Most Common Causes of Hyperesthesia
The most common causes of hyperesthesia are peripheral neuropathies (particularly diabetic neuropathy), opioid-induced hyperalgesia (especially with high-dose remifentanil), and central sensitization from nerve injury or chronic pain conditions. 1, 2, 3
Primary Etiological Categories
Peripheral Neuropathy-Related Hyperesthesia
Diabetic neuropathy is the single most common cause of hyperesthesia in clinical practice, presenting with burning sensations and troublesome hyperesthesia in a stocking-and-glove distribution. 3 This occurs through two distinct mechanisms:
- Acute diabetic sensory neuropathy causes severe hyperesthetic symptoms with minimal neurological signs, typically improving within one year. 3
- Chronic sensorimotor neuropathy produces persistent hyperesthesia for years, accompanied by patchy sensory loss and peripheral muscle wasting. 3
- Blood glucose flux and altered peripheral blood flow increase spontaneous activity in nociceptive afferent fibers within axonal sprouts characteristic of small fiber neuropathy. 3
Other neuropathic causes include toxic exposures, vitamin deficiencies (B12, B6, folates), thyroid dysfunction, and chemotherapy agents (bortezomib, thalidomide, taxanes). 4
Opioid-Induced Hyperalgesia (OIH)
High intraoperative doses of remifentanil consistently produce hyperalgesia, manifesting as higher postoperative pain intensity and increased morphine requirements compared to lower doses. 1 This mechanism operates through:
- Long-term potentiation at C-fiber synapses in the spinal dorsal horn. 1
- Reduced mechanical pain threshold near surgical wounds. 1
- Increased pain sensation to external hot and cold stimuli, influenced by the rate of remifentanil withdrawal. 1
OIH can present as: diffuse pain spreading to other locations, increased pain intensity over time during ongoing opioid administration, or increased pain sensation to external stimuli such as touch. 1
Central Sensitization Mechanisms
Nerve injury and chronic pain conditions produce hyperesthesia through central nervous system changes:
- Pathologically active or sensitized nociceptors induce spinal cord hyperexcitability, causing light touch (Aβ-fiber input) to be perceived as pain. 5
- Patients characteristically have spontaneous pain, heat hyperalgesia, static mechanical allodynia, and severe dynamic mechanical allodynia. 5
- Anatomic reorganization in the dorsal horn from C-fiber degeneration leads to Aβ-fiber-mediated allodynia. 5
Inflammatory and Sympathetically Maintained Pain
Persistent inflammatory reactions of nerve trunks induce ectopic activity in primary afferent nociceptors through tumor necrosis factor-alpha produced by activated macrophages. 5 After nerve lesions, sympathetic nervous system activity can enhance pain and allodynia via noradrenaline released from sympathetic terminals acting on newly expressed receptors. 5
Clinical Presentation Patterns
Two Distinct Phenotypes
Research demonstrates that patients with painful dysesthesia present as two separate groups: 6
- Neurogenic hyperalgesia group: Lowered pain thresholds (by approximately -1.94 log2 units) with minor sensory impairment, caused by central sensitization. 6
- Painful hypoalgesia group: Elevated pain thresholds (by approximately 3.02 log2 units) with major sensory deficit, caused by partial nociceptive deafferentation. 6
Diabetic-Specific Patterns
In diabetic polyneuropathy, heat stimulus-induced hyperesthesia (low thresholds) occurs especially in mild disease and correlates with symptoms and impairments, indicating true hyperalgesia rather than supersensitivity. 7 Steeper pain-stimulus response slopes are significantly associated with sensory symptoms, including pain severity. 7
Critical Diagnostic Considerations
Cervical spinal cord pathology can present with bilateral hand numbness and burning dysesthesias, requiring urgent imaging if suspected. 8 Small sensory nerve injury during surgical procedures can produce localized hyperesthesia, though this is less common than anesthesia. 2
Important caveat: Multiple mechanisms can operate simultaneously in a single disease entity (such as postherpetic neuralgia) and in individual patients, with pain-generating mechanisms potentially changing during disease progression. 5