Capsaicin-evoked mechanical allodynia and hyperalgesia cross nerve territories. Evidence for a central mechanism

Abstract

Background: The finding in some patients with neuropathic pain that mechanical allodynia (pain evoked by light touch) and hyperalgesia (supranormal pain evoked by painful stimuli) extend beyond the territory of a single nerve or spinal sensory root (extraterritorial pain) often prompts a diagnosis of psychiatric illness. The hypothesis that focal nociceptive input in a single nerve territory can result in allodynia and hyperalgesia in a nerve territory adjacent to the input was investigated in normal human subjects.

Methods: On separate days, 13 healthy volunteers each received left radial and ulnar nerve blocks. After block of either nerve, sensation remaining for three classes of afferents (A beta low-threshold mechanoreceptors, A delta nociceptors, and C polymodal nociceptors) allowed inference of the nerve territory of the adjacent nerve, and the area of overlapping innervation. On a third day, 1,000 micrograms intradermal capsaicin was administered into a site such that C-nociceptor input was confined to the ulnar nerve territory. Areas of brush allodynia and pinprick hyperalgesia were determined.

Results: Spread of brush allodynia beyond all three borders of the ulnar nerve territory occurred in 9 of 13 patients (for these subjects, range 5-28 mm), whereas spread of pinprick hyperalgesia beyond all borders of the ulnar nerve territory occurred in 12 of 13 subjects (range 1-31 mm). Spread of brush allodynia beyond the A beta border of the ulnar nerve territory occurred in 10 of 13 subjects (range 4-35 mm); and spread of pinprick hyperalgesia beyond the A delta border of the ulnar nerve territory occurred in 12 of 13 subjects (range 1-31 mm).

Conclusions: It is concluded that activation of C-nociceptors evokes a state of central sensitization that may manifest itself by the appearance of extraterritorial pain abnormalities.