Mol Pain
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Recently discovered neuropeptide S (NPS) has anxiolytic and pain-inhibiting effects in rodents. We showed previously that NPS increases synaptic inhibition of amygdala output to inhibit pain behaviors. The amygdala plays a key role in emotional-affective aspects of pain. ⋯ The inhibitory effect was blocked by a selective NPSR antagonist ([D-Cys(tBu)5]NPS). In conclusion, nasal application of NPS can inhibit emotional-affective, but not sensory, pain-related behaviors through an action in the amygdala. The beneficial effects of non-invasive NPS application may suggest translational potential.
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Substance P is an important neuropeptide released from nociceptors to mediate pain signals. We recently revealed antinociceptive signaling by substance P in acid-sensing ion channel 3 (ASIC3)-expressing muscle nociceptors in a mouse model of acid-induced chronic widespread pain. However, methods to specifically trigger the substance P antinociception were still lacking. ⋯ Acid could mediate a prolonged antinociceptive signaling via the release of substance P from muscle afferent neurons in a non-ASIC3, non-TRPV1 manner.
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The participation of spinal P2X receptors in neuropathic pain is well recognized. However, the role of P2Y receptors has been less studied. The purpose of this study was to investigate the contribution of spinal P2Y6,11 receptors following peripheral nerve damage induced by spinal nerve ligation. In addition, we determined the expression of P2Y6,11 receptors in the dorsal spinal cord in presence of the selective P2Y6,11 receptors antagonists. Furthermore, we evaluated the participation of spinal microglia and astrocytes in the pronociceptive role of P2Y6,11 receptors. ⋯ Our data suggest that spinal P2Y6 is present in spinal microglia while P2Y11 receptors are present in both spinal microglia and astrocytes, and both receptors are up-regulated in rats subjected to spinal nerve injury. In addition, our data suggest that the spinal P2Y6 and P2Y11 receptors participate in the maintenance of neuropathic pain.