Mechanism of Referred Pain
Referred pain occurs primarily through central sensitization of convergent neurons in the dorsal horn of the spinal cord, where sensory inputs from different body regions synapse onto the same second-order neurons, causing the brain to mislocalize the pain source. 1, 2
Primary Mechanism: Convergence-Projection Theory
The convergence-projection theory remains the central explanation for referred pain, where a single dorsal horn neuron receives convergent input from two different body regions—typically from both visceral organs and somatic structures. 1, 2
Key pathophysiological steps:
- Nociceptive signals from an affected organ (such as the heart or gallbladder) activate dorsal horn neurons that also receive input from somatic structures 1
- Because thalamic neurons cannot distinguish which peripheral source activated the dorsal horn neuron, the brain misinterprets the pain location 2
- This explains why cardiac ischemia produces pain radiating to the left arm, neck, and jaw—these somatic areas share spinal cord segments with cardiac afferents 3
- Similarly, gallbladder disease causes right shoulder pain through shared innervation at the C3-C5 spinal levels 3
Secondary Mechanism: Peripheral Reflexes and Neuroplastic Changes
Beyond simple convergence, acute changes in dorsal horn synaptic connections contribute to referred pain patterns. 2
- Dorsal horn neurons possess normally ineffective synaptic connections that become functional under nociceptive input 2
- The neuropeptide substance P facilitates these synaptic changes during muscle pain and its referral 2
- Dichotomizing afferent fibers (single neurons with branches to multiple tissues) may create peripheral reflexes that contribute to pain referral 1
Clinical Examples
Myocardial infarction: Cardiac pain radiates to the left and/or right arm, neck, and back because cardiac afferents converge with somatic afferents from these regions in the upper thoracic spinal cord segments. 3 Women more frequently experience referred pain in the back, neck, and jaw compared to men. 3
Gallbladder disease: Biliary pain occurs from increased gallbladder pressure and can refer to the right shoulder and scapular region through shared C3-C5 innervation. 3 The pain builds to a steady level, lasts at least 30 minutes, and is severe enough to interrupt activities. 3
Central Sensitization and Chronic Pain
Central sensitization amplifies referred pain patterns over time. 3, 1
- Chronic ischemia or tissue injury leads to heightened dorsal horn neuron excitability 3
- This creates expanded receptive fields where stimulation of previously non-painful areas now triggers pain 4
- Even after tissue healing, central mechanisms may remain sensitized and produce exaggerated responses when re-challenged 4
- The gate control theory explains how emotional factors (depression, anxiety) and behavioral factors can modulate these ascending pain signals through descending cortical pathways 3
Important Clinical Pitfalls
Do not assume referred pain patterns are always consistent. Individual variation exists in spinal cord convergence patterns, and pain referral areas can be more expansive in individuals with prior musculoskeletal trauma even after complete recovery. 4
Recognize that referred pain is fundamentally different from radicular pain. Referred pain results from convergent dorsal horn neurons, while radicular pain follows specific dermatomal distributions from nerve root compression. 1 This distinction is critical for diagnosis and treatment planning.
Women may describe cardiac referred pain differently than men, using descriptors like "tearing" more frequently and experiencing pain more often in atypical locations (back, neck, jaw). 3 This can lead to delayed recognition of cardiac ischemia if clinicians expect "classic" male presentation patterns.