Chronic inflammatory pain upregulates expression of P2Y2 receptor in small-diameter sensory neurons
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Roles of ionotropic purinergic (P2X) receptors in chronic pain have been intensively investigated. However, the contribution of metabotropic purinergic (P2Y) receptors to pathological pain is controversial. In the present study, using single cell RT-PCR (reverse transcription-polymerase chain reaction) and single cell nested-PCR techniques, we examined the expression of P2X2, P2X3, P2Y1 and P2Y2 mRNA transcripts in retrogradely labeled cutaneous sensory neurons from mouse lumber dorsal root ganglia (DRGs) following peripheral inflammation. The percentage of cutaneous sensory neurons expressing P2Y2 mRNA transcripts increased after complete Freund’s adjuvant (CFA) treatment. Particularly, the P2Y2 mRNA transcripts were more frequently detected in small-diameter cutaneous neurons from CFA-treated mice than those from control mice. Coexpression of P2Y2 and P2X (P2X2 or P2X3) mRNAs was more frequently observed in cutaneous sensory neurons from CFA-treated mice relative to controls. Pain behavioral tests showed that the blockade of P2Y receptors by suramin attenuated mechanical allodynia evoked either by CFA or uridine triphosphate (UTP), an endogenous P2Y2 and P2Y4 agonist. These results suggest that chronic inflammatory pain enhances expression of P2Y2 receptor in peripheral sensory neurons that innervate the injured tissue and the activation of P2Y receptors contributes to mechanical allodynia following inflammation.
KeywordsInflammatory pain Purinergic receptor P2Y Single cell PCR
This work was supported by the National Natural Science Foundation of China (81100822), Zhejiang Provincial Natural Science Foundation of China (LY15H090011), Leading and top Talents Project of Ningbo City (ZX2012000399) and Sponsored by K.C.Wong Magna Fund in Ningbo University.
Conflict of interest
All authors declare that they have no conflicts of interest.
- Burnstock G (2014a) Physiopathological roles of p2x receptors in the central nervous system. Curr Med ChemGoogle Scholar
- Gerevich Z, Borvendeg SJ, Schroder W, Franke H, Wirkner K, Norenberg W, Furst S, Gillen C, Illes P (2004) Inhibition of N-type voltage-activated calcium channels in rat dorsal root ganglion neurons by P2Y receptors is a possible mechanism of ADP-induced analgesia. J Neurosci Off J Soc Neurosci 24:797–807CrossRefGoogle Scholar
- Kwon SG, Roh DH, Yoon SY, Moon JY, Choi SR, Choi HS, Kang SY, Han HJ, Beitz AJ, Lee JH (2014) Blockade of peripheral P2Y1 receptors prevents the induction of thermal hyperalgesia via modulation of TRPV1 expression in carrageenan-induced inflammatory pain rats: involvement of p38 MAPK phosphorylation in DRGs. Neuropharmacology 79:368–379CrossRefPubMedGoogle Scholar
- Moriyama T, Iida T, Kobayashi K, Higashi T, Fukuoka T, Tsumura H, Leon C, Suzuki N, Inoue K, Gachet C, Noguchi K, Tominaga M (2003) Possible involvement of P2Y2 metabotropic receptors in ATP-induced transient receptor potential vanilloid receptor 1-mediated thermal hypersensitivity. J Neurosci Off J Soc Neurosci 23:6058–6062Google Scholar
- Xiao HS, Huang QH, Zhang FX, Bao L, Lu YJ, Guo C, Yang L, Huang WJ, Fu G, Xu SH, Cheng XP, Yan Q, Zhu ZD, Zhang X, Chen Z, Han ZG, Zhang X (2002) Identification of gene expression profile of dorsal root ganglion in the rat peripheral axotomy model of neuropathic pain. Proc Natl Acad Sci U S A 99:8360–8365PubMedCentralCrossRefPubMedGoogle Scholar