The potential role of serotonergic mechanisms in the spinal oxytocin-induced antinociception |
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| Affiliation: | 1. School of Pharmacy, Shandong University, Jinan, Shandong Province, PR China;2. Department of Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, PR China;3. Department of Pharmacy, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong Province, PR China;4. School of Medicine, Shandong University, Jinan, Shandong Province, PR China;5. Department of Cardiovascular, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong Province, PR China;6. Department of Endocrinology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong Province, PR China;1. Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark;2. Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden;3. Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden;4. Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Vienna, Austria;1. Center for Inflammation, Translational and Clinical Lung Research, USA;2. BioQual Incorporated, 9600 Medical Center Dr., Rockville, MD 20850, USA;3. Temple University Flow Cytometry Facility, USA;4. Department of Neuroscience, Temple University School of Medicine, Philadelphia, PA 19140, USA;1. Department of Physiology and Pathology, School of Dentistry, São Paulo State University, Araraquara, SP, Brazil;2. School of Biotechnology, Southern Medical University, Guangzhou, China;3. Department of Physiology and Functional Genomics and McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, FL, USA |
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| Abstract: | The role of oxytocin (OXT) in pain modulation has been suggested. Indeed, hypothalamic paraventricular nuclei (PVN) electrical stimuli reduce the nociceptive neuronal activity (i.e., neuronal discharge associated with activation of Aδ- and C-fibers) of the spinal dorsal horn wide dynamic range (WDR) cells and nociceptive behavior. Furthermore, raphe magnus nuclei lesion reduces the PVN-induced antinociception, suggesting a functional interaction between the OXT and the serotoninergic system. The present study investigated in Wistar rats the potential role of spinal serotonergic mechanisms in the OXT- and PVN-induced antinociception. In long-term secondary mechanical allodynia and hyperalgesia induced by formalin or extracellular unitary recordings of the WDR cells we evaluated the role of 5-hydroxytryptamine (5-HT) effect on the OXT-induced antinociception. All drugs were given intrathecally (i.t.). OXT (1 × 10− 5–1 × 10− 4 nmol) or 5-HT (1 × 10− 3–1 × 10− 1 nmol) prevented the formalin-induced sensitization, an effect mimicked by PVN stimulation. Moreover, administration of OXT (1 × 10− 5 nmol) plus 5-HT (1 × 10− 3 nmol) at ineffective doses, produced antinociception. This effect was antagonized by: (i) d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH29]OVT (oxytocin receptor antagonist; 2 × 10− 2 nmol); or (ii) methiothepin (a non-specific 5-HT1/2/5/6/7 receptor antagonist; 80 nmol). Similar results were obtained with PVN stimulation plus 5-HT (5 × 10− 5 nmol). In WDR cell recordings, the PVN-induced antinociception was enhanced by i.t. 5-HT and partly blocked when the spinal cord was pre-treated with methiothepin (80 nmol). Taken together, these results suggest that serotonergic mechanisms at the spinal cord level are partly involved in the OXT-induced antinociception. |
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