TY - JOUR
T1 - Chronic non-freezing cold injury results in neuropathic pain due to a sensory neuropathy
AU - Vale, Tom A.
AU - Symmonds, Mkael
AU - Polydefkis, Michael
AU - Byrnes, Kelly
AU - Rice, Andrew S.C.
AU - Themistocleous, Andreas C.
AU - Bennett, David L.H.
N1 - Funding Information:
This work was supported by grants from the UK Ministry of Defence and The Wellcome Trust. D.L.H.B. is a Senior Wellcome Trust Clinical Scientist (ref. no. 095698z/11/z and 202747/Z/16/Z). A.C.T. is supported by the International Diabetic Neuropathy Consortium (IDNC) research programme, and is an Honorary Research Fellow of the Brain Function Research Group, School of Physiology, Faculty of Health Science, University of Witwatersrand. T.A.V. is supported by a grant from the UK Ministry of Defence. Neither the Wellcome Trust nor the UK Ministry of Defence played a role in the study design, patient recruitment, data analysis, data interpretation, or the preparation of the manuscript.
Funding Information:
Study participants were enrolled into one of two studies. Actively serving British army personnel were enrolled in the ‘Neurological consequences of non-freezing cold injury’ study approved by the Ministry of Defence Research Ethics Committee (MoDREC Protocol No: 616/MoDREC/14). Ex-servicemen (veterans) were enrolled in the ‘Pain in Neuropathy Study (PiNS)’ (Themistocleous et al., 2016), approved by the National Research Ethics Service of the United Kingdom (No: 10/H0706/35). Study participants were recruited from a specialist neuropathy clinic at The John Radcliffe Hospital, Oxford UK, or through self-referral via advertising. All study participants signed written consent before participation.
Publisher Copyright:
© The Author (2017).
PY - 2017/10/1
Y1 - 2017/10/1
N2 - Non-freezing cold injury develops after sustained exposure to cold temperatures, resulting in tissue cooling but not freezing. This can result in persistent sensory disturbance of the hands and feet including numbness, paraesthesia and chronic pain. Both vascular and neurological aetiologies of this pain have been suggested but remain unproven. We prospectively approached patients referred for clinical assessment of chronic pain following non-freezing cold injury between 12 February 2014 and 30 November 2016. Of 47 patients approached, 42 consented to undergo detailed neurological evaluations including: questionnaires to detail pain location and characteristics, structured neurological examination, quantitative sensory testing, nerve conduction studies and skin biopsy for intraepidermal nerve fibre assessment. Of the 42 study participants, all had experienced non-freezing cold injury while serving in the UK armed services and the majority were of African descent (76.2%) and male (95.2%). Many participants reported multiple exposures to cold. The median time between initial injury and referral was 3.72 years. Pain was principally localized to the hands and the feet, neuropathic in nature and in all study participants associated with cold hypersensitivity. Clinical examination and quantitative sensory testing were consistent with a sensory neuropathy. In all cases, large fibre nerve conduction studies were normal. The intraepidermal nerve fibre density was markedly reduced with 90.5% of participants having a count at or below the 0.05 centile of published normative controls. Using the Neuropathic Pain Special Interest Group of the International Association for the Study of Pain grading for neuropathic pain, 100% had probable and 95.2% definite neuropathic pain. Chronic nonfreezing cold injury is a disabling neuropathic pain disorder due to a sensory neuropathy. Why some individuals develop an acute painful sensory neuropathy on sustained cold exposure is not yet known, but individuals of African descent appear vulnerable. Screening tools, such as the DN4 questionnaire, and treatment algorithms for neuropathic pain should now be used in the management of these patients.
AB - Non-freezing cold injury develops after sustained exposure to cold temperatures, resulting in tissue cooling but not freezing. This can result in persistent sensory disturbance of the hands and feet including numbness, paraesthesia and chronic pain. Both vascular and neurological aetiologies of this pain have been suggested but remain unproven. We prospectively approached patients referred for clinical assessment of chronic pain following non-freezing cold injury between 12 February 2014 and 30 November 2016. Of 47 patients approached, 42 consented to undergo detailed neurological evaluations including: questionnaires to detail pain location and characteristics, structured neurological examination, quantitative sensory testing, nerve conduction studies and skin biopsy for intraepidermal nerve fibre assessment. Of the 42 study participants, all had experienced non-freezing cold injury while serving in the UK armed services and the majority were of African descent (76.2%) and male (95.2%). Many participants reported multiple exposures to cold. The median time between initial injury and referral was 3.72 years. Pain was principally localized to the hands and the feet, neuropathic in nature and in all study participants associated with cold hypersensitivity. Clinical examination and quantitative sensory testing were consistent with a sensory neuropathy. In all cases, large fibre nerve conduction studies were normal. The intraepidermal nerve fibre density was markedly reduced with 90.5% of participants having a count at or below the 0.05 centile of published normative controls. Using the Neuropathic Pain Special Interest Group of the International Association for the Study of Pain grading for neuropathic pain, 100% had probable and 95.2% definite neuropathic pain. Chronic nonfreezing cold injury is a disabling neuropathic pain disorder due to a sensory neuropathy. Why some individuals develop an acute painful sensory neuropathy on sustained cold exposure is not yet known, but individuals of African descent appear vulnerable. Screening tools, such as the DN4 questionnaire, and treatment algorithms for neuropathic pain should now be used in the management of these patients.
KW - nerve conduction studies
KW - neuropathic pain
KW - peripheral nerve injury
KW - sensory neuropathy
KW - small fibre neuropathy
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U2 - 10.1093/brain/awx215
DO - 10.1093/brain/awx215
M3 - Article
C2 - 28969380
AN - SCOPUS:85030681657
SN - 0006-8950
VL - 140
SP - 2557
EP - 2569
JO - Brain
JF - Brain
IS - 10
ER -