Expression of platelet–derived growth factor receptors in primary afferents and their effect on pain behaviors

Platelet–derived growth factor receptors (PDGFRs; PDGFRα and PDGFRβ) play an important role in wound–healing after tissue injury. They are expressed in the peripheral tissues and nervous system. However, their role within the peripheral nervous system is not fully understood. In this study, we investigated the expression of PDGFRs in primary afferents and its role in pain perception in rats. In situ hybridization histochemistry (ISHH) revealed that PDGFRα mRNA was expressed in approximately 15% of small–, medium–, and large–sized dorsal root ganglion (DRG) neurons. PDGFRβ mRNAs were expressed in approximately 30% of small–sized DRG neurons, suggesting that PDGFRβ was localized in a subpopulation of nociceptors. Double labeling analysis of ISHH with immunohistochemistry showed that PDGFRβ mRNAs were relatively colocalized with P2X3–positive neurons. In behavioral tests, intraplantar injection of both PDGF–AA and PDGF–BB, ligands for PDGFRα and PDGFRβ, respectively, did not alter withdrawal threshold or latencies to mechanical and thermal stimulation compared to that in vehicle–treated rats and did not evoke spontaneous nocifensive behaviors. Interestingly, PDGF–BB, but not PDGF–AA, increased nocifensive behaviors and c–Fos expression in the superficial dorsal horn induced by αβ–Me–ATP, a P2X3 agonist. Further, pretreatment with PDGF–BB enhanced Ca2+ influx and the number of responsive DRG neurons in response to αβ–Me–ATP. These results suggests that PDGF–BB sensitizes P2X3 receptors via PDGFRβ in primary afferents, leading to nocifensive behaviors.