{
  "abstract": "The neutralization of interleukin-16 (IL-16) or of its main target, CD4 receptors, as well as the reduction of its synthesis by inhibiting caspase-3 have been recently considered as possible strategies to inhibit pain. Here we study the involvement of peripheral mechanisms related to the IL-16/CD4 axis in the nociceptive responses evoked after ligation of sciatic nerve in mice. Systemic administration of anti-IL-16 or anti-CD4 antibodies inhibited hyperalgesia and allodynia measured 2 days after ligation in male and female mice. In addition, both antibodies were also analgesic 9 days after nerve ligation, supporting the participation of IL-16 and CD4 in the establishment and maintenance of neuropathic pain. Following nerve injury, Il16 expression remained unaltered in dorsal root ganglia (DRGs) and damaged nerves, whereas Casp3 expression increased in DRGs and the enzymatic activity of caspase-3 was enhanced in damaged nerves. Immunofluorescence assays demonstrated a limited presence of IL-16 in DRG neurons, that remained unmodified after injury, and a clear up-regulation of this cytokine in injured nerves. Double immunofluorescence assays with βIII-tubulin and S100β antibodies demonstrated that IL-16 is expressed both in axons and Schwann cells after nerve ligation. The ability of IL-16 to evoke nociception by directly acting on nerves was confirmed by intra-sciatic administration. Immunofluorescence labelling of CD4 receptors was also present in injured nerves, being also up-regulated both in axons and Schwann cells. Finally, hyperalgesia and allodynia were prevented by the intra-sciatic administration of anti-IL-16 or anti-CD4 antibodies, thus supporting the relevance of the IL-16/CD4 axis in neuropathic hypernociception.",
  "abstract_shown": true,
  "affiliations": [
    "Farmacología, Facultad de Medicina, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, C/Julián Clavería 6, Oviedo, Asturias, 33006, Spain.",
    "Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain.",
    "Departamento de Radiología, Complejo Asistencial Universitario de León, León, Spain.",
    "Farmacología, Facultad de Medicina, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, C/Julián Clavería 6, Oviedo, Asturias, 33006, Spain. luismen@uniovi.es.",
    "Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain. luismen@uniovi.es."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Alba Coro-Martín"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Alejandro Álvarez-Artime"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Sara González-Rodríguez"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "María González-Amor"
    },
    {
      "affs": [
        2
      ],
      "name": "David Corral-Fontecha"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ana Baamonde"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Luis Menéndez"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/647fn50jq8qk1.bib",
  "cited_by": 0,
  "doi": "10.1007/s12035-026-06280-2",
  "fulltext_url": "https://europepmc.org/articles/PMC13690839",
  "id": "647fn50jq8qk1",
  "issns": [
    "0893-7648",
    "1559-1182"
  ],
  "landing_url": "https://europepmc.org/article/MED/42911322",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2737|Pain Mechanisms and Treatments"
    ]
  ],
  "openalex": "W7223178405",
  "pdf_url": "https://europepmc.org/articles/PMC13690839?pdf=render",
  "pmcid": "PMC13690839",
  "pmid": "42911322",
  "published": "2026-10-22",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/647fn50jq8qk1.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:10Z",
      "native_id": "MED:42911322",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42911322"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Pain Mechanisms and Treatments",
      "subfield": "physiology"
    }
  ],
  "title": "Neural Expression of IL-16 Mediates Neuropathic Pain after Sciatic Injury in Mice.",
  "title_text": "Neural Expression of IL-16 Mediates Neuropathic Pain after Sciatic Injury in Mice.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:10Z",
  "url": "https://research.draconitic.com/paper/647fn50jq8qk1",
  "venue": "Molecular neurobiology",
  "versions": []
}