Finally, a role for P2Y12R has been postulated in neuropathic pain, which is often caused by chronic diseases such as cancer. It has been shown that peripheral nerve injury was able to increase the expression of different ATP P2Y receptors, including P2Y12, in microglial cells present in the spinal dorsal horn (Kobayashi et al., 2008, 2012). More recently, in a rat model of tongue cancer pain, obtained by inoculation of squamous cell carcinoma cells, a marked activation of microglia through P2Y12R was found in the trigeminal spinal subnucleus caudalis. This resulted to be associated with increased excitability of nociceptive neurons and consequent allodynia after mechanical stimulation. The administration of the P2Y12 antagonist MRS2395 strongly reduced the “nocifensive” behavior and microglial activation in these animals (Tamagawa et al., 2016).