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

Marshall, Anne, Kalteniece, Alise, Ferdousi, Maryam, Azmi, Shazli, Jude, Edward B, Adamson, Clare, D'Onofrio, Luca, Dhage, Shaishav, Soran, Handrean, Campbell, Jackie
et al (show 5 more authors) (2023) Spinal disinhibition: evidence for a hyperpathia phenotype in painful diabetic neuropathy. BRAIN COMMUNICATIONS, 5 (2). fcad051-.

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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 explore 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, 93 patients with diabetic neuropathy underwent testing of Hoffmann 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 Hoffmann reflex rate-dependent depression at 1, 2 and 3 Hz (<i>P</i> ≤ 0.001). Patients with painful diabetic neuropathy exhibited an overall loss of function profile on quantitative sensory testing. However, within the painful diabetic neuropathy group, cluster analysis showed evidence of greater spinal disinhibition associated with greater mechanical pain sensitivity, relative heat hyperalgesia and higher ratings of spontaneous burning pain. These findings support spinal disinhibition as an important centrally mediated pain amplification mechanism in painful diabetic neuropathy. Furthermore, our analysis indicates an association between spinal disinhibition and a distinct phenotype, arguably akin to hyperpathia, with combined loss and relative gain of function leading to increasing nociceptive drive.

Item Type: Article
Uncontrolled Keywords: diabetes, neuropathy, pain, spinal disinhibition, phenotype
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User: Symplectic Admin
Date Deposited: 12 May 2023 15:33
Last Modified: 31 May 2023 16:11
DOI: 10.1093/braincomms/fcad051
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3170261