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Several efforts have been done to described changes in axotomized neurons, however, there is scarce data on changes occurring in intact neurons, despite experimental evidence of functional changes. To address this issue, we analysed by immunohistochemistry the presence of phosphorylated signal transducer and activator of transcription 3 (pSTAT3), an accepted marker of regeneration, within DRGs where axotomized neurons were retrogradely labelled following peripheral nerve injury. Likewise, we have characterized abnormal electrophysiological properties in intact fibres after partial nerve injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods\/Results<\/jats:title><jats:p>We showed that induction of pSTAT3 in sensory neurons was similar after partial or total transection of the sciatic nerve and to the same extent within axotomized and non\u2010axotomized neurons. We also examined pSTAT3 presence on non\u2010peptidergic and peptidergic nociceptors. Whereas the percentage of neurons marked by IB4 decrease after injury, the proportion of CGRP neurons did not change, but its expression switched from small\u2010 to large\u2010diameter neurons. Besides, the percentage of CGRP+ neurons expressing pSTAT3 increased significantly 2.5\u2010folds after axotomy, preferentially in neurons with large diameters. Electrophysiological recordings showed that after nerve damage, most of the neurons with ectopic spontaneous activity (39\/46) were non\u2010axotomized C\u2010fibres with functional receptive fields in the skin far beyond the site of damage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Neuronal regeneration after nerve injury, likely triggered from the site of injury, may explain the abnormal functional properties gained by intact neurons, reinforcing their role in neuropathic pain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Positive symptoms in patients with peripheral neuropathies correlate to abnormal functioning of different subpopulations of primary afferents. Peripheral nerve damage triggers regenerating programs in the cell bodies of axotomized but also in non\u2010axotomized nociceptors which is in turn, develop abnormal spontaneous and evoked discharges. Therefore, intact nociceptors have a significant role in the development of neuropathic pain due to their hyperexcitable peripheral terminals. Therapeutical targets should focus on inhibiting peripheral hyperexcitability in an attempt to limit peripheral and central sensitization.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ejp.1718","type":"journal-article","created":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T09:57:02Z","timestamp":1608544622000},"page":"886-901","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Activation of the regeneration\u2010associated gene STAT3 and functional changes in intact nociceptors after peripheral nerve damage in mice"],"prefix":"10.1002","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1558-9829","authenticated-orcid":false,"given":"Laura","family":"Bernal","sequence":"first","affiliation":[{"name":"Department of System\u2019s Biology Medical School University of Alcala Alcal\u00e1 de Henares 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