title: Vagal damage enhances polyneuropathy pain: additive effect of two algogenic mechanisms.
abstract: While the major pain generation in polyneuropathy is in the somatic peripheral nerves, pathologies at visceral nerves might be involved as well. Decreased vagal afferent activity is known to disinhibit pain perception, and therefore might contribute to pain in polyneuropathy. In this study we explored this potential contribution by employing a rat model of vincristine (VCR)-induced pain after sub-diaphragmatic vagotomy (SDV). Forty rats were divided into 4 groups: VCR, SDV, VCR+SDV and controls. Each rat underwent a variety of pain-related behavioral tests including assessment of spontaneous pain, allodynia and hyperalgesia to thermal and mechanical stimuli. We found that VCR+SDV rats had enhanced painful neuropathy compared to VCR alone, expressed as: (1) earlier development of central sensitization: at the first week in rats that underwent SDV+VCR (p<0.0001) and only at the second week in rats injected with VCR alone (p<0.0001), (2) increased incidence of spontaneous pain behavior (p=0.0036), (3) spreading of the spontaneous pain behavior to the forelimbs, (4) higher mechanical dynamic allodynia (tendency, p=0.08) and (5) augmentation of the response to repetitive painful and non-painful mechanical stimuli (p<0.001). Thus, decreased vagal activity aggravates both the severity and the time course of painful polyneuropathy. Therefore, the two mechanisms add to each other in generating the pain picture.
authors.affiliation: Faculty of Social Welfare and Health Sciences, University of Haifa, Israel Department of Neurology, Rambam Medical Center, Haifa, Israel Laboratory of Clinical Neurophysiology, Technion Faculty of Medicine, Haifa, Israel.
authors.forename: Irit
authors.initials: I
authors.lastname: Weissman-Fogel
authors.forename: Arkadi
authors.initials: A
authors.lastname: Dashkovsky
authors.forename: Zeev
authors.initials: Z
authors.lastname: Rogowski
authors.forename: David
authors.initials: D
authors.lastname: Yarnitsky
mesh_terms: D000818:Animals; D006930:Hyperalgesia / Q000503:physiopathology*; D008297:Male; D008959:Models, Neurological; D009473:Neuronal Plasticity; D010147:Pain Measurement; D011115:Polyneuropathies / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014630:Vagus Nerve / Q000503:physiopathology*; D061223:Vagus Nerve Injuries