Pain originating from spinal nerve roots demonstrates multiple pathogeneses. Distinctions in the patho-anatomy, biomechanics, and pathophysiology of spinal nerve roots contribute to pathology, diagnosis, and management of root-related pain. Root-related pain can emerge from the tension events in the dura mater and nerve tissue associated with primary disc related disorders. Conversely, secondary disc-related degeneration can produce compression on the nerve roots. This compression can result in chemical and mechanical consequences imposed on the nervous tissue within the spinal canal, lateral recess, intervertebral foramina, and extraforminal regions. Differences in root-related pathology can be observed between lumbar, thoracic, and cervical spinal levels, meriting the implementation of different diagnostic tools and management strategies.