It is well-recognized that, despite similar pain characteristics, some people with chronic pain recover, whereas others do not. In this review, we discuss possible contributions and interactions of biological, social, and psychological perturbations that underlie the evolution of treatment-resistant chronic pain. Behavior and brain are intimately implicated in the production and maintenance of perception. Our understandings of potential mechanisms that produce or exacerbate persistent pain remain relatively unclear. We provide an overview of these interactions and how differences in relative contribution of dimensions such as stress, age, genetics, environment, and immune responsivity may produce different risk profiles for disease development, pain severity, and chronicity. We propose the concept of “stickiness” as a soubriquet for capturing the multiple influences on the persistence of pain and pain behavior, and their stubborn resistance to therapeutic intervention. We then focus on the neurobiology of reward and aversion to address how alterations in synaptic complexity, neural networks, and systems (eg, opioidergic and dopaminergic) may contribute to pain stickiness. Finally, we propose an integration of the neurobiological with what is known about environmental and social demands on pain behavior and explore treatment approaches based on the nature of the individual's vulnerability to or protection from allostatic load.
aCenter for Pain and the Brain, Boston Children's Hospital, McLean and Massachusetts Hospitals, Boston, MA, United States
bDepartment of Anesthesia, Boston Children's Hospital, Boston, MA, United States
cDepartment of Psychiatry, McLean and Massachusetts Hospitals, Boston, MA, United States
dDepartment of Radiology, Massachusetts Hospital, Boston, MA, United States
eDepartment of Anesthesia, Stanford University, Palo Alto, CA, United States
fVeterans Administration, Dayton, OH, United States
gCentre for Pain Research, University of Bath, Bath, United Kingdom
hDepartment of Clinical and Health Psychology, Ghent University, Ghent, Belgium
Corresponding author. Address: Center for Pain and the Brain, Boston Children's Hospital, 1 Autumn St, Boston, MA 02115, United States. Tel.: 781-216-1982; fax: 617-730-0762. E-mail address: email@example.com (D. Borsook).
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
Received October 19, 2017
Received in revised form July 30, 2018
Accepted August 06, 2018