The neurocognitive effects of 5 day anesthetic ketamine for the treatment of refractory complex regional pain syndrome

Koffler, Sandra P.; Hampstead, Benjamin M.; Irani, Farzin; Tinker, Jennifer; Kiefer, Ralph-Thomas; Rohr, P.; Schwartzman, Robert J.

doi:10.1016/j.acn.2007.05.005

Cited by 57 publications

(40 citation statements)

References 33 publications

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“…For instance, there is evidence of anxiety 49,50 and attention deficits 51–55 in rodent models of pain, in addition to changes in mood 50,56,57 and overall cognitive function 58–60 . Similar to what is seen in patients, 61 some of these conditions subside once the pain is ameliorated. 62 We have shown that selective signs of neophobic anxiety (in the form of altered thigmotaxis in the zero maze but not open field assay) and memory impairment (novel object recognition and social memory but not novel location recognition) are present in our fracture/cast mice.…”

Section: Discussionsupporting

confidence: 73%

Brain Neuroplastic Changes Accompany Anxiety and Memory Deficits in a Model of Complex Regional Pain Syndrome

Tajerian

Leu²,

Zou³

et al. 2014

Anesthesiology

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Background Complex regional pain syndrome (CRPS) is a painful condition with ~50,000 annual new cases in the United States. It is a major cause of work-related disability, chronic pain after limb fractures and persistent pain after extremity surgery. Additionally, CRPS patients often experience cognitive changes, anxiety and depression. The supraspinal mechanisms linked to these CRPS-related comorbidities remain poorly understood. Methods We used a previously-characterized mouse model of tibia fracture/cast immobilization showing the principal stigmata of CRPS (n=8–20/group) observed in humans. Our central hypothesis was that fracture/cast mice manifest changes in measures of thigmotaxis (indicative of anxiety) and working memory reflected in neuroplastic changes in amygdala, perirhinal cortex, and hippocampus. Results We demonstrate that nociceptive sensitization in these mice is accompanied by altered thigmotactic behaviors in the zero maze but not open field assay, and working memory dysfunction in novel object recognition and social memory but not in novel location recognition. Furthermore, we found evidence of structural changes and synaptic plasticity including changes in dendritic architecture and decreased levels of synaptophysin and brain derived neurotrophic factor in specific brain regions. Conclusions Our findings provide novel observations regarding behavioral changes and brain plasticity in a mouse model of CRPS. In addition to elucidating some of the supraspinal correlates of the syndrome, this work supports the potential use of therapeutic interventions that not only directly target sensory input and other peripheral mechanisms, but also attempt to ameliorate the broader pain experience by modifying its associated cognitive and emotional comorbidities.

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Section: Discussionsupporting

confidence: 73%

Brain Neuroplastic Changes Accompany Anxiety and Memory Deficits in a Model of Complex Regional Pain Syndrome

Tajerian

Leu²,

Zou³

et al. 2014

Anesthesiology

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“…In other reports following anesthetic doses of ketamine, improvement in pain and other neuropsychologial evaluation at 6 weeks post treatment were reported, albeit these were not controlled trials (Koffler et al 2007). Nevertheless there may be lessons from other diseases that affect the brain it is noteworthy that acute ketamine doses seems to reverse depression (Machado-Vieira et al 2009) and ketamine decreased prevalence of post-traumatic stress disorder (PTSD) in soldiers receiving ketamine during their surgery for treatment of their burns (McGhee et al 2008).…”

Section: Lack Of Effect On Functional Activity - Lessons From Other Dmentioning

confidence: 99%

Ketamine and chronic pain – Going the distance

Borsook¹

2009

Pain

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“…Furthermore, clear alterations in cognition, memory and emotions (anxiety and depression) in CRPS sufferers have been demonstrated [73–78], potentially due to diminished GABAergic or NMDA-mediated cortical neuroplasticity [79]. It is notable that these changes appear to be reversible: for instance, ketamine treatment was associated with improved CRPS symptoms, as well as improvements in cognition [80]. …”

Section: Introductionmentioning

confidence: 99%

New Concepts in Complex Regional Pain Syndrome

Tajerian

Clark

2016

Hand Clinics

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SYNOPSIS Despite the severe pain and disability associated with Complex Regional Pain Syndrome (CRPS), our lack of understanding of the pathophysiological mechanisms supporting this enigmatic condition prevents the rational design of new therapies, a situation that is frustrating both to the physician and the patient. The following review will highlight some of the mechanisms thought to be involved in the pathophysiology of CRPS in preclinical models and CRPS patients, with the ultimate goal that understanding these mechanisms will lead to the design of efficacious, mechanism-based treatments available to the clinic.

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The neurocognitive effects of 5 day anesthetic ketamine for the treatment of refractory complex regional pain syndrome

Cited by 57 publications

References 33 publications

Brain Neuroplastic Changes Accompany Anxiety and Memory Deficits in a Model of Complex Regional Pain Syndrome

Brain Neuroplastic Changes Accompany Anxiety and Memory Deficits in a Model of Complex Regional Pain Syndrome

Ketamine and chronic pain – Going the distance

New Concepts in Complex Regional Pain Syndrome

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