| First Author | Vicente-Rodríguez M | Year | 2013 |
| Journal | Pharmacol Biochem Behav | Volume | 110 |
| Pages | 185-91 | PubMed ID | 23891830 |
| Mgi Jnum | J:325950 | Mgi Id | MGI:6872693 |
| Doi | 10.1016/j.pbb.2013.07.013 | Citation | Vicente-Rodriguez M, et al. (2013) Genetic inactivation of pleiotrophin but not midkine potentiates clonidine-induced alpha-2 adrenergic-mediated analgesia. Pharmacol Biochem Behav 110:185-91 |
| abstractText | Genetic deletion of the heparin-binding cytokines pleiotrophin (PTN) or midkine (MK) potentiates morphine-induced antinociceptive effects in animal models. Despite the known interactions between the opioid and noradrenergic systems in the control of pain, the possible roles of PTN and/or MK in analgesia induced by agonists of alpha2-adrenergic receptors remained to be studied. We have now tested the antinociceptive effects of the alpha2-adrenergic receptor agonist clonidine in female PTN genetically deficient (PTN-/-), MK genetically deficient (MK-/-) and wild type (WT+/+) mice. We did not find differences among genotypes in the hot-plate test, an assay in which supraspinal and spinal mechanisms contribute to nociceptive responses, suggesting that endogenous expression of PTN and MK is not key in the analgesia induced by clonidine in this test. In contrast, we found that clonidine-induced analgesia was significantly enhanced in PTN-/- mice compared to MK-/- and WT+/+ mice in the tail-immersion test. Interestingly, the alpha2-adrenergic antagonist yohimbine prevented clonidine-induced analgesia in the tail immersion test in all the 3 genotypes. The data suggest that the spinal antinociceptive effects caused by stimulation of alpha2-adrenoceptors are differentially regulated by endogenous expression of PTN. |
