Question

Early Approaches

• Acute injury treated through rest, surgery, or medication

• Assumed pain would resolve once tissue healed

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Rise of Pharmacological Management

• Opioids became central due to strong short-term analgesia

• μ-opioid receptor activation suppresses nociceptive transmission

• Long-term use alters reward circuitry, leading to tolerance and dependence

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Shift Toward Non-Invasive Neuromodulation

• Brain stimulation introduced to reduce risk

• Safer than drugs and surgery

• Effectiveness varies widely between individuals

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Key Historical Insight

Pain is not sustained by one region — it is maintained by distributed brain networks and altered metabolism.