Clinical management of chronic pain, including pain related to temporomandibular disorders (TMD), has been challenging in part because a considerable number of chronic pain patients have accompanying psychological and psychiatric comorbidities in which depression is a major contributing factor. While clinical depression has long been linked to chronic pain and antidepressants are commonly used in chronic pain management, the mechanisms underlying the comorbidity between depression and chronic pain remain unclear. To date, there has been a lack of preclinical models that co-express depression and orofacial pain behaviors in same animals. Our recent experiments showed that TMD pain behaviors induced by complete Freund's adjuvant were exacerbated in a subset of Wistar-Kyoto (WKY) rats, a genetic variant of Wistar rats with demonstrable depression behavior, as compared with normal Wistar rats absent of depression behavior. Moreover, melatonin administered into the anterior cingular cortex prevented the exacerbation of TMD pain behaviors with a concurrent improvement of depression behavior in WKY rats. These preliminary results suggest that comparing pain behaviors in animals with and without depression behavior could be a useful approach to investigate the relationship between depression and chronic pain and to explore new treatment options for both depression and chronic pain. Thus, the goals of this application are 1) to explore and evaluate animal models that co-express orofacial pain and depression behaviors and 2) to use the animal model and a new pharmacological approach to examine whether improving depression behavior would result in a concurrent reduction of pain behaviors. We will use behavioral and pharmacological tools, in situ hybridization, immunocytochemistry, Western blot, real-time RT-PCR, and enzyme-linked immunosorbent assay to accomplish three specific aims: 1) to explore and evaluate animal models of combined depression and TMD pain behaviors; 2) to examine the effects of melatonin on depression and TMD pain behaviors; and 3) to examine changes in the melatonin level and brain melatonin receptor expression in relation to depression and TMD pain behaviors. The successful completion of this work will provide important information on a new preclinical model that could be used to examine interactions between depression and chronic pain and to search for novel therapeutic strategies for treating both chronic pain and depression. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE018538-02
Application #
7456580
Study Section
Special Emphasis Panel (ZDE1-YL (41))
Program Officer
Kusiak, John W
Project Start
2007-07-01
Project End
2012-06-30
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
2
Fiscal Year
2008
Total Cost
$396,708
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Mi, Wenli; Wang, Shuxing; You, Zerong et al. (2017) Nortriptyline Enhances Morphine-Conditioned Place Preference in Neuropathic Rats: Role of the Central Noradrenergic System. Anesth Analg 125:1032-1041
Rusanescu, Gabriel; Mao, Jianren (2014) Notch3 is necessary for neuronal differentiation and maturation in the adult spinal cord. J Cell Mol Med 18:2103-16
Chen, Kelly Yan; Chen, Lucy; Mao, Jianren (2014) Buprenorphine-naloxone therapy in pain management. Anesthesiology 120:1262-74
Zhang, Shuzhuo; Jin, Xu; You, Zerong et al. (2014) Persistent nociception induces anxiety-like behavior in rodents: role of endogenous neuropeptide S. Pain 155:1504-15
Song, Li; Wang, Shuxing; Zuo, Yunxia et al. (2014) Midazolam exacerbates morphine tolerance and morphine-induced hyperactive behaviors in young rats with burn injury. Brain Res 1564:52-61
Li, Na; Lim, Grewo; Chen, Lucy et al. (2013) Spinal expression of Hippo signaling components YAP and TAZ following peripheral nerve injury in rats. Brain Res 1535:137-47
Ma, Yuxin; Wang, Shuxing; Tian, Yinghong et al. (2013) Disruption of persistent nociceptive behavior in rats with learning impairment. PLoS One 8:e74533
Kim, Hyangin; Chen, Lucy; Lim, Grewo et al. (2012) Brain indoleamine 2,3-dioxygenase contributes to the comorbidity of pain and depression. J Clin Invest 122:2940-54
Wang, Shuxing; Tian, Yinghong; Song, Li et al. (2012) Exacerbated mechanical hyperalgesia in rats with genetically predisposed depressive behavior: role of melatonin and NMDA receptors. Pain 153:2448-57
Mao, Jianren (2012) Current challenges in translational pain research. Trends Pharmacol Sci 33:568-73

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