The ADP receptor P2Y₁is necessary for normal thermal sensitivity in cutaneous polymodal nociceptors

• Main Authors: Jankowski Michael P, McIlwrath Sabrina L, Rau Kristofer K, Molliver Derek C, Koerber H Richard
• Format: Article
• Language: English
• Published: SAGE Publishing 2011-02-01
• Series: Molecular Pain
• Online Access: http://www.molecularpain.com/content/7/1/13

<p>Abstract</p> <p>Background</p> <p>P2Y₁is a member of the P2Y family of G protein-coupled nucleotide receptors expressed in peripheral sensory neurons. Using ratiometric calcium imaging of isolated dorsal root ganglion neurons, we found that the majority of neurons responding to adenosine diphosphate, the preferred endogenous ligand, bound the lectin IB4 and expressed the ATP-gated ion channel P2X₃. These neurons represent the majority of epidermal afferents in hairy skin, and are predominantly C-fiber polymodal nociceptors (CPMs), responding to mechanical stimulation, heat and in some cases cold.</p> <p>Results</p> <p>To characterize the function of P2Y₁in cutaneous afferents, intracellular recordings from sensory neuron somata were made using an <it>ex vivo </it>preparation in which the hindlimb skin, saphenous nerve, DRG and spinal cord were dissected in continuum, and cutaneous receptive fields characterized using digitally-controlled mechanical and thermal stimuli in male wild type mice. In P2Y₁-/- mice, CPMs showed a striking increase in mean heat threshold and a decrease in mean peak firing rate during a thermal ramp from 31-52°C. A similar change in mean cold threshold was also observed. Interestingly, mechanical testing of CPMs revealed no significant differences between P2Y₁-/- and WT mice.</p> <p>Conclusions</p> <p>These results strongly suggest that P2Y₁is required for normal thermal signaling in cutaneous sensory afferents. Furthermore, they suggest that nucleotides released from peripheral tissues play a critical role in the transduction of thermal stimuli in some fiber types.</p>