title: High spontaneous activity of C-nociceptors in painful polyneuropathy.
abstract: Polyneuropathy can be linked to chronic pain but also to reduced pain sensitivity. We investigated peripheral C-nociceptors in painful and painless polyneuropathy patients to identify pain-specific changes. Eleven polyneuropathy patients with persistent spontaneous pain and 8 polyneuropathy patients without spontaneous pain were investigated by routine clinical methods. For a specific examination of nociceptor function, action potentials from single C-fibres including 214 C-nociceptors were recorded by microneurography. Patients with and without pain were distinguished by the occurrence of spontaneous activity and mechanical sensitization in C-nociceptors. The mean percentage of C-nociceptors being spontaneously active or mechanically sensitized was significantly higher in patients with pain (mean 40.5% and 14.6%, respectively, P=.02). The difference was mainly due to more spontaneously active mechanoinsensitive C-nociceptors (operationally defined by their mechanical insensitivity and their axonal characteristics) in the pain patients (19 of 56 vs 6 of 43; P=.02). The percentage of sensitized mechanoinsensitive C-nociceptors correlated to the percentage of spontaneously active mechanoinsensitive C-nociceptors (Kendall's tau=.55, P=.004). Moreover, spontaneous activity of mechanoinsensitive C-nociceptors correlated to less pronounced activity-dependent slowing of conduction (Kendall's tau=-.48, P=.009), suggesting that axons were included in the sensitization process. Hyperexcitability in mechanoinsensitive C-nociceptors was significantly higher in patients with polyneuropathy and pain compared to patients with polyneuropathy without pain, while the difference was much less prominent in mechanosensitive (polymodal) C-nociceptors. This hyperexcitability may be a major underlying mechanism for the pain experienced by patients with painful peripheral neuropathy.
authors.affiliation: Section of Clinical Neurophysiology, Department of Neurology, Oslo University Hospital, Rikshospitalet, Oslo, Norway Department of Physiology and Experimental Pathophysiology, University of Erlangen/Nürnberg, Erlangen, Germany Department of Clinical Neurophysiology, University Hospital, Uppsala, Sweden Department of Anesthesiology and Operative Intensive Care, Mannheim, Heidelberg University, Germany.
authors.forename: Inge Petter
authors.initials: IP
authors.lastname: Kleggetveit
authors.forename: Barbara
authors.initials: B
authors.lastname: Namer
authors.forename: Roland
authors.initials: R
authors.lastname: Schmidt
authors.forename: Tormod
authors.initials: T
authors.lastname: Helås
authors.forename: Michael
authors.initials: M
authors.lastname: Rückel
authors.forename: Kristin
authors.initials: K
authors.lastname: Ørstavik
authors.forename: Martin
authors.initials: M
authors.lastname: Schmelz
authors.forename: Ellen
authors.initials: E
authors.lastname: Jørum
mesh_terms: D000200:Action Potentials; D000328:Adult; D000368:Aged; D001683:Biological Clocks; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009437:Neuralgia / Q000150:complications* / Q000503:physiopathology*; D009619:Nociceptors; D011115:Polyneuropathies / Q000150:complications* / Q000503:physiopathology*