex subjective experience. In this chapter, we describe the neuroanatomy and neural mechanisms underlying nociception and pain perception, from the transduction mechanisms in nociceptors through the description of the neural pathways conveying nociceptive information to the brain and its modulation at various neural levels to post-injury sensitization mechanisms. The chapter emphasizes the significance of understanding the neurophysiology and the different types of pain to tailor interventions for individuals dealing with pain. The importance of a comprehensive approach to pain evaluation, going beyond intensity, is underscored with six core outcome domains. These domains, including emotional functioning and global improvement perception, are important in evaluating clinical outcomes for patients with chronic pain. The chapter also guides the reader through the management of chronic pain, describing non-pharmacological and non-invasive interventions. Finally, two adjunct therapies, transcutaneous electrical nerve stimulation and non-invasive brain stimulation, are presented as means to target neural plasticity for enhanced pain management. With strong neurophysiological mechanistic examples and references, this chapter provides students of neuroscience and neurorehabilitation with a comprehensive understanding of pain, guiding them toward nuanced strategies in assessing and rehabilitating individuals living with pain.