Ventromedial prefrontal neurokinin 1 receptor availability is reduced in chronic pain

Linnman, Clas; Appel, Lieuwe; Furmark, Tomas; Söderlund, Anne; Gordh, Torsten; Långström, Bengt; Fredrikson, Mats

doi:10.1016/j.pain.2010.01.008

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Volume 149, Issue 1 , Pages 64-70, April 2010

Ventromedial prefrontal neurokinin 1 receptor availability is reduced in chronic pain

Clas Linnman
- Department of Psychology, Uppsala University, Uppsala, Sweden
- Corresponding author. Address: 7 Grove Street, apt 9, Boston, MA 02114, USA. Tel.: +1 857 284 28 16; fax: +1 617 726 4029.
Lieuwe Appel
- Uppsala Imanet AB, GE Healthcare, Uppsala, Sweden
Tomas Furmark
- Department of Psychology, Uppsala University, Uppsala, Sweden
Anne Söderlund
- Department of Physiotherapy, School of Health, Care and Social Welfare, Mälardalen University, Västerås, Sweden
- Section of Physiotherapy, Department of Neuroscience, Uppsala University, Sweden
Torsten Gordh
- Laboratory of Pain Research, Department of Surgical Sciences, Division of Anaesthesiology and Intensive Care Medicine, Uppsala University Hospital, Sweden
Bengt Långström
- Department of Biochemistry and Organic Chemistry, Uppsala University, Sweden
- Neuropsychopharmacology Section, Faculty of Medicine, Imperial College, London, UK
Mats Fredrikson
- Department of Psychology, Uppsala University, Uppsala, Sweden

Received 9 August 2009; received in revised form 30 December 2009; accepted 12 January 2010. published online 05 February 2010.

Abstract

Neurokinin 1 (NK1) receptors are involved in pain and anxiety behaviors in animals, but little is known about central alterations in this receptor system in human pain. With positron emission tomography, using a [11]-Carbon labeled NK1 receptor antagonist, we demonstrate attenuated NK1 receptor availability in frontal, insular and cingulate cortex, as well as the hippocampus, amygdala and the periaqueductal gray area in patients with chronic pain. The reduced availability was most pronounced in the ventromedial prefrontal cortex (vmPFC), where attenuations correlated to measures of fear and avoidance of movement. Further, vmPFC NK1 levels also displayed opposing influences in patients as compared to controls on regional cerebral blood flow in the anterior cingulate. We conclude that the central NK1 receptor system is altered in human chronic pain. The results suggest that NK1 receptors in the vmPFC modulate motor inhibition, and contribute to fear and avoidance of movement.

Keywords: Chronic pain, Ventromedial prefrontal cortex, Neurokinin 1, Substance P, PET, Whiplash, Avoidance