• Merve Hazal Ser, Basak Yılmaz, Cem Sulu, Mustafa Sait Gönen, and Aysegul Gunduz.
• Neurology Department, Istanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, Istanbul, Fatih 34098, Turkey.
• Pain Med. 2023 Oct 3; 24 (10): 116111681161-1168.

BackgroundThe nociceptive flexion reflex (NFR) is a polysynaptic and multisegmental spinal reflex that develops in response to a noxious stimulus and is characterized by the withdrawal of the affected body part. The NFR possesses two excitatory components: early RII and late RIII. Late RIII is derived from high-threshold cutaneous afferent A-delta fibers, which are prone to injury early in the course of diabetes mellitus (DM) and may lead to neuropathic pain. We investigated NFR in patients with DM with different types of polyneuropathies to analyze the role of NFR in small fiber neuropathy (SFN).MethodsWe included 37 patients with DM and 20 healthy participants of similar age and sex. We performed the Composite Autonomic Neuropathy Scale-31, modified Toronto Neuropathy Scale, and routine nerve conduction studies. We grouped the patients into large fiber neuropathy (LFN), SFN, and no overt neurological symptom/sign groups. In all participants, NFR was recorded on anterior tibial (AT) and biceps femoris (BF) muscles after train stimuli on the sole of the foot, and NFR-RIII findings were compared.ResultsWe identified 11 patients with LFN, 15 with SFN, and 11 with no overt neurological symptoms or signs. The RIII response on the AT was absent in 22 (60%) patients with DM and 8 (40%) healthy participants. The RIII response on the BF was absent in 31 (73.8%) patients and 7 (35%) healthy participants (P = .001). In DM, the latency of RIII was prolonged, and the magnitude was reduced. Abnormal findings were seen in all subgroups; however, they were more prominent in patients with LFN compared to other groups.ConclusionsThe NFR-RIII was abnormal in patients with DM even before the emergence of the neuropathic symptoms. The pattern of involvement before neuropathic symptoms was possibly related to an earlier loss of A-delta fibers.© The Author(s) 2023. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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