Neurogenic hyperalgesia versus painful hypoalgesia: two distinct mechanisms of neuropathic pain

&NA; Patients with sensory disturbances of painful and non‐painful character show distinct changes in touch and/or pain sensitivity. The patterns of sensory changes were compared to those of human surrogate models of neuropathic pain to assess the underlying mechanisms. We investigated 30 consecutive in‐patients with dysaesthesia of various origins (peripheral, spinal, and brainstem lesions) and 15 healthy subjects. Tactile thresholds were determined with calibrated von Frey hairs (1.1 mm ∅). Thresholds and stimulus–response functions for pricking pain were determined with a series of calibrated punctate mechanical stimulators (0.2 mm ∅). Allodynia was tested by light stroking with a brush, Q‐tip, and cotton wisp. Perceptual wind‐up was tested by trains of punctate stimuli at 0.2 or 1 Hz. Intradermal injection of capsaicin (n=7) and A‐fiber conduction blockade (n=8) served as human surrogate models for neurogenic hyperalgesia and partial nociceptive deafferentation, respectively. Patients without pain (18/30) showed a continuous distribution of threshold shifts in the dysaesthetic skin area with a low to moderate increase in pain threshold (by 1.52±0.45 log2 units). Patients with painful dysaesthesia presented as two separate groups (six patients each): one showing lowered pain thresholds (by −1.94±0.46 log2 units, hyperalgesia) and the other elevated pain thresholds (by 3.02±0.48 log2 units, hypoalgesia). The human surrogate model of neurogenic hyperalgesia revealed nearly identical leftward shifts in stimulus–response function for pricking pain as patients with spontaneous pain and hyperalgesia (by a factor of about 5 each). The sensory changes in the human surrogate model of deafferentation were similar to patients with hypoalgesia and spontaneous pain (rightward shift of the stimulus–response function with a decrease in slope). Perceptual wind‐up did not differ between symptomatic and control areas. There was no exclusive association of any parameter obtained by quantitative sensory testing with a particular disease (of either peripheral or central origin). Our findings suggest that neuropathic pain is based on two distinct mechanisms: (I) central sensitization (neurogenic hyperalgesia; in patients with minor sensory impairment) and (II) partial nociceptive deafferentation (painful hypoalgesia; in patients with major sensory deficit). This distinction as previously postulated for postherpetic neuralgia, is obviously valid also for other conditions. Our findings emphasize the significance of a mechanism‐based classification of neuropathic pain.