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As PICs are highly sensitive to synaptic inhibition and facilitated by serotonin and noradrenaline, we hypothesised that both reciprocal inhibition (RI) induced by antagonist nerve stimulation and whole\u2010body relaxation (WBR) would reduce PICs in humans. To test this, we estimated PICs using the well\u2010established paired motor unit (MU) technique. High\u2010density surface electromyograms were recorded from gastrocnemius medialis during voluntary, isometric 20\u2010s ramp, plantarflexor contractions and decomposed into MU discharges to calculate delta frequency (\u0394\n                      <jats:italic>F<\/jats:italic>\n                      ). Moreover, another technique (VibStim), which evokes involuntary contractions proposed to result from PIC activation, was used. Plantarflexion torque and soleus activity were recorded during 33\u2010s Achilles tendon vibration and simultaneous 20\u2010Hz bouts of neuromuscular electrical stimulation (NMES) of triceps surae. \u0394\n                      <jats:italic>F<\/jats:italic>\n                      was decreased by RI (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a015, 5 females) and WBR (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a015, 7 females). In VibStim, torque during vibration at the end of NMES and sustained post\u2010vibration torque were reduced by WBR (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a019, 10 females), while other variables remained unchanged. All VibStim variables remained unaltered in RI (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a020, 10 females). Analysis of multiple human MUs in this study demonstrates the ability of local, focused inhibition to attenuate the effects of PICs on motoneuron output during voluntary motor control. Moreover, it shows the potential to reduce PICs through non\u2010pharmacological, neuromodulatory interventions such as WBR. The absence of a consistent effect in VibStim might be explained by a floor effect resulting from low\u2010magnitude involuntary torque combined with the negative effects of the interventions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Spinal motoneurons transmit signals to skeletal muscles to regulate their contraction. Motoneuron firing partly depends on their intrinsic properties such as the strength of persistent (long\u2010lasting) inward currents (PICs) that make motoneurons more responsive to excitatory input.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>In this study, we demonstrate that both reciprocal inhibition onto motoneurons and whole\u2010body relaxation reduce the contribution of PICs to human motoneuron firing. This was observed through analysis of the firing of single motor units during voluntary contractions.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>However, an alternative technique that involves tendon vibration and neuromuscular electrical stimulation to evoke involuntary contractions showed less effect. Thus, it remains unclear whether this alternative technique can be used to estimate PICs under all physiological conditions.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>These results improve our understanding of the mechanisms of PIC depression in human motoneurons. Potentially, non\u2010pharmacological interventions such as electrical stimulation or relaxation could attenuate unwanted PIC\u2010induced muscle contractions in conditions characterised by motoneuron hyperexcitability.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp282765","type":"journal-article","created":{"date-parts":[[2022,4,18]],"date-time":"2022-04-18T13:53:55Z","timestamp":1650290035000},"page":"2765-2787","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Effects of reciprocal inhibition and whole\u2010body relaxation on persistent inward currents estimated by two different methods"],"prefix":"10.1113","volume":"600","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0327-3253","authenticated-orcid":false,"given":"Ricardo N. O.","family":"Mesquita","sequence":"first","affiliation":[{"name":"Centre for Human Performance School of Medical and Health Sciences Edith Cowan University  Perth Australia"},{"name":"Neuroscience Research Australia  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8976-5162","authenticated-orcid":false,"given":"Janet L.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Centre for Human Performance School of Medical and Health Sciences Edith Cowan University  Perth Australia"},{"name":"Neuroscience Research Australia  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4667-4257","authenticated-orcid":false,"given":"Gabriel S.","family":"Trajano","sequence":"additional","affiliation":[{"name":"School of Exercise and Nutrition Sciences and Institute of Health and Biomedical Innovation Queensland University of Technology  Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0118-1216","authenticated-orcid":false,"given":"Jakob","family":"\u0160karabot","sequence":"additional","affiliation":[{"name":"School of Sport Exercise and Health Sciences Loughborough University  Leicestershire UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8338-5978","authenticated-orcid":false,"given":"Ale\u0161","family":"Holobar","sequence":"additional","affiliation":[{"name":"Faculty of Electrical Engineering and Computer Science University of Maribor  Maribor Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2757-2979","authenticated-orcid":false,"given":"Bas\u00edlio A. 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