Activin induces tactile allodynia and increases calcitonin gene-related peptide after peripheral inflammation.
Calcitonin gene-related peptide (CGRP) is a sensory neuropeptide important in inflammatory pain that conveys pain information centrally and dilates blood vessels peripherally. Previous studies indicate that activin A increases CGRP-immunoreactive (IR) sensory neurons in vitro, and following wound, activin A protein increases in the skin and more neurons have detectable CGRP expression in the innervating dorsal root ganglion (DRG). These data suggest some adult sensory neurons respond to activin A or other target-derived factors with increased neuropeptide expression. This study was undertaken to test whether activin contributes to inflammatory pain and increased CGRP and to learn which neurons retained plasticity. After adjuvant-induced inflammation, activin mRNA, but not NGF or glial cell line-derived neurotrophic factor, increased in the skin. To examine which DRG neurons increased CGRP immunoreactivity, retrograde tracer-labeled cutaneous neurons were characterized after inflammation. The proportion and size of tracer-labeled DRG neurons with detectable CGRP increased after inflammation. One-third of CGRP-IR neurons that appear after inflammation also had isolectin B4 binding, suggesting that some mechanoreceptors became CGRP-IR. In contrast, the increased proportion of CGRP-IR neurons did not appear to come from RT97-IR neurons. To learn whether central projections were altered after inflammation, CGRP immunoreactivity in the protein kinase Cgamma-IR lamina IIi was quantified and found to increase. Injection of activin A protein alone caused robust tactile allodynia and increased CGRP in the DRG. Together, these data support the hypothesis that inflammation and skin changes involving activin A cause some sensory neurons to increase CGRP expression and pain responses.
Xu
Pin
P
Department of Neuroscience, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
Van Slambrouck
Charles
C
Berti-Mattera
Liliana
L
Hall
Alison K
AK
D028341:Activins; D000818:Animals; D000842:Ankle / Q000294:innervation / Q000503:physiopathology; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005620:Freund's Adjuvant; D005727:Ganglia, Spinal / Q000166:cytology; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D006941:Hyperesthesia / Q000139:chemically induced / Q000503:physiopathology; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D028322:Inhibin-beta Subunits; D020932:Nerve Growth Factor / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000378:metabolism*; D012333:RNA, Messenger; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D013997:Time Factors; D014110:Touch
D012333:RNA, Messenger; C422405:activin A; D028341:Activins; D005620:Freund's Adjuvant; D020932:Nerve Growth Factor; D028322:Inhibin-beta Subunits; D015740:Calcitonin Gene-Related Peptide