title: Transient cervical nerve root compression modulates pain: load thresholds for allodynia and sustained changes in spinal neuropeptide expression.
abstract: Nerve root compression produces chronic pain and altered spinal neuropeptide expression. This study utilized controlled transient loading in a rat model of painful cervical nerve root compression to investigate the dependence of mechanical allodynia on load magnitude. Injury loads (0-110mN) were applied quasistatically using a customized loading device, and load thresholds to produce maintained mechanical allodynia were defined. Bilateral spinal expression of substance P (SP) and calcitonin gene-related peptide (CGRP) was assessed 7 days following compression using immunohistochemistry to determine relationships between these neuropeptides and compression load. A three-segment change point model was implemented to model allodynia responses and their relationship to load. Load thresholds were defined at which ipsilateral and contralateral allodynia were produced and sustained. The threshold for increased allodynia was lowest for acute (day 1) ipsilateral responses (26.29mN), while thresholds for allodynia on day 7 were similar for the ipsilateral (38.16mN) and contralateral forepaw (38.26mN). CGRP, but not SP, significantly decreased with load; the thresholds for ipsilateral and contralateral CGRP decreases corresponded to 19.52 and 24.03mN, respectively. These thresholds suggest bilateral allodynia may be mediated by spinal mechanisms, and that these mechanisms depend on the magnitude of load.
authors.affiliation: Department of Bioengineering, University of Pennsylvania, 240 Skirkanich Hall, 210 South 33rd Street, Philadelphia, PA 19104-6321, USA.
authors.forename: Raymond D
authors.initials: RD
authors.lastname: Hubbard
authors.forename: Zhen
authors.initials: Z
authors.lastname: Chen
authors.forename: Beth A
authors.initials: BA
authors.lastname: Winkelstein
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis*; D019245:Compressive Strength; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D019547:Neck Pain / Q000378:metabolism* / Q000473:pathology; D009408:Nerve Compression Syndromes / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D013373:Substance P / Q000096:biosynthesis*
chemical_list: D013373:Substance P; D015740:Calcitonin Gene-Related Peptide