Peripheral sensitization
The above inflammatory environment, along with other stresses such as hyperosmolarity,61 can affect the function of nociceptors with alterations in ion channel activity (increased sodium and calcium currents at the nociceptor terminal) through changes in gene expression and transcription, as reviewed by Pergolizzi et al28 and Costigan et al.62 The resultant phenotypic change of reduced activation thresholds and increased excitability is termed peripheral sensitization