Naslov
Involvement of TRPV1-expressing primary afferents in botulinum toxin type A antinociceptive efficacy

Autori
Matak, Ivica ; Helyes, Zsuzsanna ; Lacković, Zdravko

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Special Issue: Abstracts of the 17th World Congress of Basic and Clinical Pharmacology, 13–18 July 2014, Cape Town, South Africa. Basic and Clinical Pharmacology & Toxicology. 115 (S1):201 / - : John Wiley & Sons, 2014, 201-201

Skup
17th World Congress of Basic and Clinical Pharmacology, 13–18 July 2014, Cape Town, South Africa

Mjesto i datum
Cape Town, Južnoafrička Republika, 13.07.2014. - 18.07.2014

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
botulinum toxin type A; pain; TRPV1-expressing neurons; gene knockouts

Sažetak
Botulinum toxin type A (BoNT/A) is suggested to be effective in chronic pain and migraine, however, with variable efficacy regarding different clinical conditions and variable response between individuals. We hypothesised that the mechanism of BoNT/A action and efficacy in pain reduction might be associated with capsaicin-sensitive neurons. To target capsaicin-sensitive primary afferents, rat trigeminal sensory ganglion was desensitized with high-dose intraganglionic capsaicin (2%). Effect of BoNT/A (peripheral facial injection) on orofacial formalin-induced pain was assessed in desensitized vs. vehicle-treated animals. In a mouse model of complete Freund's adjuvans (CFA)-induced hind paw-inflammation, antinociceptive effect of BoNT/A (s.c.) was examined in transient receptor potential vanilloid 1 (TRPV1) gene knockout animals. In addition, role of substance P and its postsynaptic receptor in BoNT/A's antinociceptive action was examined in tachykinin-1 and neurokinin-1 receptor gene knockout animals. BoNT/A antinociceptive activity in phase II hyperalgesic behavior in orofacial formalin test was prevented by capsaicin-induced desensitization of trigeminal afferents. In comparison to wild-type mice, BoNT/A preventive effect on CFA-induced mechanical allodynia was absent in animals deficient in neuronal elements related to capsaicin-sensitive afferents. Our results suggests that BoNT/A antinociceptive action is dependent on TRPV1-expressing (capsaicin-sensitive) neurons and its related presynaptic and postysnaptic elements. We hypothesise that BoNT/A might be more effective in pain disorders involving capsaicin-sensitive neurons, and predict that preserved function of TRPV1- expressing neurons might be necessary for positive response to BoNT/A treatment.

Izvorni jezik
Engleski

POVEZANOST RADA