Botulinum toxin type A selectivity for certain types of pain is associated with capsaicin-sensitive neurons

Znanstveni rad - Izvorni znanstveni rad

• Autor: Ivica Matak
• Autor: Ornella Rossetto
• Autor: Zdravko Lacković
• Autorova ustanova: Sveučilište u Zagrebu; Medicinski fakultet
• Znanstveno / umjetničko područje, polje i grana: BIOMEDICINA I ZDRAVSTVO; Temeljne medicinske znanosti

Sažetak (engleski)

Unlike most classical analgesics, botulinum toxin type A (BoNT/A) does not alter acute nociceptive thresholds, and shows selectivity primarily for allodynic and hyperalgesic responses in certain pain conditions. We hypothesized that this phenomenon might be explained by characterizing the sensory neurons targeted by BoNT/A in the central nervous system after its axonal transport. BoNT/A's central antinociceptive activity following its application into the rat whisker pad was examined in trigeminal nucleus caudalis (TNC) and higher-level nociceptive brain areas using BoNT/A-cleaved synaptosomal-associated protein 25 (SNAP-25) and c-Fos immunohistochemistry. Occurrence of cleaved SNAP-25 in TNC was examined after nonselective ganglion ablation with formalin or selective denervation of capsaicin-sensitive (vanilloid receptor-1 or TRPV1-expressing) neurons, and in relation to different cellular and neuronal markers. Regional c-Fos activation and effect of TRPV1-expressing afferent denervation on toxin's antinociceptive action were studied in formalin-induced orofacial pain. BoNT/A-cleaved SNAP-25 was observed in TNC, but not in higher-level nociceptive nuclei. Cleaved SNAP-25 in TNC disappeared after formalin-induced trigeminal ganglion ablation or capsaicin-induced sensory denervation. Occurrence of cleaved SNAP-25 in TNC and BoNT/A antinociceptive activity in formalin-induced orofacial pain were prevented by denervation with capsaicin. Cleaved SNAP-25 localization demonstrated toxin's presynaptic activity in TRPV1-expressing neurons. BoNT/A reduced the c-Fos activation in TNC, locus coeruleus, and periaqueductal gray. Present experiments suggest that BoNT/A alters the nociceptive transmission at the central synapse of primary afferents. Targeting of TRPV1-expressing neurons might be associated with observed selectivity of BoNT/A action only in certain types of pain.

• Ključne riječi (engleski): Animals; Botulinum Toxins, Type A/pharmacology; Botulinum Toxins, Type A/therapeutic use; Capsaicin/pharmacology; Male; Pain/drug therapy; Pain/metabolism; Proto-Oncogene Proteins c-fos/metabolism; Rats; Rats, Wistar; Sensory Receptor Cells/drug effects; Sensory Receptor Cells/metabolism; Synaptosomal-Associated Protein 25/metabolism; TRPV Cation Channels/metabolism; Trigeminal Ganglion/drug effects; Trigeminal Ganglion/metabolism
• Jezik: engleski
• Vrsta publikacije: Znanstveni rad - Izvorni znanstveni rad
• Status objave: Objavljen
• Vrsta recenzije: Recenziran
• Verzija publikacije: Završna verzija rukopisa prihvaćena za objavljivanje (postprint)
• Naslov časopisa: Pain
• Brojčani podaci: vol. 155, br. 8, str. 1516-1526
• p-ISSN: 1872-6623
• DOI: https://doi.org/10.1016/j.pain.2014.04.027
• URN:NBN: urn:nbn:hr:105:970510
• Datum objave publikacije: 2014-08
• URL dokumenta: https://doi.org/10.1016/j.pain.2014.04.027
• Vrsta resursa: Tekst
• Prava pristupa: Otvoreni pristup
• Datum i vrijeme pohrane: 2024-03-28 08:08:12