title: Reward deficiency and anti-reward in pain chronification.
abstract: Converging lines of evidence suggest that the pathophysiology of pain is mediated to a substantial degree via allostatic neuroadaptations in reward- and stress-related brain circuits. Thus, reward deficiency (RD) represents a within-system neuroadaptation to pain-induced protracted activation of the reward circuits that leads to depletion-like hypodopaminergia, clinically manifested anhedonia, and diminished motivation for natural reinforcers. Anti-reward (AR) conversely pertains to a between-systems neuroadaptation involving over-recruitment of key limbic structures (e.g., the central and basolateral amygdala nuclei, the bed nucleus of the stria terminalis, the lateral tegmental noradrenergic nuclei of the brain stem, the hippocampus and the habenula) responsible for massive outpouring of stressogenic neurochemicals (e.g., norepinephrine, corticotropin releasing factor, vasopressin, hypocretin, and substance P) giving rise to such negative affective states as anxiety, fear and depression. We propose here the Combined Reward deficiency and Anti-reward Model (CReAM), in which biopsychosocial variables modulating brain reward, motivation and stress functions can interact in a 'downward spiral' fashion to exacerbate the intensity, chronicity and comorbidities of chronic pain syndromes (i.e., pain chronification).
authors.affiliation: Center for Pain and the Brain, Boston Children's Hospital and Massachusetts General Hospitals, USA; Department of Anesthesia, Critical Care and Pain Medicine, Boston Children's Hospital, USA; Department of Psychiatry, Mclean and Massachusetts General Hospital, USA; Harvard Medical School, Boston MA, USA. Electronic address: david.borsook@childrens.harvard.edu.
authors.forename: D
authors.initials: D
authors.lastname: Borsook
authors.affiliation: Center for Pain and the Brain, Boston Children's Hospital and Massachusetts General Hospitals, USA; Department of Anesthesia, Critical Care and Pain Medicine, Boston Children's Hospital, USA; Harvard Medical School, Boston MA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Linnman
authors.affiliation: Center for Pain and the Brain, Boston Children's Hospital and Massachusetts General Hospitals, USA; Department of Anesthesia, Critical Care and Pain Medicine, Boston Children's Hospital, USA; Department of Psychology, Uppsala University, Uppsala, Sweden; Harvard Medical School, Boston MA, USA.
authors.forename: V
authors.initials: V
authors.lastname: Faria
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Hospital, USA; Harvard Medical School, Boston MA, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Strassman
authors.affiliation: Center for Pain and the Brain, Boston Children's Hospital and Massachusetts General Hospitals, USA; Department of Anesthesia, Critical Care and Pain Medicine, Boston Children's Hospital, USA; Department of Psychiatry, Mclean and Massachusetts General Hospital, USA; Harvard Medical School, Boston MA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Becerra
authors.affiliation: Department of Psychiatry, Boonshoft School of Medicine, Wright State University and Dayton VA Medical Center, Dayton, OH, USA.
authors.forename: I
authors.initials: I
authors.lastname: Elman
mesh_terms: D000679:Amygdala; D001921:Brain; D003346:Corticotropin-Releasing Hormone; D009042:Motivation; D010146:Pain; D012201:Reward
chemical_list: D003346:Corticotropin-Releasing Hormone
keywords: Addiction; Amygdala; Analgesia; Aversion; Dopamine; Habenula; Motivation; Nucleus accumbens; Pain; Reward; Stress