E. Velasco

The role of TRPA1 in the thermosensitivity of the corneal cold thermoreceptor nerve endings was studied in young and aged mice. The contribution of the TRPA1-dependent activity to basal tearing and thermally-evoked blink was also explored. The corneal cold thermoreceptors’ activity was recorded extracellularly in young (5-month-old) and aged (18-month-old) C57BL/6WT (WT) and TRPA1−/− knockout (TRPA1-KO) mice at basal temperature (34 °C) and during cooling (15 °C) and heating (45 °C) ramps. The blink response to cold and heat stimulation of the ocular surface and the basal tearing rate were also measured in young animals using orbicularis oculi muscle electromyography (OOemg) and phenol red threads, respectively. The background activity at 34 °C and the cooling- and heating-evoked responses of the cold thermoreceptors were similar in WT and TRPA1-KO animals, no matter the age. Similar to the aged WT mice, in the young and aged TRPA1-KO mice, most of the cold thermoreceptors presented low frequency background activity, a low cooling threshold, and a sluggish response to heating. The amplitude and duration of the OOemg signals correlated with the magnitude of the induced thermal change in the WT but not in the TRPA1-KO mice. The basal tearing was similar in the TRPA1-KO and WT mice. The electrophysiological data suggest that the TRPA1-dependent nerve activity, which declines with age, contributes to detecting the warming of the ocular surface and also to integrating the thermally-evoked reflex blink.

Background Electrical stimulation of skin afferents can induce somatosensory plasticity in humans. Nevertheless, it is unknown if this is possible to do through percutaneous stimulation of a peripheral nerve, which will allow for regional anaesthesia interventions. Furthermore, potentiation protocols applied over mainly non‐nociceptive fibres inhibit nociception in rodents, but this has not been tested in humans. Objective To determine whether a protocol aiming to depress the nociceptive circuit and another aiming to potentiate non‐nociceptive circuits produce regional hypoalgesia and changes in motor function, applied through percutaneous peripheral nerve stimulation (pPNS), and to assess which of them is more promising for pain relief, immediately and 24 h after the intervention. Methods PT‐cLF protocol aims to depress the nociceptive pathway through P ain T hreshold, c ontinuous L ow F requency stimulation and ST‐bHF aims to produce potentiation of the non‐nociceptive pathway, through S ensory T hreshold b urst stimulation at H igh F requency. All subjects ( n = 29) went through both protocols and a control condition in a randomized and blinded crossover design. Results Compared to control, ST‐bHF induced distal hypoalgesia, towards electrical ( p = 0.04) and mechanical stimuli ( p = 0.02) and produced mechanical hypoesthesia ( p = 0.02). Contrarily, hypoalgesia was not observed after PT‐cLF ( p > 0.05) but increased electrical motor threshold ( p = 0.04), reduced motor recruitment ( p = 0.03), and the subjects reported feeling reduced strength ( p < 0.01). Conclusion This works provides evidence that is possible to induce antinociceptive plasticity in a wide territory using pPNS. Moreover, it demonstrates for the first time in humans that a protocol aiming to produce long‐term potentiation applied predominantly over non‐nociceptive afferents induces hypoesthesia and hypoalgesia.