Wind-up phenomenon

The wind-up phenomenon refers to the progressive increase in pain intensity when repeated stimuli of the same strength are applied to nociceptors.

It is caused by enhanced activity of NMDA receptors in the spinal cord, leading to increased excitability of pain pathways. Clinically, this explains why repeated or persistent stimulation can make pain feel more intense over time, even if the actual input doesn’t change.
Wind-up is a central feature of central sensitization, contributing to conditions such as fibromyalgia, neuropathic pain and chronic low back pain. Therapies that block NMDA receptors (such as ketamine) or reduce spinal cord excitability can help counteract wind-up, making it an important concept in both research and treatment planning.