title: Sex differences in a Murine Model of Complex Regional Pain Syndrome.
abstract: Complex Regional Pain Syndrome (CRPS) is a major cause of chronic pain after surgery or trauma to the limbs. Despite evidence showing that the prevalence and severity of many forms of chronic pain, including CRPS, differ between males and females, laboratory studies on sex-related differences in animal models of CRPS are not available, and the impact of sex on the transition from acute to chronic CRPS pain and disability are unexplored. Here we make use of a tibia fracture/cast mouse model that recapitulates the nociceptive, functional, vascular, trophic, inflammatory and immune aspects of CRPS. Our aim is to describe the chronic time course of nociceptive, motor and memory changes associated with fracture/cast in male and female mice, in addition to exploring their underlying spinal mechanisms. Our behavioral data shows that, compared to males, female mice display lower nociceptive thresholds following fracture in the absence of any differences in ongoing or spontaneous pain. Furthermore, female mice show exaggerated signs of motor dysfunction, deficits in fear memory, and latent sensitization that manifests long after the normalization of nociceptive thresholds. Our biochemical data show differences in the spinal cord levels of the glutamate receptor NR2b, suggesting sex differences in mechanisms of central sensitization that could account for differences in duration and severity of CRPS symptoms between the two groups.
authors.affiliation: Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, United States; Department of Anesthesiology, Stanford University School of Medicine, Stanford, CA, United States; Palo Alto Institute of Research and Education, Palo Alto, CA, United States. Electronic address: maral@stanford.edu.
authors.forename: Maral
authors.initials: M
authors.lastname: Tajerian
authors.affiliation: Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, United States; Department of Anesthesiology, Stanford University School of Medicine, Stanford, CA, United States; Palo Alto Institute of Research and Education, Palo Alto, CA, United States.
authors.forename: Peyman
authors.initials: P
authors.lastname: Sahbaie
authors.affiliation: Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, United States; Palo Alto Institute of Research and Education, Palo Alto, CA, United States.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Palo Alto Institute of Research and Education, Palo Alto, CA, United States; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, United States.
authors.forename: David
authors.initials: D
authors.lastname: Leu
authors.affiliation: Palo Alto Institute of Research and Education, Palo Alto, CA, United States; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, United States.
authors.forename: Hsun Yu
authors.initials: HY
authors.lastname: Yang
authors.affiliation: Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, United States; Department of Anesthesiology, Stanford University School of Medicine, Stanford, CA, United States; Palo Alto Institute of Research and Education, Palo Alto, CA, United States.
authors.forename: Wenwu
authors.initials: W
authors.lastname: Li
authors.affiliation: Palo Alto Institute of Research and Education, Palo Alto, CA, United States; Geriatrics Research Education and Clinical Center, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, United States; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, United States.
authors.forename: Ting Ting
authors.initials: TT
authors.lastname: Huang
authors.affiliation: Physical Medicine and Rehabilitation Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, United States.
authors.forename: Wade
authors.initials: W
authors.lastname: Kingery
authors.affiliation: Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, United States; Department of Anesthesiology, Stanford University School of Medicine, Stanford, CA, United States; Palo Alto Institute of Research and Education, Palo Alto, CA, United States.
authors.forename: J
authors.initials: J
authors.lastname: David Clark
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D059333:Central Nervous System Sensitization / Q000502:physiology*; D020918:Complex Regional Pain Syndromes / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D005239:Fear / Q000502:physiology; D005260:Female; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D000068079:Motor Disorders / Q000209:etiology / Q000503:physiopathology; D017288:Pain Threshold / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012737:Sex Factors; D013116:Spinal Cord / Q000378:metabolism*
chemical_list: C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate
keywords: Central sensitization; Chronic pain; Complex regional pain syndrome; Pain-related memory deficits; Sex differences in pain