Changes in the analgesic mechanism of oxytocin can contribute to hyperalgesia in Parkinson's disease model rats

• Published in: PloS one Vol. 19; no. 8; p. e0300081
• Main Authors: Usami, Nayuka, Maegawa, Hiroharu, Hayashi, Masayoshi, Kudo, Chiho, Niwa, Hitoshi
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.08.2024; Public Library of Science (PLoS)
• Subjects: 6-Hydroxydopamine; Analgesics; Analgesics - pharmacology; Animals; Behavior; Biology and Life Sciences; Brain; c-Fos protein; Disease Models, Animal; Diseases; Dopamine receptors; Eph protein; Ethylenediaminetetraacetic acid; Experiments; Forebrain; Formaldehyde; Fos protein; Hormones; Hyperalgesia; Hyperalgesia - drug therapy; Hyperalgesia - metabolism; Japan; Laboratory animals; Locus coeruleus; Male; Medial forebrain bundle; Medicine and Health Sciences; Mesencephalon; Methamphetamine; Movement disorders; Neurodegenerative diseases; Neurons; Oxidopamine; Oxytocin; Oxytocin - pharmacology; Pain; Pain perception; Paraventricular Hypothalamic Nucleus - drug effects; Paraventricular Hypothalamic Nucleus - metabolism; Paraventricular nucleus; Parkinson Disease - drug therapy; Parkinson Disease - metabolism; Parkinson's disease; Periaqueductal gray area; Proto-Oncogene Proteins c-fos - metabolism; Rats; Rats, Sprague-Dawley; Research and Analysis Methods; Rubbing; Vibrissae; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0300081

Pain is a major non-motor symptom of Parkinson's disease (PD). Alterations in the descending pain inhibitory system (DPIS) have been reported to trigger hyperalgesia in PD patients. However, the underlying mechanisms remain unclear. In the current study, dopaminergic nigrostriatal lesions were induced in rats by injecting 6-hydroxydopamine (6-OHDA) into their medial forebrain bundle. The neural mechanisms underlying changes in nociception in the orofacial region of 6-OHDA-lesioned rats was examined by injecting formalin into the vibrissa pad. The 6-OHDA-lesioned rats were seen to exhibit increased frequency of face-rubbing and more c-Fos immunoreactive (c-Fos-IR) cells in the trigeminal spinal subnucleus caudalis (Vc), confirming hyperalgesia. Examination of the number of c-Fos-IR cells in the DPIS nuclei [including the midbrain ventrolateral periaqueductal gray, the locus coeruleus, the nucleus raphe magnus, and paraventricular nucleus (PVN)] showed that 6-OHDA-lesioned rats exhibited a significantly lower number of c-Fos-IR cells in the magnocellular division of the PVN (mPVN) after formalin injection compared to sham-operated rats. Moreover, the 6-OHDA-lesioned rats also exhibited significantly lower plasma oxytocin (OT) concentration and percentage of oxytocin-immunoreactive (OT-IR) neurons expressing c-Fos protein in the mPVN and dorsal parvocellular division of the PVN (dpPVN), which secrete the analgesic hormone OT upon activation by nociceptive stimuli, when compared to the sham-operated rats. The effect of OT on hyperalgesia in 6-OHDA-lesioned rats was examined by injecting formalin into the vibrissa pad after intracisternal administration of OT, and the findings showed a decrease in the frequency of face rubbing and the number of c-Fos-IR cells in the Vc. In conclusion, these findings confirm presence of hyperalgesia in PD rats, potentially due to suppression of the analgesic effects of OT originating from the PVN.