Plasticity of calcitonin gene related peptide neurotransmission in the spinal cord during peripheral inflammation.
Injection of complete Freund's adjuvant (CFA; 75 microL) into the plantar surface of the hind paw of the rat results in a mild inflammation that lasts for several days and is accompanied by hyperalgesia. Multiple components of calcitonin gene related peptide (CGRP) neurotransmission in the spinal cord are altered during the course of this peripheral inflammation. The content of immunoreactive (i) CGRP in the dorsal horn of the spinal cord, where primary afferent neurons terminate, is significantly decreased within 2 days after injection of CFA but increases to a level greater than that of the control at 8 days. The early decrease in iCGRP in the spinal cord suggests that the release of CGRP from primary afferent neurons is increased during the period of maximal hyperalgesia that accompanies peripheral inflammation. Changes in the mRNA for CGRP suggest that the increase in spinal content of iCGRP is due to an increase in synthesis of the peptide as the level of mRNA for CGRP is increased from 2 to 8 days after injection of CFA. Despite the decrease in the content of iCGRP in the spinal cord, there is no apparent decrease in the amount of iCGRP that can be released from the dorsal spinal cord by capsaicin; in fact, capsaicin-evoked release is increased at 4 days. Measurements of the binding of 125I-labelled CGRP in the dorsal spinal cord indicate that high affinity binding sites for CGRP are downregulated at 4 days after injection of CFA. In total, these data support the hypothesis that the activity of CGRP-containing primary afferent neurons is increased during peripheral inflammation. CGRP released from primary afferent neurons in the spinal cord may contribute to cellular changes that accompany peripheral inflammation.
Seybold
V S
VS
Department of Cell Biology and Neuroanatomy, University of Minnesota, School of Medicine, Minneapolis 55455, USA.
Galeazza
M T
MT
Garry
M G
MG
Hargreaves
K M
KM
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D009473:Neuronal Plasticity; D013116:Spinal Cord / Q000378:metabolism*; D009435:Synaptic Transmission
D015740:Calcitonin Gene-Related Peptide