Spinal disinhibition: evidence for a hyperpathia phenotype in painful diabetic neuropathy

Anne Marshall, Alise Kalteniece, Maryam Ferdousi, Shazli Azmi, Edward Jude, Clare Adamson, Luca D'Onofrio, Shaishav Dhage, Handrean Soran, Jackie Campbell, Corinne Lee-Kubli, Shaheen Hamdy, Rayaz A Malik, Nigel A Calcutt, Andrew Marshall*

*Corresponding author for this work

Research output: Contribution to JournalArticlepeer-review


The dominant sensory phenotype in patients with diabetic polyneuropathy and neuropathic pain is a loss of function. This raises questions as to which mechanisms underlie pain generation in the face of potentially reduced afferent input. One potential mechanism is spinal disinhibition, whereby a loss of spinal inhibition leads to increased ascending nociceptive drive due to amplification of, or a failure to suppress, incoming signals from the periphery. We aimed to determine whether a putative biomarker of spinal disinhibition, impaired rate dependent depression of the Hoffmann-reflex, is associated with a mechanistically appropriate and distinct pain phenotype in patients with painful diabetic neuropathy.
In this cross-sectional study, ninety-three patients with diabetic neuropathy underwent testing of H-reflex rate dependent depression and detailed clinical and sensory phenotyping, including quantitative sensory testing. Compared to neuropathic patients without pain, patients with painful diabetic neuropathy had impaired H-reflex rate dependent depression at 1, 2 and 3Hz (p=These findings support the hypothesis that spinal disinhibition is an important centrally mediated pain amplification mechanism in painful diabetic neuropathy and that abnormal H-reflex rate dependent depression is associated with a distinct phenotype, arguably akin to hyperpathia, with combined loss and relative gain of function leading to increasing nociceptive drive.
Original languageEnglish
Article numberfcad051
JournalBrain Communications
Issue number2
Publication statusPublished - 28 Feb 2023


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