Upregulation

Upregulation refers to an increase in the number or sensitivity of cellular receptors in response to repeated stimulation or chronic conditions.

In the context of pain, NMDA receptor upregulation in the spinal cord is one of the key mechanisms behind central sensitization, where normal stimuli become excessively painful. Similarly, upregulation of inflammatory mediators and ion channels can heighten nerve excitability.

Understanding upregulation helps explain why chronic pain persists even after healing, and why patients may respond differently to treatments. Therapies that stabilize receptor activity or interrupt abnormal signaling — from pharmacological agents to neuromodulation — aim to counteract this maladaptive process.