DOI: 10.2337/db23-478-p ISSN: 0012-1797

478-P: Brain Volume Changes after Long-Term Opioid Treatment in Painful Diabetic Peripheral Neuropathy

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Aim: Opioid medications are commonly used to treat Painful-Diabetic Peripheral Neuropathy (Painful-DPN). However, opioids are associated with significant adverse effects, including prescription opioid use disorder which has reached epidemic proportions in the United States. There is an urgent need to determine the effect of long-term opioid treatment (>6-months) on cerebral structure in Painful-DPN.

Methods: A total of 56 participants with Painful-DPN were recruited (17 on long-term opioid treatment [O+] and 39 not on opioid treatment [O-]). Participants underwent detailed clinical and neurophysiological assessments and cerebral imaging (3T, Phillips Medical Systems, Holland). Brain morphometric analysis was performed using Freesurfer.

Results: O+ participants were prescribed: codeine (n=3, 18%), tramadol (n=5, 29%), morphine modified release (n=1, 6%), buprenorphine (n=1, 6%), and combination treatment (n=5, 29%). O+ participants had a longer duration of diabetes, greater HbA1c, higher pain severity and higher scores on Hospital Anxiety and Depression scales compared to the O- group. Participants in the O+ group had a greater mean caudate volume (O+ 3.5mL ± 0.4; O- 3.2 ± 0.4mL, p=0.034); mean insula volume (O+ 6.3 ± 0.8; O- 5.9 ± 0.6, p=0.049) and mean insular vertices (O+ 3,286 ± 411; O- 3055 ± 282, p=0.018).

Conclusion: This is the first study to examine the impact of long-term opioid use on cerebral structure in Painful-DPN. Our findings suggest that chronic opioid use may alter affective/attentional pain processing (insular cortex) and brain regions associated with binge/intoxication (caudate nucleus). These results may have important clinical implications for uncovering the effects of long-term prescription opioid use on brain structure in Painful-DPN. Clearer clinical utility will come from future longitudinal modelling of the prognostic characteristics of opioid use disorder from the neuroimaging features identified in this study.


G.P.Sloan: None. K.Teh: None. P.Shillo: None. S.Tesfaye: Advisory Panel; Bayer Inc., Wörwag Pharma GmbH & Co. KG, Angelini, Speaker's Bureau; Viatris Inc., Nevro Corp., Procter & Gamble, Novo Nordisk, Berlin-Chemie AG. D.Selvarajah: None. I.D.Wilkinson: None.


European Foundation for the Study of Diabetes; Novartis Knowledge Exchange Support Fund (X/162218); Efficacy and Mechanism Evaluation Programme (NIHR129921); Medical Research Council/National Institute for Health Research Partnership

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