Age-dependent sensitization of cutaneous nociceptors during developmental inflammation

Molecular Pain

Renita C Hudgins²  Aaron T Shank²  Frank B Lee²  Jonathon D Weber²  Jessica L Ross²  Michael P Jankowski¹ 

[1] Department of Pediatrics, University of Cincinnati, Cincinnati, OH 45229, USA;Department of Anesthesia, Division of Pain Management, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave MLC 6016, Cincinnati, OH 45229, USA

关键词: Plasticity;    Molecular biology;    Electrophysiology;    Primary afferents;    Inflammation;    Neonate;   

Others  :  861480
DOI  :  10.1186/1744-8069-10-34

 received in 2014-03-28, accepted in 2014-05-22,  发布年份 2014

【 摘 要 】

Background

It is well-documented that neonates can experience pain after injury. However, the contribution of individual populations of sensory neurons to neonatal pain is not clearly understood. Here we characterized the functional response properties and neurochemical phenotypes of single primary afferents after injection of carrageenan into the hairy hindpaw skin using a neonatal ex vivo recording preparation.

Results

During normal development, we found that individual afferent response properties are generally unaltered. However, at the time period in which some sensory neurons switch their neurotrophic factor responsiveness, we observe a functional switch in slowly conducting, broad spiking fibers (“C”-fiber nociceptors) from mechanically sensitive and thermally insensitive (CM) to polymodal (CPM). Cutaneous inflammation induced prior to this switch (postnatal day 7) specifically altered mechanical and heat responsiveness, and heat thresholds in fast conducting, broad spiking (“A”-fiber) afferents. Furthermore, hairy skin inflammation at P7 transiently delayed the functional shift from CM to CPM. Conversely, induction of cutaneous inflammation after the functional switch (at P14) caused an increase in mechanical and thermal responsiveness exclusively in the CM and CPM neurons. Immunocytochemical analysis showed that inflammation at either time point induced TRPV1 expression in normally non-TRPV1 expressing CPMs. Realtime PCR and western blotting analyses revealed that specific receptors/channels involved in sensory transduction were differentially altered in the DRGs depending on whether inflammation was induced prior to or after the functional changes in afferent prevalence.

Conclusion

These data suggest that the mechanisms of neonatal pain development may be generated by different afferent subtypes and receptors/channels in an age-related manner.

【 授权许可】

   
2014 Jankowski et al.; licensee BioMed Central Ltd.

【 图 表 】

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