Neuropathic Pain: Mechanisms, Clinical Features, and Diagnostic Patterns
Neuropathic pain is a complex pain condition that arises from injury or dysfunction of the peripheral or central nervous system. Unlike nociceptive pain, which is proportional to tissue injury, neuropathic pain is often described by patients as severe, disproportionate, spontaneous, continuous, or lingering, even in the absence of an ongoing stimulus. It may persist long after tissue healing has occurred and frequently presents significant diagnostic and therapeutic challenges.
In clinical practice, neuropathic pain is identified by characteristic stimulus-induced and spontaneous pain phenomena, which reflect abnormal neural processing at the peripheral and/or central level.
Key Characteristics of Neuropathic Pain
Patients with neuropathic pain often report sensations such as burning, electric shock–like pain, stabbing discomfort, or persistent aching. The pain may be triggered by normally non-painful stimuli or occur without any apparent external provocation. These features indicate altered sensory signal processing, including peripheral sensitization, central sensitization, or both.
Stimulus-Induced Neuropathic Pain Phenomena
Several hallmark sensory abnormalities are used to identify and classify neuropathic pain.
Allodynia
Allodynia is defined as a painful response to a stimulus that is normally non-painful. A classic example is severe pain elicited by lightly brushing the skin over an injured area, while the same stimulus applied to adjacent normal skin is painless.
Allodynia occurs when axons of cutaneous afferent neurons become sensitized to mechanical stimulation. Local inflammatory mediators at or near injured nerve terminals—such as bradykinin, prostaglandins, and other endogenous substances—lower the activation threshold of sensory neurons. This sensitization increases both responsiveness and firing frequency in response to normally innocuous stimuli, leading to exaggerated pain perception.
Anesthesia Dolorosa
Anesthesia dolorosa describes a paradoxical condition in which pain is perceived in an area that is otherwise completely anesthetic. Patients report persistent pain despite the absence of tactile, thermal, or nociceptive sensation in the affected region.
Importantly, this pain does not resolve with peripheral nerve blocks, indicating a central origin of the pain signal. Anesthesia dolorosa is most often associated with deafferentation injuries and represents maladaptive central nervous system reorganization rather than ongoing peripheral pathology.
Hyperalgesia
Hyperalgesia refers to an enhanced pain response to a normally painful stimulus. In this condition, pain thresholds are abnormally lowered. For example, the normal thermal pain tolerance over the mental fold in a healthy adult ranges between 48°C and 50°C. If pain is elicited at 45°C, hyperalgesia is present.
Patients with hyperalgesia still perceive pain appropriately, but the intensity of pain is exaggerated, and stimuli that were previously tolerable become painful. This phenomenon reflects increased excitability of nociceptive pathways at the peripheral or central level.
Hyperpathia
Hyperpathia is a neuropathic pain syndrome characterized by an abnormally painful response to repetitive stimulation, combined with an increased threshold for pain perception. It is distinguished by delayed onset of pain, prolonged aftersensation, and exaggerated responses once pain is triggered.
During neurosensory testing, hyperpathia may be identified by applying repeated tactile stimuli, such as Semmes-Weinstein monofilaments, at a rate of approximately one stimulus per second. Pain may begin only after several stimuli, demonstrating temporal summation, and may persist for more than one minute after stimulation ends, known as aftersensation. If pain intensity increases with continued stimulation, overshoot is present.
The presence of delayed onset, aftersensation, overshoot, or summation—alone or in combination—is sufficient to diagnose a hyperpathic pain condition.
Sympathetic Maintained Pain (SMP)
Sympathetic maintained pain is a subtype of neuropathic pain in which pain is sustained by abnormal interactions between the sympathetic and sensory nervous systems. In this condition, sympathetic efferent activity induces tonic firing in sensitized wide-dynamic range (WDR) or multireceptive neurons within central nociceptive pathways.
This sustained neural activity results in a burning pain sensation. Importantly, regional nerve blocks may reduce mechanical sensitivity but do not eliminate the tonic firing of central neurons, distinguishing SMP from purely peripheral neuropathic pain.
Brush-stroke directional testing may demonstrate mechanical allodynia in SMP, but this test alone cannot differentiate sympathetic maintained pain from other forms of mechanical allodynia, highlighting the importance of comprehensive clinical assessment.
Clinical Significance
Neuropathic pain conditions are commonly encountered following nerve injury, dental trauma, oral and maxillofacial surgery, facial fractures, or chronic compression syndromes. Accurate identification of neuropathic pain patterns is essential, as treatment strategies differ significantly from those used for nociceptive pain.
Early recognition and proper classification improve diagnostic accuracy, guide appropriate referral, and prevent unnecessary interventions.
Conclusion
Neuropathic pain represents a maladaptive response of the nervous system characterized by abnormal sensory processing. Conditions such as allodynia, anesthesia dolorosa, hyperalgesia, hyperpathia, and sympathetic maintained pain reflect distinct mechanisms involving peripheral sensitization, central sensitization, and autonomic involvement. Understanding these patterns allows clinicians to accurately diagnose neuropathic pain and tailor management strategies accordingly.
