Evaluating Spinal Inhibitory Dysfunction in Diabetes With Neuropathic Pain

doctor performing Hofmann reflex test on patient, neurology
doctor performing Hofmann reflex test on patient, neurology
Researchers sought to evaluate how impairment or loss of the Hoffman reflex may affect rates of painful diabetic neuropathy.

Impairment or loss of the Hoffmann reflex may aid in the identification of patients with painful diabetic neuropathy mediated by impaired spinal inhibitory systems, according to authors of a study published in Diabetes Care.

The researchers sought to evaluate how impaired rate-dependent depression of the Hoffman reflex (HRDD) may impact peripheral diabetic neuropathy rates in patients with diabetes. Researchers conducted this study in a large cohort of patients with type 1 or type 2 diabetes, both with and without neuropathic pain, to assess HRDD in conjunction with detailed peripheral structural and functional neuropathy phenotyping.

Patients with type 1 or type 2 diabetes, as well as those without diabetes in the control group, underwent nerve conduction studies and assessment of HRDD. Participants with an absent H-reflex were excluded. A total of 37 patients with type 1 diabetes, 67 patients with type 2 diabetes, and 34 healthy controls were enrolled.

Patients with type 1 diabetes were significantly younger and had a longer diabetes duration and lower body mass index (BMI) vs those with type 2 diabetes. No significant difference was noted in group mean HRDD among any of the study groups.

Compared with controls, all patients with diabetes were significantly older and had significantly higher BMIs and glycated hemoglobin (HbA1c) levels. Parameters for nerve conduction, cold detection threshold, warm detection threshold, vibration detection threshold, and corneal confocal microscopy were all significantly impaired in patients with diabetes vs controls, but there was no significant difference in either demographic or neuropathy parameters between patients with vs without painful diabetic neuropathy.

HRDD, however, was significantly impaired in patients with painful diabetic neuropathy vs those without it and controls. Conversely, HRDD was “significantly exaggerated” in patients with diabetes without pain vs controls. No significant difference in HRDD between those with mild and moderate-to-severe neuropathic pain was noted, nor was there a significant difference in HRDD between men and women with vs without pain or between men and women in the control group.

No significant correlation was made — across either the whole patient cohort or across the pain and no-pain groups — between HRDD and age, diabetes duration, BMI, HbA1c, or any measures of peripheral neuropathy. No significant correlation was seen in the control cohort between HRDD and either age or BMI.

Study limitations include fact that this was a cross-sectional study with fairly small cohorts. Also important was the significant age difference between the patient groups with diabetes and those in the control group, which may potentially affect the significance of neuropathy parameters between patients. Nevertheless, the researchers noted that “the patient cohorts with and without pain were well matched for age.”

The researchers concluded that their study shows “reduced and enhanced HRDD in patients with and without painful diabetic neuropathy, respectively, which was not associated with the presence or severity of diabetic neuropathy.”

Prospective and pharmacological intervention studies, they said, “are required to systematically address the utility of HRDD to target therapies in the clinic and for trial enrichment in clinical trials of new therapies for painful diabetic neuropathy.”


Worthington A, Kalteniece A, Ferdousi M, et al. Spinal inhibitory dysfunction in patients with painful or painless diabetic neuropathy. Diabetes Care. 2021;44(8):1835-1841. doi:10.2337/dc20-2797