Supplemental Digital Content is Available in the Text. Validated questionnaires revealed a shift of attention from chronic pain towards the COVID-19 pandemic in patients with chronic painful polyneuropathy.

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Pain relief after capsaicin application was associated with functional recovery of peptidergic nociceptors upon functional laser speckle contrast analysis instead of their degeneration.

Chronic pain is a constantly recurring and persistent illness, presenting a formidable healthcare challenge for patients and physicians alike. Current first‐line analgesics offer only low‐modest efficacy when averaged across populations, further contributing to this debilitating disease burden. Moreover, many recent trials for novel analgesics have not met primary efficacy endpoints, which is particularly striking considering the pharmacological advances have provided a range of highly relevant new drug targets. Heterogeneity within chronic pain cohorts is increasingly understood to play a critical role in these failures of treatment and drug discovery, with some patients deriving substantial benefits from a given intervention while it has little‐to‐no effect on others. As such, current treatment failures may not result from a true lack of efficacy, but rather a failure to target individuals whose pain is driven by mechanisms which it therapeutically modulates. This necessitates a move towards phenotypical stratification of patients to delineate responders and non‐responders in a mechanistically driven manner. In this article, we outline a bench‐to‐bedside roadmap for this transition to mechanistically informed personalised pain medicine. We emphasise how the successful identification of novel analgesics is dependent on rigorous experimental design as well as the validity of models and translatability of outcome measures between the animal model and patients. Subsequently, we discuss general and specific aspects of human trial design to address heterogeneity in patient populations to increase the chance of identifying effective analgesics. Finally, we show how stratification approaches can be brought into clinical routine to the benefit of patients.image

Background Previous studies investigated cold‐evoked potentials (CEPs) for the assessment of the integrity of cold‐mediating A‐delta fibres and the spinothalamic tract. Nevertheless, several methodological questions remained unanswered to proceed to clinical application. How do latencies and amplitudes vary between CEPs and contact heat‐evoked potentials (CHEPs)? Are there differences between variable and fixed thermode positions or between glabrous and hairy skin? Are CEPs recordable in patients with abnormal cold processing? Methods A total of 16 healthy subjects were tested with CEPs and CHEPs at the face, hand and foot. Variable and fixed thermode positions, hairy and glabrous skin were compared. Three patients with abnormal cold processing were tested with CEPs and quantitative sensory testing. Results Compared to CEPs, CHEPs latencies were significantly longer at all locations, amplitudes were significantly larger at the face and the hand whilst comparable at the foot. CEPs and CHEPs did not differ significantly between variable and fixed thermode positions using inter stimulus intervals of 8–12 s. CEP latencies were increased by around 20% at the glabrous skin. Patients with known abnormal cold processing (central pain, polyneuropathy, Fabry's disease) showed increased N2 latencies as compared to normal controls. Conclusions Inter stimulus intervals of 8‐12 s allow the use of a fixed thermode position for reliable CEPs/CHEPs recording. Hairy skin stimulation results in faster latencies as compared to glabrous skin, without influencing EP amplitudes. In patients with abnormal cold processing, CEPs are recordable and increased latencies may be expected as compared to healthy controls and the healthy contralateral side. Significance Cold‐evoked potentials are an innovative, non‐invasive technique to assess cold detection and processing objectively. This study shows that CEP can be recorded from the hairy and glabrous skin, regardless of using fixed or variable thermode positions. Loss of A‐delta fibre function leads to an increased CEP latency, consistent with loss of cold detection in the QST.