Hyperexcitable polymodal and insensitive nociceptors in painful human neuropathy.
Six patients with chronic pain, mechanical and thermal hyperalgesia/allodynia, and cutaneous vasodilatation starting distally in their extremities, were evaluated using clinical and neurophysiological methods and microneurography. Evidence of small-fiber polyneuropathy was documented in all, but the etiology remained cryptogenic in several. Different forms of hyperexcitability were detected by microneurography in both common polymodal and mechanically insensitive C nociceptors, which explain all the somatosensory abnormalities. Signs of hyperexcitability included reduced receptor threshold (accounting for mechanical and heat allodynias), spontaneous C nociceptor discharge (explaining spontaneous "burning" pain and antidromic vasodilatation), and multiplied nociceptor responses to stimulation (accounting for hyperalgesia). The clinical and electrophysiological profiles of these patients resemble the experimental syndrome evoked by application of capsaicin to the skin. This similarity, and the striking heat dependence of the spontaneous pain, suggest that a common feature may be altered expression or modulation of vanilloid 1 receptor, provoking abnormal nociceptor discharges.
Ochoa
José L
JL
Good Samaritan Hospital & Medical Center Oregon Health & Science University, Portland, Oregon 97210, USA. jochoa@nervesense.net
Campero
Mario
M
Serra
Jordi
J
Bostock
Hugh
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003937:Diagnosis, Differential; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D008839:Microelectrodes; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000294:innervation / Q000503:physiopathology; D009422:Nervous System Diseases / Q000175:diagnosis / Q000503:physiopathology*; D009619:Nociceptors / Q000503:physiopathology*; D010147:Pain Measurement; D010525:Peripheral Nerves / Q000503:physiopathology; D012677:Sensation / Q000502:physiology; D012678:Sensation Disorders / Q000175:diagnosis / Q000503:physiopathology*; D012684:Sensory Thresholds / Q000502:physiology; D012720:Severity of Illness Index; D013817:Thermography