{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:37:12Z","timestamp":1792809432252,"version":"4.5.0"},"reference-count":25,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVE<\/jats:title>\n                    <jats:p>Early repair of transected peripheral nerves is advocated to maximize recovery; however, clinical delays are common. Conditioning, a well-known method accelerating nerve regeneration, has never been used in a postinjury setting. The authors tested whether postinjury, prerepair conditioning electrical stimulation (CES) can biologically bridge the interval to surgery so that a delayed repair (DR) yields outcomes comparable to, or greater than, an immediate repair (IR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Adult male Sprague Dawley rats were randomized to 4 cohorts: 1) CES-cut-IR (CES 1 week before nerve cut + IR), 2) cut-IR (cut and IR, no CES), 3) cut-DR (cut, DR 10 days later, no CES), and 4) cut-CES-DR (nerve cut, CES on postinjury day 3, DR 7 days later). Outcomes evaluated included axon extension 14 days postrepair, sensory recovery (von Frey thresholds, intraepidermal nerve fiber density), and motor recovery (toe-spread and ladder-rung performance, compound muscle action potential [CMAP] amplitudes, gastrocnemius mass, and innervated neuromuscular junctions [NMJs]).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>For all outcomes evaluated, postinjury CES significantly improved regeneration and reinnervation when compared with no-CES controls. Furthermore, this cohort also had outcomes comparable to the IR cohort that had been treated with CES. Axon extension was comparable between the cut-CES-DR (12.5 \u00b1 0.9 mm) and the CES-cut-IR positive-control cohort (12.1 \u00b1 0.7 mm), and significantly longer than cut-IR (6.9 \u00b1 0.6 mm, p &lt; 0.001) and cut-DR (7.2 \u00b1 0.5 mm, p &lt; 0.001) controls. Between 7 and 8 weeks postrepair, sensory recovery assessed with von Frey filaments identified sensory recovery in the cut-CES-DR cohort comparable to the CES-cut-IR positive control, and significantly greater than the cut-IR and cut-DR controls (both p &lt; 0.001); these results were confirmed on intraepidermal nerve fiber density counts. At 8 weeks, motor function was improved in the cut-CES-DR cohort (toe spread 73.2% contralateral; ladder score 5.0 \u00b1 0.1) versus cut-IR and cut-DR cohorts (approximately 43%; scores 3.6 and 3.3, respectively; p &lt; 0.001), approximating CES-cut-IR cohort. This was confirmed by CMAP amplitudes, gastrocnemius muscle mass, and quantification of innervation NMJs, which demonstrated similar trends.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>A single, brief CES session delivered after injury and before repair enables delayed neurorrhaphy to recapitulate IR biology, significantly improving regeneration and reinnervation over delayed or IR without CES. This is the first demonstration of a conditioning-like effect in the clinically relevant situation of an already transected nerve. These results position postinjury CES as a practical bridge to surgery for timing-constrained nerve repairs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3171\/2026.3.jns252571","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:01:15Z","timestamp":1786492875000},"page":"1-11","source":"Crossref","is-referenced-by-count":0,"title":["Conditioning electrical stimulation after nerve injury: a clinically feasible strategy to enhance peripheral nerve regeneration"],"prefix":"10.3171","author":[{"given":"Christine A.","family":"Webber","sequence":"first","affiliation":[{"name":"Division of Anatomy, Department of Surgery, University of Alberta, Edmonton;"},{"name":"Neuroscience and Mental Health Institute, University of Alberta, Edmonton;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karyne N.","family":"Rabey","sequence":"additional","affiliation":[{"name":"Division of Anatomy, Department of Surgery, University of Alberta, Edmonton;"},{"name":"Neuroscience and Mental Health Institute, University of Alberta, Edmonton;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. Ming","family":"Chan","sequence":"additional","affiliation":[{"name":"Neuroscience and Mental Health Institute, University of Alberta, Edmonton;"},{"name":"Division of Physical Medicine and Rehabilitation, University of Alberta, Edmonton; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna-Lynn","family":"Senger","sequence":"additional","affiliation":[{"name":"Division of Plastic & Reconstructive Surgery, University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"issue":"7","key":"b1","series-title":"J Neurosci","first-page":"2602","article-title":"Brief electrical stimulation promotes the speed and accuracy of motor axonal regeneration","volume":"20","author":"Al-Majed AA","year":"2000","unstructured":"Al-Majed AA, Neumann CM, Brushart TM, Gordon T. Brief electrical stimulation promotes the speed and accuracy of motor axonal regeneration. J Neurosci. 2000;20(7):2602\u20132608. doi:10.1523\/JNEUROSCI.20-07-02602.2000"},{"issue":"15","key":"b2","series-title":"J Neurosci","first-page":"6631","article-title":"Electrical stimulation promotes motoneuron regeneration without increasing its speed or conditioning the neuron","volume":"22","author":"Brushart TM","year":"2002","unstructured":"Brushart TM, Hoffman PN, Royall RM, Murinson BB, Witzel C, Gordon T. Electrical stimulation promotes motoneuron regeneration without increasing its speed or conditioning the neuron. J Neurosci. 2002;22(15):6631\u20136638. doi:10.1523\/JNEUROSCI.22-15-06631.2002"},{"key":"b3","series-title":"Exp Neurol","first-page":"113147","article-title":"Conditioning electrical stimulation is superior to postoperative electrical stimulation, resulting in enhanced nerve regeneration and functional recovery","volume":"325","author":"Senger JB","year":"2020","unstructured":"Senger JB, Chan KM, Webber CA. Conditioning electrical stimulation is superior to postoperative electrical stimulation, resulting in enhanced nerve regeneration and functional recovery. Exp Neurol. 2020;325:113147. doi:10.1016\/j.expneurol.2019.113147"},{"issue":"6","key":"b4","series-title":"Muscle Nerve","first-page":"1151","article-title":"The use of electrical stimulation to enhance recovery following peripheral nerve injury","volume":"70","author":"Hardy PB","year":"2024","unstructured":"Hardy PB, Wang BY, Chan KM, Webber CA, Senger JB. The use of electrical stimulation to enhance recovery following peripheral nerve injury. Muscle Nerve. 2024;70(6):1151\u20131162. doi:10.1002\/mus.28262"},{"issue":"1","key":"b5","series-title":"Muscle Nerve","first-page":"15","article-title":"Investigating the mechanism of conditioning versus postoperative electrical stimulation to enhance nerve regeneration: one therapy, two distinct effects","volume":"72","author":"Hardy PB","year":"2025","unstructured":"Hardy PB, Wang BY, Chan KM, Webber CA, Senger JB. Investigating the mechanism of conditioning versus postoperative electrical stimulation to enhance nerve regeneration: one therapy, two distinct effects. Muscle Nerve. 2025;72(1):15\u201333. doi:10.1002\/mus.28385"},{"issue":"5","key":"b6","series-title":"J Neurosurg","first-page":"1442","article-title":"Recovering the regenerative potential in chronically injured nerves by using conditioning electrical stimulation","volume":"136","author":"Senger JLB","year":"2022","unstructured":"Senger JLB, Rabey KN, Acton L,  Recovering the regenerative potential in chronically injured nerves by using conditioning electrical stimulation. J Neurosurg. 2022;136(5):1442\u20131454. doi:10.3171\/2021.4.JNS21398"},{"key":"b7","series-title":"Exp Neurol","first-page":"60","article-title":"Conditioning electrical stimulation promotes functional nerve regeneration","volume":"315","author":"Senger JL","year":"2019","unstructured":"Senger JL, Chan KM, Macandili H,  Conditioning electrical stimulation promotes functional nerve regeneration. Exp Neurol. 2019;315:60\u201371. doi:10.1016\/j.expneurol.2019.02.001"},{"key":"b8","series-title":"Exp Neurol","first-page":"75","article-title":"Electrical stimulation as a conditioning strategy for promoting and accelerating peripheral nerve regeneration","volume":"302","author":"Senger JLB","year":"2018","unstructured":"Senger JLB, Verge VMK, Macandili HSJ, Olson JL, Chan KM, Webber CA. Electrical stimulation as a conditioning strategy for promoting and accelerating peripheral nerve regeneration. Exp Neurol. 2018;302:75\u201384. doi:10.1016\/j.expneurol.2017.12.013"},{"issue":"4","key":"b9","series-title":"Neurorehabil Neural Repair","first-page":"299","article-title":"Conditioning electrical stimulation is superior to postoperative electrical stimulation in enhanced regeneration and functional recovery following nerve graft repair","volume":"34","author":"Senger JLB","year":"2020","unstructured":"Senger JLB, Chan AWM, Chan KM,  Conditioning electrical stimulation is superior to postoperative electrical stimulation in enhanced regeneration and functional recovery following nerve graft repair. Neurorehabil Neural Repair. 2020;34(4):299\u2013308. doi:10.1177\/1545968320905801"},{"issue":"2","key":"b10","series-title":"Ann Neurol","first-page":"363","article-title":"Conditioning electrical stimulation accelerates regeneration in nerve transfers","volume":"88","author":"Senger JL","year":"2020","unstructured":"Senger JL, Rabey KN, Morhart MJ, Chan KM, Webber CA. Conditioning electrical stimulation accelerates regeneration in nerve transfers. Ann Neurol. 2020;88(2):363\u2013374. doi:10.1002\/ana.25796"},{"issue":"4","key":"b11","series-title":"Ann Neurol","first-page":"691","article-title":"The nerve conditioning lesion: a strategy to enhance nerve regeneration","volume":"83","author":"Senger JB","year":"2018","unstructured":"Senger JB, Verge VMK, Chan KM, Webber CA. The nerve conditioning lesion: a strategy to enhance nerve regeneration. Ann Neurol. 2018;83(4):691\u2013702. doi:10.1002\/ana.25209"},{"issue":"28","key":"b12","series-title":"J Vis Exp","first-page":"1204","article-title":"The ladder rung walking task: a scoring system and its practical application","volume":"2009","author":"Metz GA","unstructured":"Metz GA, Whishaw IQ. The ladder rung walking task: a scoring system and its practical application. J Vis Exp. 2009(28):1204. doi:10.3791\/1204"},{"key":"b13","article-title":"Conditioning electrical stimulation to improve outcomes in cubital tunnel syndrome","unstructured":"Conditioning electrical stimulation to improve outcomes in cubital tunnel syndrome. NCT05395715. ClinicalTrials.gov. Accessed May 28, 2026. https:\/\/clinicaltrials.gov\/study\/NCT05395715"},{"key":"b14","article-title":"Conditioning electrical stimulation to improve outcomes in carpal tunnel syndrome","unstructured":"Conditioning electrical stimulation to improve outcomes in carpal tunnel syndrome. NCT04191538. ClinicalTrials.gov. Accessed May 28, 2026. https:\/\/clinicaltrials.gov\/study\/NCT04191538"},{"key":"b15","article-title":"Conditioning electrical stimulation to improve outcomes in carpal tunnel syndrome","unstructured":"Conditioning electrical stimulation to improve outcomes in carpal tunnel syndrome. NCT04191538. ClinicalTrials.gov. Accessed May 28, 2026. https:\/\/clinicaltrials.gov\/study\/NCT04191538"},{"issue":"1","key":"b16","series-title":"Exp Neurol","first-page":"192","article-title":"Brief post-surgical electrical stimulation accelerates axon regeneration and muscle reinnervation without affecting the functional measures in carpal tunnel syndrome patients","volume":"223","author":"Gordon T","year":"2010","unstructured":"Gordon T, Amirjani N, Edwards DC, Chan KM. Brief post-surgical electrical stimulation accelerates axon regeneration and muscle reinnervation without affecting the functional measures in carpal tunnel syndrome patients. Exp Neurol. 2010;223(1):192\u2013202. doi:10.1016\/j.expneurol.2009.09.020"},{"issue":"6","key":"b17","series-title":"Ann Neurol","first-page":"996","article-title":"Electrical stimulation enhances sensory recovery: a randomized controlled trial","volume":"77","author":"Wong JN","year":"2015","unstructured":"Wong JN, Olson JL, Morhart MJ, Chan KM. Electrical stimulation enhances sensory recovery: a randomized controlled trial. Ann Neurol. 2015;77(6):996\u20131006. doi:10.1002\/ana.24397"},{"issue":"6","key":"b18","series-title":"Neurosurgery","first-page":"769","article-title":"Postsurgical electrical stimulation enhances recovery following surgery for severe cubital tunnel syndrome: a double-blind randomized controlled trial","volume":"86","author":"Power HA","year":"2020","unstructured":"Power HA, Morhart MJ, Olson JL, Chan KM. Postsurgical electrical stimulation enhances recovery following surgery for severe cubital tunnel syndrome: a double-blind randomized controlled trial. Neurosurgery. 2020;86(6):769\u2013777. doi:10.1093\/neuros\/nyz322"},{"issue":"5","key":"b19","series-title":"Plast Reconstr Surg Glob Open","first-page":"e3570","article-title":"Chronic nerve injuries and delays in surgical treatment negatively impact patient-reported quality of life","volume":"9","author":"Felder JM","year":"2021","unstructured":"Felder JM, Ducic I. Chronic nerve injuries and delays in surgical treatment negatively impact patient-reported quality of life. Plast Reconstr Surg Glob Open. 2021;9(5):e3570. doi:10.1097\/GOX.0000000000003570"},{"issue":"6","key":"b20","series-title":"J Hand Surg Glob Online","first-page":"801","article-title":"Case series of traumatic peripheral nerve injuries in pediatric patients treated with allograft repair","volume":"6","author":"Van Gheem J","year":"2024","unstructured":"Van Gheem J, Rounds A, Blackwood T,  Case series of traumatic peripheral nerve injuries in pediatric patients treated with allograft repair. J Hand Surg Glob Online. 2024;6(6):801\u2013807. doi:10.1016\/j.jhsg.2024.05.008"},{"issue":"5 Pt 2","key":"b21","series-title":"J Neurosci","first-page":"3886","article-title":"Contributing factors to poor functional recovery after delayed nerve repair: prolonged denervation","volume":"15","author":"Fu SY","year":"1995","unstructured":"Fu SY, Gordon T. Contributing factors to poor functional recovery after delayed nerve repair: prolonged denervation. J Neurosci. 1995;15(5 Pt 2):3886\u20133895. doi:10.1523\/JNEUROSCI.15-05-03886.1995"},{"issue":"14","key":"b22","series-title":"J Neurosci","first-page":"5325","article-title":"The basis for diminished functional recovery after delayed peripheral nerve repair","volume":"31","author":"Gordon T","year":"2011","unstructured":"Gordon T, Tyreman N, Raji MA. The basis for diminished functional recovery after delayed peripheral nerve repair. J Neurosci. 2011;31(14):5325\u20135334. doi:10.1523\/JNEUROSCI.6156-10.2011"},{"issue":"3","key":"b23","series-title":"Ann Plast Surg","first-page":"e1","article-title":"Evidence-based approach to timing of nerve surgery: a review","volume":"87","author":"MacKay BJ","year":"2021","unstructured":"MacKay BJ, Cox CT, Valerio IL,  Evidence-based approach to timing of nerve surgery: a review. Ann Plast Surg. 2021;87(3):e1\u2013e21. doi:10.1097\/SAP.0000000000002767"},{"issue":"2","key":"b24","series-title":"Exp Neurol","first-page":"347","article-title":"Electrical stimulation promotes sensory neuron regeneration and growth-associated gene expression","volume":"205","author":"Geremia NM","year":"2007","unstructured":"Geremia NM, Gordon T, Brushart TM, Al-Majed AA, Verge VM. Electrical stimulation promotes sensory neuron regeneration and growth-associated gene expression. Exp Neurol. 2007;205(2):347\u2013359. doi:10.1016\/j.expneurol.2007.01.040"},{"issue":"3","key":"b25","series-title":"Cell Mol Neurobiol","first-page":"379","article-title":"Electrical stimulation accelerates and enhances expression of regeneration-associated genes in regenerating rat femoral motoneurons","volume":"24","author":"Al-Majed AA","year":"2004","unstructured":"Al-Majed AA, Tam SL, Gordon T. Electrical stimulation accelerates and enhances expression of regeneration-associated genes in regenerating rat femoral motoneurons. Cell Mol Neurobiol. 2004;24(3):379\u2013402. doi:10.1023\/b:cemn.0000022770.66463.f7"}],"container-title":["Journal of Neurosurgery"],"original-title":[],"link":[{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/aop\/article-10.3171-2026.3.JNS252571\/article-10.3171-2026.3.JNS252571.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/aop\/article-10.3171-2026.3.JNS252571\/article-10.3171-2026.3.JNS252571.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:42:44Z","timestamp":1792806164000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/aop\/article-10.3171-2026.3.JNS252571\/article-10.3171-2026.3.JNS252571.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,1]]},"references-count":25,"URL":"https:\/\/doi.org\/10.3171\/2026.3.jns252571","relation":{},"ISSN":["0022-3085","1933-0693"],"issn-type":[{"value":"0022-3085","type":"print"},{"value":"1933-0693","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,1]]}}}