title: Chronic Back Pain Is Associated with Alterations in Dopamine Neurotransmission in the Ventral Striatum.
abstract: Back pain is common in the general population, but only a subgroup of back pain patients develops a disabling chronic pain state. The reasons for this are incompletely understood, but recent evidence implies that both preexisting and pain-related variations in the structure and function of the nervous system may contribute significantly to the development of chronic pain. Here, we addressed the role of striatal dopamine (DA) D2/D3 receptor (D2/D3R) function in chronic non-neuropathic back pain (CNBP) by comparing CNBP patients and healthy controls using PET and the D2/D3R-selective radioligand [(11)C]raclopride. D2/D3R availability was measured at baseline and during a pain challenge, yielding in vivo measures of receptor availability (binding potential, BPND) and DA release (change in BPND from baseline to activated state). At baseline, CNBP patients demonstrated reductions in D2/D3R BPND in the ventral striatum compared with controls. These reductions were associated with greater positive affect scores and pain tolerance measures. The reductions in D2/D3R BPND were also correlated with μ-opioid receptor BPND and pain-induced endogenous opioid system activation in the amygdala, further associated with measures of positive affect, the affective component of back pain and pain tolerance. During the pain challenge, lower magnitudes of DA release, and therefore D2/D3R activation, were also found in the ventral striatum in the CNBP sample compared with controls. Our results show that CNBP is associated with adaptations in ventral striatal D2/D3R function, which, together with endogenous opioid system function, contribute to the sensory and affective-motivational features of CNBP.
  
  
  CONCLUSIONS
  The neural systems that underlie chronic pain remain poorly understood. Here, using PET, we provide insight into the molecular mechanisms that regulate sensory and affective dimensions of pain in chronic back pain patients. We found that patients with back pain have alterations in brain dopamine function that are associated with measures of pain sensitivity and affective state, but also with brain endogenous opioid system functional measures. These findings suggest that brain dopamine-opioid interactions are involved in the pathophysiology of chronic pain, which has potential therapeutic implications. Our results may also help to explain individual variation in susceptibility to opioid medication misuse and eventual addiction in the context of chronic pain.
authors.affiliation: Molecular and Behavioral Neuroscience Institute.
authors.forename: Ilkka K
authors.initials: IK
authors.lastname: Martikainen
authors.affiliation: Molecular and Behavioral Neuroscience Institute, Neuroscience Graduate Program, University of Michigan, Ann Arbor, Michigan 48104, and.
authors.forename: Emily B
authors.initials: EB
authors.lastname: Nuechterlein
authors.affiliation: Molecular and Behavioral Neuroscience Institute, Department of Psychiatry.
authors.forename: Marta
authors.initials: M
authors.lastname: Peciña
authors.affiliation: Molecular and Behavioral Neuroscience Institute, Department of Psychiatry.
authors.forename: Tiffany M
authors.initials: TM
authors.lastname: Love
authors.affiliation: Molecular and Behavioral Neuroscience Institute.
authors.forename: Chelsea M
authors.initials: CM
authors.lastname: Cummiford
authors.affiliation: Department of Anesthesiology, Department of Obstetrics and Gynecology, Department of Health Management and Policy, School of Public Health, and.
authors.forename: Carmen R
authors.initials: CR
authors.lastname: Green
authors.affiliation: College of Dental Medicine, Columbia University, New York, New York 10032.
authors.forename: Christian S
authors.initials: CS
authors.lastname: Stohler
authors.affiliation: Molecular and Behavioral Neuroscience Institute, Department of Psychiatry, Department of Radiology, University of Michigan, Ann Arbor, Michigan 48109, zubieta@umich.edu.
authors.forename: Jon-Kar
authors.initials: JK
authors.lastname: Zubieta
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000493:pharmacokinetics; D001416:Back Pain / Q000473:pathology*; D001931:Brain Mapping; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D002908:Chronic Disease; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D005260:Female; D005283:Fentanyl / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D010147:Pain Measurement; D011485:Protein Binding / Q000187:drug effects; D020891:Raclopride / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*; D066328:Ventral Striatum / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D002250:Carbon Radioisotopes; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D020891:Raclopride; C017114:carfentanil; D005283:Fentanyl; D004298:Dopamine
keywords: amygdala; chronic pain; dopamine; endogenous opioid; striatum