A longitudinal study of paradoxical heat sensation in 420 individuals.

A paradoxical heat sensation (PHS) is the feeling of warmth when the skin is cooled. Paradoxical heat sensation is a pathological sign associated with neuropathy, eg, diabetic polyneuropathy (DPN). The aim of this study was to examine whether specific characteristics in the sensory nervous system are associated with PHS and to evaluate whether PHS is a predictor of thermal sensory loss or neuropathy. Using baseline and 5-year follow-up data from a study on patients with type 2 diabetes, we analyzed the relationship between PHS and sensory and neurophysiological parameters, assessed with quantitative sensory testing (QST), nerve conduction studies, and skin biopsy measures. A total of 420 individuals was included. Sixty-two individuals had diabetes without DPN, 263 had DPN of which 89 had painful DPN, and 95 were controls without diabetes. At baseline, the frequency of PHS was higher in patients with DPN (51%) than in controls (32%, P = 0.001, Pearson χ2 test), but there were no differences between patients with diabetes with and without DPN or between those with painful vs painless DPN (both P ≥ 0.085). Among individuals with normal baseline thermal sensation (defined from the QST normative material) (n = 161), PHS at baseline was associated with thermal sensory loss at follow-up (χ2 = 4.7, P = 0.03, logistic regression, joint test, adjusted for sex, age, and neuropathy status). Across all groups, participants with PHS exhibited thermal sensory loss. This is the first longitudinal study on PHS. We confirmed that PHS is related to thermal sensory loss. Furthermore, we demonstrated that PHS is an early marker of thermal sensory loss, which may have therapeutic or prophylactic implications.