title: Eccentric muscle contraction and stretching evoke mechanical hyperalgesia and modulate CGRP and P2X(3) expression in a functionally relevant manner.
abstract: Non-invasive, movement-based models were used to investigate muscle pain. In rats, the masseter muscle was rapidly stretched or electrically stimulated during forced lengthening to produce eccentric muscle contractions (EC). Both EC and stretching disrupted scattered myofibers and produced intramuscular plasma extravasation. Pro-inflammatory cytokines (IL-1beta, TNF-alpha, IL-6) and vascular endothelial growth factor (VEGF) were elevated in the masseter 24h following EC. At 48h, neutrophils increased and ED1 macrophages infiltrated myofibers while ED2 macrophages were abundant at 4d. Mechanical hyperalgesia was evident in the ipsilateral head 4h-4d after a single bout of EC and for 7d following multiple bouts (1 bout/d for 4d). Calcitonin gene-related peptide (CGRP) mRNA increased in the trigeminal ganglion 24h following EC while immunoreactive CGRP decreased. By 2d, CGRP-muscle afferent numbers equaled naive numbers implying that CGRP is released following EC and replenished within 2d. EC elevated P2X(3) mRNA and increased P2X(3) muscle afferent neuron number for 12d while electrical stimulation without muscle contraction altered neither CGRP nor P2X(3) mRNA levels. Muscle stretching produced hyperalgesia for 2d whereas contraction alone produced no hyperalgesia. Stretching increased CGRP mRNA at 24h but not CGRP-muscle afferent number at 2-12d. In contrast, stretching significantly increased the number of P2X(3) muscle afferent neurons for 12d. The sustained, elevated P2X(3) expression evoked by EC and stretching may enhance nociceptor responsiveness to ATP released during subsequent myofiber damage. Movement-based actions such as EC and muscle stretching produce unique tissue responses and modulate neuropeptide and nociceptive receptor expression in a manner particularly relevant to repeated muscle damage.
authors.affiliation: Department of Neural and Pain Sciences, University of Maryland, 650 West Baltimore Street, Baltimore, MD 21201, USA Graduate Program in Neuroscience, University of Maryland, Baltimore, MD, USA Department of Obstetrics and Gynecology, University of Texas, Galveston, TX 77555, USA.
authors.forename: Dean
authors.initials: D
authors.lastname: Dessem
authors.forename: Ranjinidevi
authors.initials: R
authors.lastname: Ambalavanar
authors.forename: Melena
authors.initials: M
authors.lastname: Evancho
authors.forename: Aicha
authors.initials: A
authors.lastname: Moutanni
authors.forename: Chandrasekhar
authors.initials: C
authors.lastname: Yallampalli
authors.forename: Guang
authors.initials: G
authors.lastname: Bai
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D009470:Muscle Spindles / Q000502:physiology; D018482:Muscle, Skeletal / Q000293:injuries* / Q000294:innervation / Q000378:metabolism*; D009135:Muscular Diseases / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism*; D058477:Receptors, Purinergic P2X3; D012668:Trigeminal Ganglion / Q000166:cytology / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; D058477:Receptors, Purinergic P2X3; D042461:Vascular Endothelial Growth Factor A; D000255:Adenosine Triphosphate; D015740:Calcitonin Gene-Related Peptide