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Pain Rep. 2018 May 24;3(3):e651. doi: 10.1097/PR9.0000000000000651. eCollection 2018 May.

Neuropathic pain drives anxiety behavior in mice, results consistent with anxiety levels in diabetic neuropathy patients.

Author information

1
Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, MA, USA.
2
Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
3
Biobehavioral Pediatric Pain Lab, Boston Children's Hospital, Boston, MA, USA.
4
Department of Neurobiology, Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
5
Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
6
Brain Function Research Group, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
7
Pain Research Group, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital Campus, London, United Kingdom.
8
Diabetes Research Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom.
9
Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Abstract

Background:

Epidemiological studies in patients with neuropathic pain demonstrate a strong association with psychiatric conditions such as anxiety; however, the precipitating pathology between these symptoms remains unclear. To investigate this, we studied the effects of lifelong stress on levels of neuropathic pain-like behavior and conversely, the effects of chronic neuropathic injury on anxiety-like status in male and female mice. In addition, we assayed this link in painful and painless diabetic peripheral neuropathy patients.

Methods:

Male and female mice were subject to ongoing life-stress or control living conditions. Baseline sensitivity and anxiety tests were measured followed by spared nerve injury (SNI) to the sciatic nerve. Subsequent sensory testing occurred until 3 weeks after SNI followed by anxiety tests between 4 and 6 weeks after SNI.

Results:

Levels of tactile or cold allodynia did not differ between adult mice subject to lifelong chronic stress, relative to nonstressed controls, for at least 3 weeks after SNI. By contrast, longer-term neuropathic mice of both sexes displayed pronounced anxiety-like behavior, regardless of exposure to stress. If sex differences were present, females usually exhibited more pronounced anxiety-like behavior. These ongoing anxiety behaviors were corroborated with plasma corticosterone levels in distinct animal groups. In addition, data from patients with painful and nonpainful diabetic neuropathy showed a clear relationship between ongoing pain and anxiety, with females generally more affected than males.

Discussion:

Taken together, these data demonstrate a strong link between chronic neuropathic pain and chronic anxiety, with the driver of this comorbidity being neuropathic pain as opposed to on-going stress.

KEYWORDS:

Anxiety; Neuropathy; Pain; Sex differences; Spared nerve injury; Stress

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