Articles on NFCI (peer-reviewed scientific papers)
The following are a collection of peer-reviewed scientific papers on NFCI or closely related topics. They are grouped according to general topics and some papers appear under more than one category. This is not an exhaustive list, most papers published prior to 1970 have been omitted due to their limited accessibility.
Potential treatments for NFCI and cold sensitivity
NFCI in non-military populations
Animal studies - models of NFCI
NFCI review papers
Castellani JW, Eglin CM, Ikäheimo TI, Montgomery H, Paal P, Tipton MJ (2021) ACSM Expert Consensus Statement: Injury Prevention and Exercise Performance during Cold-Weather Exercise. Current Sports Medicine Reports 20:594-607 https://doi.org/10.1249/jsr.0000000000000907
Francis TJ, Golden FS. (1985) Non-freezing cold injury: the pathogenesis. J R Nav Med Serv. 71(1):3-8.
Francis TJ. (1984) Non freezing cold injury: a historical review. J R Nav Med Serv. 70(3):134-9.
Haman, F., Souza, S.C., Castellani, J.W., Dupuis, M.P., Friedl, K.E., Sullivan-Kwantes, W. and Kingma, B.R., (2022). Human vulnerability and variability in the cold: Establishing individual risks for cold weather injuries. Temperature, pp.1-38 https://doi.org/10.1080/23328940.2022.2044740
Heil K, Thomas R, Robertson G, Porter A, Milner R, Wood A. (2016) Freezing and non-freezing cold weather injuries: a systematic review. Br Med Bull. 117(1):79-93. https://doi.org/10.1093/bmb/ldw001
Heil KM, Oakley EH, Wood AM. (2016) British Military freezing cold injuries: a 13-year review. J R Army Med Corps. 162(6):413-418. https://doi.org/10.1136/jramc-2015-000445
Imray C, Grieve A, Dhillon S. (2009) Cold damage to the extremities: frostbite and non-freezing cold injuries. Postgrad Med J. 85:481–488 https://doi.org/10.1136/pgmj.2008.068635
Imray CH, Oakley EH. (2005) Cold still kills: cold-related illnesses in military practice freezing and non-freezing cold injury. J R Army Med Corps. 151:218–222 https://doi.org/10.1136/jramc-151-04-02
Imray CH, Richards P, Greeves J, Castellani JW. (2011) Nonfreezing cold-induced injuries. J R Army Med Corps 157: 79–84. https://doi.org/10.1136/jramc-157-01-14
Mills WJ Jr, Mills WJ 3rd. (1993) Peripheral non-freezing cold injury: immersion injury. Alaska Med. 35:117–128.
Ministry of Defence (2021) JSP 539: Heat illness and cold injury: medical management. Part 2 guidance. London, MoD 2021.
Mistry K, Ondhia C, Levell NJ. (2020) A review of trench foot: a disease of the past in the present. Clin Exp Dermatol.45(1):10-14. https://doi.org/10.1111/ced.14031 .
Oakley EH (2009). The hidden enemy: non-freezing cold injury since the Falklands Conflict. NATO, TRO, HFM-168 Symp "Soldiers Cold Environment”: 20–22 April 2009. NATO, TRO: Helsinki, Finland; 2009. The hidden enemy: non-freezing cold injury since the Falklands Conflict. KN2-1-7.
Tipton M, Eglin C (2023) Non-Freezing Cold Injury: a little-known big problem. Experimental Physiology 108:329-30 https://doi.org/10.1113/EP091139
Tipton MJ, Corbett J, Eglin CM, Mekjavic IB, Montgomery H (2020) In pursuit of the unicorn. Exp Physiol, 106, 385-8 https://doi.org/10.1113/EP089147
Tlougan BE, Mancini AJ, Mandell JA, Cohen DE, Sanchez MR (2011) Skin Conditions in Figure Skaters, Ice-Hockey Players and Speed Skaters. Sport Med, 41, 967–84. https://doi.org/10.2165/11592190-000000000-00000
Ungley CC, Channell GD & Richards RL (1945). The immersion foot syndrome. Br J Surg, 33, 17–31. https://doi.org/10.1580/1080-6032(2003)014[0135:tifs]2.0.co;2
Epidemiology of NFCI
Burgess JE, Macfarlane F. (2009) Retrospective analysis of the ethnic origins of male British army soldiers with peripheral cold weather injury. J R Army Med Corps. 155:11–15. https://doi.org/10.1136/jramc-155-01-04
Cattermole TJ. (1999) The epidemiology of cold injury in Antarctica. Aviat Space Environ Med. 70:135–140.
DeGroot DW, Castellani JW, Williams JO, Amoroso PJ. (2003) Epidemiology of U.S. Army cold weather injuries, 1980–1999. Aviat Space Environ Med. 74:564–570
Donnell FLO & Taubman SB (2016). Update: Cold weather injuries, active component US Armed Forces, July 2011 - June 2016. Med Surveill Mon Rep.
Heil KM, Oakley EH, Wood AM. (2016) British Military freezing cold injuries: a 13-year review. J R Army Med Corps. 162(6):413-418. https://doi.org/10.1136/jramc-2015-000445
Kuht JA, Woods D & Hollis S (2018). Case series of non-freezing cold injury: epidemiology and risk factors. J R Army Med Corps, 165, 400-4. https://doi.org/10.1136/jramc-2018-000992
Oakley, B., Brown, H. L., Johnson, N., & Bainbridge, C. (2022). Nonfreezing cold injury and cold intolerance in paddlesport. Wilderness & Environmental Medicine, 33(2), 187-196. https://doi.org/10.1016/j.wem.2022.03.003
Williamson K, Izard R. (2007) Epidemic of non-freezing cold injury in the British Army. J R Army Med Corps. 2007 Jun;153(2):143. Erratum in: J R Army Med Corps. 2007 Sep;153(3):183.
Vascular aspects of NFCI
Ahle NW, Buroni JR, Sharp MW & Hamlet MP (1990). Infrared thermographic measurement of circulatory compromise in trenchfoot-injured Argentine soldiers. Aviat Space Env Med, 61, 247–250.
Arvesen A, Rosen L, Eltvik LP, Kroese A & Stranden E (1994). Skin microcirculation in patients with sequelae from local cold injuries. Int J Microcirc Clin Exp, 14, 335–342. https://doi.org/10.1159/000178852
Carlsson, D., Pettersson, H., Burström, L., Nilsson, T., & Wahlström, J. (2016). Neurosensory and vascular function after 14 months of military training comprising cold winter conditions. Scandinavian Journal of Work, Environment & Health, 61-70. https://doi.org/10.5271/sjweh.3530
Eglin CM, Golden F & Tipton MJ (2013). Cold sensitivity test for individuals with non-freezing cold injury: the effect of prior exercise. Extrem Physiol Med, 2, 16. https://extremephysiolmed.biomedcentral.com/track/pdf/10.1186/2046-7648-2-16.pdf
Eglin, C. M., Wright, J. A., Maley, M., Hollis, S., Massey, H., Montgomery, H., & Tipton, M. J. (2023). The peripheral vascular responses in non-freezing cold injury and matched controls. Experimental Physiology 108:420-437. https://doi.org/10.1113/EP090721
Endrich B, Hammersen F, Messmer K. (1990) Microvascular ultrastructure in non-freezing cold injuries. Res Exp Med (Berl). 190(5):365-79. https://doi.org/10.1007/BF00000043 .
Golden FSC, Francis TJR, Gallimore D & Pethybridge R (2013). Lessons from history: morbidity of cold injury in the Royal Marines during the Falklands Conflict of 1982. Extrem Physiol Med, 2, 23. https://doi.org/10.1186/2046-7648-2-23
Stephens JP, Laight DW, Golden FStC, Tipton M (2009) Damage to vascular endothelium and smooth muscle contribute to the development of non-freezing cold injury in the rat tail vascular bed in vitro. Proceedings from the International Conference on Environmental Ergonomics, Boston, p177-181.
Ungley CC, Channell GD & Richards RL (1945). The immersion foot syndrome. Br J Surg, 33, 17–31. https://doi.org/10.1580/1080-6032(2003)014[0135:tifs]2.0.co;2
Ungley, C. C., & Blackwood, W. (1942). Peripheral vasoneuropathy after chilling" immersion foot and immersion hand". The Lancet, 240(6216), 447-451. https://doi.org/10.1016/S0140-6736(00)58135-5
Neural aspects of NFCI
Anand P, Privitera R, Donatien P, Misra VP, Woods DR. (2021) Capsaicin 8% Patch Treatment in Non-Freezing Cold Injury: Evidence for Pain Relief and Nerve Regeneration. Front Neurol. 12:722875. https://doi.org/10.3389/fneur.2021.722875
Anand P, Privitera R, Yiangou Y, Donatien P, Birch R & Misra P (2017). Trench Foot or Non-Freezing Cold Injury As a Painful Vaso-Neuropathy: Clinical and Skin Biopsy Assessments. Front Neurol, 8, 514. https://doi.org/10.3389/fneur.2017.00514
Carlsson, D., Burström, L., Heldestad Lilliesköld, V., Nilsson, T., Nordh, E., & Wahlström, J. (2014). Neurosensory sequelae assessed by thermal and vibrotactile perception thresholds after local cold injury. International Journal of Circumpolar Health, 73(1), 23540. https://doi.org/10.3402/ijch.v73.23540
Carlsson, D., Pettersson, H., Burström, L., Nilsson, T., & Wahlström, J. (2016). Neurosensory and vascular function after 14 months of military training comprising cold winter conditions. Scandinavian Journal of Work, Environment & Health, 61-70. https://doi.org/10.5271/sjweh.3530
Geng Z, Tong X, Jia H. (2015) Reactive oxygen species (ROS) mediates non-freezing cold injury of rat sciatic nerve. Int J Clin Exp Med. 8(9):15700-7 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc4658954/
Golden FSC, Francis TJR, Gallimore D & Pethybridge R (2013). Lessons from history: morbidity of cold injury in the Royal Marines during the Falklands Conflict of 1982. Extrem Physiol Med, 2, 23. https://doi.org/10.1186/2046-7648-2-23
Irwin MS, Sanders R, Green CJ, Terenghi G. (1997) Neuropathy in non-freezing cold injury (trench foot). J R Soc Med 1997; 90: 433–8. https://doi.org/10.1177/014107689709000805
Irwin MS. (1996) Nature and mechanism of peripheral nerve damage in an experimental model of non-freezing cold injury. Ann R Coll Surg Engl. 78(4):372-9. https://pubmed.ncbi.nlm.nih.gov/8712655
Jia J, Pollock M, Jia J. (1989) Cold injury to nerves is not due to ischaemia alone. Brain. 121 ( Pt 5):989-1001. https://doi.org/10.1093/brain/121.5.989
Jia J, Pollock M. (1997) The pathogenesis of non-freezing cold nerve injury. Observations in the rat. Brain 120: 631–46. https://doi.org/10.1093/brain/120.4.631
Jørum E & Opstad P-K (2019). A 4-year follow-up of non-freezing cold injury with cold allodynia and neuropathy in 26 naval soldiers. Scand J Pain, 19, 441–451. https://doi.org/10.1515/sjpain-2019-0035
Kennett RP, Gilliatt RW. (1991) Nerve conduction studies in experimental non-freezing cold injury: I. Local nerve cooling. Muscle Nerve.14(6):553-62. https://doi.org/10.1002/mus.880140610.
Kennett RP, Gilliatt RW. (1991) Nerve conduction studies in experimental non-freezing cold injury: II. Generalized nerve cooling by limb immersion. Muscle Nerve. 14(10):960-7. https://doi.org/10.1002/mus.880141006.
Krøigård, T., Wirenfeldt, M., Svendsen, T. K., & Sindrup, S. H. (2018). Asymptomatic loss of intraepidermal nerve fibers with preserved thermal detection thresholds after repeated exposure to severe cold. Brain and Behavior, 8(3), e009147. https://doi.org/10.1002/brb3.917
Nukada H, Pollock M, Allpress S. (1981) Experimental cold injury to peripheral nerve. Brain. 104(Pt 4):779-811. https://doi.org/10.1093/brain/104.4.779
Ungley CC, Channell GD & Richards RL (1945). The immersion foot syndrome. Br J Surg, 33, 17–31. https://doi.org/10.1580/1080-6032(2003)014[0135:tifs]2.0.co;2
Ungley, C. C., & Blackwood, W. (1942). Peripheral vasoneuropathy after chilling" immersion foot and immersion hand". The Lancet, 240(6216), 447-451. https://doi.org/10.1016/S0140-6736(00)58135-5
Vale TA, Symmonds M, Polydefkis M, Byrnes K, Rice ASC, Themistocleous AC & Bennett DLH (2017). Chronic non-freezing cold injury results in neuropathic pain due to a sensory neuropathy. Brain, 140, 2557–2569. https://doi.org/10.1093/brain/awx215
Wright, J. Massey, H., Hollis, S., Vale, T., Bennett, D., Maley, M., Montgomery, H., Tipton, M.J., Eglin, C.M (2022) Peripheral sensory function in non-freezing cold injury patients and matched controls. Experimental Physiol 108:438-447 https://doi.org/10.1113/EP090720
Blood biomarkers of NFCI
Eglin CM, Wright JA, Shepherd AI, Massey H, Hollis S, Towse J, Young JS, Maley M, Bailey S, Wilkinson C, Montgomery H & Tipton MJ (2023). Plasma biomarkers of endothelial function, inflammation and oxidative stress in individuals with non-freezing cold injury. Experimental Physiology 108:448-64. https://doi.org/10.1113/EP090722
Potential treatments for NFCI and cold sensitivity
Anand P, Privitera R, Donatien P, Misra VP, Woods DR. (2021) Capsaicin 8% Patch Treatment in Non-Freezing Cold Injury: Evidence for Pain Relief and Nerve Regeneration. Front Neurol. 12:722875. https://doi.org/10.3389/fneur.2021.722875
Das, D. K., Iyengar, J., Jones, R. M., Lu, D., & Maity, S. (1991). Protection from nonfreezing cold injury by quinacrine, a phospholipase inhibitor. Cryobiology, 28(2), 177–184. http://www.ncbi.nlm.nih.gov/pubmed/2070620
Eglin CM, Costello JT, Bailey SJ, Gilchrist M, Massey H & Shepherd AI (2017). Effects of dietary nitrate supplementation on the response to extremity cooling and endothelial function in individuals with cold sensitivity. A double blind, placebo controlled, crossover, randomised control trial. Nitric Oxide, 70, 76–85. https://doi.org/10.1016/j.niox.2017.09.005
Hope K, Eglin C, Golden F & Tipton M (2014). Sublingual glyceryl trinitrate and the peripheral thermal responses in normal and cold-sensitive individuals. Microvasc Res, 91, 84–89. https://doi.org/10.1016/j.mvr.2013.11.002
Ionescu AM, Hutchinson S, Ahmad M, Imray C. (2017) Potential new treatment for non-freezing cold injury: is Iloprost the way forward? J R Army Med Corps. 163(5):361-363. https://doi.org/10.1136/jramc-2016-000672
Li H, Zhang L, Xu M. (2016) Dexamethasone prevents vascular damage in early-stage non-freezing cold injury of the sciatic nerve. Neural Regen Res. 11(1):163-7. https://doi.org/10.4103/1673-5374.175064
Tam A, Lyons T, Vennam S, Barnes R, Imray C. (2022) Early Use of Iloprost in Nonfreezing Cold Injury. Wilderness Environ Med. 33(3):344-347. https://doi.org/10.1016/j.wem.2022.04.009
NFCI case studies
Fraser IC, Loftus JA. (1979) “Trench foot” caused by the cold. Br Med J. 1(6169):1017. https://doi.org/10.1136/bmj.1.6169.1017
Ionescu AM, Hutchinson S, Ahmad M, Imray C. (2017) Potential new treatment for non-freezing cold injury: is Iloprost the way forward? J R Army Med Corps. 163(5):361-363. https://doi.org/10.1136/jramc-2016-000672
Irwin MS, Sanders R, Green CJ, Terenghi G. (1997) Neuropathy in non-freezing cold injury (trench foot). J R Soc Med 1997; 90: 433–8. https://doi.org/10.1177/014107689709000805
King RC, Parrish JA, Allibone A. (1958) Trench-foot in peacetime England. Br Med J. 1(5079):1099–1102. https://doi.org/10.1136/bmj.1.5079.1099
Laden GD, Purdy G, O’Rielly G (2007) Cold injury to a diver’s hand after a 90-min dive in 6 degrees C water. Aviat Sp Env Med, 78, 523–5.
Marcus P. (1979) “Trench foot” caused by the cold. Br Med J. 1(6163):622. https://doi.org/10.1136/bmj.1.6163.622
Paal P, Brugger H, Kaser G, Putzer G, Tiefenthaler W, Wenzel V (2013) Surviving 6 days in a crevasse. Lancet, 381, 506. https://www.sciencedirect.com/science/article/pii/S0140673612620327
Parsons, S., Leach, I.H., Charnley, R.M. (1993). A case of bilateral trench foot. Injury, 24, 680-1.
Ramstead KD, Hughes RG, Webb AJ. (1980) Recent cases of trench foot. Postgrad Med J. 56:879–883. https://doi.org/10.1136/pgmj.56.662.879
Williams, G., Morgan, A., Harvey, J. (2005) Trench foot following a collapse: assessment of the feet is essential in the elderly. Age and Aging, 34, 651-2.
NFCI in non-military populations
Cattermole TJ. (1999) The epidemiology of cold injury in Antarctica. Aviat Space Environ Med. 70:135–140.
Fraser IC, Loftus JA. (1979) “Trench foot” caused by the cold. Br Med J. 1(6169):1017. https://doi.org/10.1136/bmj.1.6169.1017
Laden GD, Purdy G, O’Rielly G (2007) Cold injury to a diver’s hand after a 90-min dive in 6 degrees C water. Aviat Sp Env Med, 78, 523–5.
Longman DP, Brown EL, Imray CHE (2020) Nonfreezing cold injuries among long-distance Polar rowers. Wilderness Environ Med, 31, 209-214. https://doi.org/10.1016/j.wem.2019.12.009
Marcus P. (1979) “Trench foot” caused by the cold. Br Med J. 1(6163):622. https://doi.org/10.1136/bmj.1.6163.622
Oakley, B., Brown, H. L., Johnson, N., & Bainbridge, C. (2022). Nonfreezing cold injury and cold intolerance in paddlesport. Wilderness & Environmental Medicine, 33(2), 187-196. https://doi.org/10.1016/j.wem.2022.03.003
Paal P, Brugger H, Kaser G, Putzer G, Tiefenthaler W, Wenzel V (2013) Surviving 6 days in a crevasse. Lancet, 381, 506. https://doi.org/10.1186/s13049-016-0303-7
Parsons, S., Leach, I.H., Charnley, R.M. (1993). A case of bilateral trench foot. Injury, 24, 680-1.
Ramstead KD, Hughes RG, Webb AJ. (1980) Recent cases of trench foot. Postgrad Med J. 56:879–883. https://doi.org/10.1136/pgmj.56.662.879
Tlougan BE, Mancini AJ, Mandell JA, Cohen DE, Sanchez MR (2011) Skin Conditions in Figure Skaters, Ice-Hockey Players and Speed Skaters. Sport Med, 41, 967–84. https://doi.org/10.2165/11592190-000000000-00000
Williams, G., Morgan, A., Harvey, J. (2005) Trench foot following a collapse: assessment of the feet is essential in the elderly. Age and Aging, 34, 651-2.
Animal studies - models of NFCI
Das, D. K., Iyengar, J., Jones, R. M., Lu, D., & Maity, S. (1991). Protection from nonfreezing cold injury by quinacrine, a phospholipase inhibitor. Cryobiology, 28(2), 177–184. http://www.ncbi.nlm.nih.gov/pubmed/2070620
Geng Z, Tong X, Jia H. (2015) Reactive oxygen species (ROS) mediates non-freezing cold injury of rat sciatic nerve. Int J Clin Exp Med. 8(9):15700-7 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc4658954/
Irwin MS. (1996) Nature and mechanism of peripheral nerve damage in an experimental model of non-freezing cold injury. Ann R Coll Surg Engl. 78(4):372-9. https://pubmed.ncbi.nlm.nih.gov/8712655
Jia J, Pollock M, Jia J. (1989) Cold injury to nerves is not due to ischaemia alone. Brain. 121 ( Pt 5):989-1001. https://doi.org/10.1093/brain/121.5.989
Jia J, Pollock M. (1997) The pathogenesis of non-freezing cold nerve injury. Observations in the rat. Brain 120: 631–46. https://doi.org/10.1093/brain/120.4.631
Kennett RP, Gilliatt RW. (1991) Nerve conduction studies in experimental non-freezing cold injury: I. Local nerve cooling. Muscle Nerve.14(6):553-62. https://doi.org/10.1002/mus.880140610.
Kennett RP, Gilliatt RW. (1991) Nerve conduction studies in experimental non-freezing cold injury: II. Generalized nerve cooling by limb immersion. Muscle Nerve. 14(10):960-7. https://doi.org/10.1002/mus.880141006.
Li H, Jia JP, Xu M, Zhang L. (2015) Changes in the blood-nerve barrier after sciatic nerve cold injury: indications supporting early treatment. Neural Regen Res. 10(3):419-24. doi: 10.4103/1673-5374.153690.
Li H, Zhang L, Xu M. (2016) Dexamethasone prevents vascular damage in early-stage non-freezing cold injury of the sciatic nerve. Neural Regen Res. 11(1):163-7. https://doi.org/10.4103/1673-5374.175064
Nukada H, Pollock M, Allpress S. (1981) Experimental cold injury to peripheral nerve. Brain. 104(Pt 4):779-811. https://doi.org/10.1093/brain/104.4.779
Stephens JP, Laight DW, Golden FStC, Tipton M (2009) Damage to vascular endothelium and smooth muscle contribute to the development of non-freezing cold injury in the rat tail vascular bed in vitro. Proceedings from the International Conference on Environmental Ergonomics, Boston, p177-181.
Cold sensitivity (without NFCI)
Davey M, Eglin CM, House JR & Tipton M (2013). The contribution of blood flow to the skin temperature responses during a cold sensitivity test. Eur J Appl Physiol, 113, 2411–2417. http://dx.doi.org/10.1007/s00421-013-2678-8
Eglin C (2011). Cold sensitivity in windsurfers ed. Kounalakis SN & Koskolou M. XIV International Conference on Environmental Ergonomics 47–48.
Eglin CM, Costello JT, Bailey SJ, Gilchrist M, Massey H & Shepherd AI (2017). Effects of dietary nitrate supplementation on the response to extremity cooling and endothelial function in individuals with cold sensitivity. A double blind, placebo controlled, crossover, randomised control trial. Nitric Oxide, 70, 76–85. https://doi.org/10.1016/j.niox.2017.09.005
Eglin CM, Costello JT, Tipton MJ & Massey HC (2020) Previous recreational cold exposure does not alter endothelial function or sensory thermal thresholds in the hands or feet. Exp Physiol, 106, 328-337. https://doi.org/10.1113/EP088555
Hope K, Eglin C, Golden F & Tipton M (2014). Sublingual glyceryl trinitrate and the peripheral thermal responses in normal and cold-sensitive individuals. Microvasc Res, 91, 84–89. https://doi.org/10.1016/j.mvr.2013.11.002
House CM, Taylor RJ & Oakley EHN (2015). Repeatability of a cold stress test to assess cold sensitization. Occup Med, 65, 578–584. https://doi.org/10.1093/occmed/kqv111
Ethnicity and NFCI/extremity responses to cooling
Burgess JE, Macfarlane F. (2009) Retrospective analysis of the ethnic origins of male British army soldiers with peripheral cold weather injury. J R Army Med Corps. 155:11–15. https://doi.org/10.1136/jramc-155-01-04
Maley MJ, Eglin CM, House JR & Tipton MJ (2014). The effect of ethnicity on the vascular responses to cold exposure of the extremities. Eur J Appl Physiol, 114, 2369–2379. https://doi.org/10.1007/s00421-014-2962-2
Maley MJ, House JR, Tipton MJ & Eglin CM (2017). Role of cyclooxygenase in the vascular response to locally delivered acetylcholine in Caucasian and African descent individuals. Microvasc Res, 111, 80–87. https://doi.org/10.1016/j.mvr.2017.01.005
Maley, M.J., House, J.R., Tipton, M.J. & Eglin CM (2015) Vascular responses of the extremities to transdermal application of vasoactive agents in Caucasian and African descent individuals. Eur J Appl Physiol, 115, 1801–1811. https://doi.org/10.1007/s00421-015-3164-2