Chronic musculoskeletal pain conditions are maladaptive and negatively impact the lives of over 100 million American. A growing body of literature suggests that these pain conditions are linked to abnormalities in pathways regulating the bioavailability of catecholamines. Patients with common chronic pain conditions such as fibromyalgia and temporomandibular disorder exhibit increased clinical and experimental pain, coupled with decreased levels of the enzyme catechol-O-methyltransferase (COMT), which metabolizes catecholamines to their inactive derivatives.
Previously, our lab has shown that b2- and b3 adrenergic receptors (ARs) are important for the develpoment of COMT-dependent pain. However, recent evidence suggests, that while b2- and b3 ARs play an important role in the development of COMT-dependent pain, these receptors may not be as critical for the maintenance of COMT-dependent pain. Preliminary evidence demonstrates that instead, downstream inflammatory mediators (e.g., cytokines and mitoge activated protein kinases) residing in both central and peripheral tissue may maintain these pain states. Therefore, using molecular, pharmocological, and behavioral techniques, I investigate the role of inflammatory mediators in pain, and the moleculare signatures of enhanced pain sensitivity.
Sustained Stimulation of β2- and β3-adrenergic Receptors Leads to Persistent Functional Pain and Neuroinflammation.
Zhang X, Hartung JE, Bortsov A, Kim S, O’Buckley SC, Kozlowski J, Nackley AG.
Brain, Behavior, and Immunity. 2018 June 20 [Epub ahead of print].
Circulating Omentin-1 and Chronic Painful Temporomandibular Disorders.
Harmon JB, Sanders AE, Wilder RS, Essick GK, Slade GD, Hartung JE, Nackley AG.
J Oral Facial Pain Headache. 2016 Summer;30(3):203-209.
Nuclear factor-kappa B regulates pain and COMT expression in a rodent model of inflammation.
Hartung JE, Eskew O, Wong T, Tchivileva IE, Oladosu FA, O’Buckley SC, Nackley AG.
Brain Behav Immun. 2015 Nov;50:196-202. Epub 2015 Jul 15.
β2- and β3-adrenergic receptors drive COMT-dependent pain by increasing production of nitric oxide and cytokines.
Hartung JE, Ciszek BP, Nackley AG.
Pain. 2014 Jul;155(7):1346-55. Epub 2014 Apr 13.