Intradermal injection of Botulinum toxin type A alleviates infraorbital nerve constriction-induced thermal hyperalgesia in an operant assay.

Abstract

Recent studies have shown that infraorbital nerve constriction (IoNC)-induced mechanical allodynia has been attenuated by administration of highly purified 150-kDa Botulinum neurotoxin type A (BoNT/A). Here, we extend these studies to determine whether BoNT/A could attenuate IoNC-induced symptoms of thermal hyperalgesia. Instead of testing head withdrawal thresholds, a thermal operant assay was used to evaluate cortical processing of sensory input following IoNC. In this assay, a fasted rat's desire to obtain a food reward (sweetened condensed milk) is coupled to its ability to tolerate facial contact with a warm (45 °C) thermode. Bilateral IoNC decreased the ratio of thermode contact duration/event, which is an indicative of thermal hyperalgesia. BoNT/A injection intradermally in the area of infraorbital nerve (IoN) innervation 7 days after IoNC resulted in decreased number of facial contacts and increased the ratio of contact duration/event (measured at 14 days after IoNC). The BoNT/A (2-200 pg) effects were dose dependent and statistically significant at 100 and 200 pg (P < 0·05). Complete reversal of thermal hyperalgesia symptoms was obtained with a 200-pg dose, without affecting sham rat behaviour. Off-site (neck) injection of BoNT/A did not relieve thermal hyperalgesia, while co-injection of BoNT/A with a neutralising antibody in the area of IoN innervation prevented relief of thermal hyperalgesia. Neither IoNC nor BoNT/A injection affected operant assay parameters with a 24 °C thermode, indicating selectivity of thermal hyperalgesia measurements. These results strongly suggest that intradermal injection of BoNT/A in the area of IoN innervation alleviates IoNC-induced thermal hyperalgesia in an operant assay.

• Authors: A Kumada, Y Matsuka, I Spigelman, K Maruhama, Y Yamamoto, J K Neubert, T A Nolan, K Watanabe, K Maekawa, H Kamioka, T Yamashiro, T Kuboki, K Oguma
• Journal: Journal of oral rehabilitation (J Oral Rehabil) Vol. 39 Issue 1 Pg. 63-72 (Jan 2012) ISSN: 1365-2842 [Electronic] England
• PMID: 21793870 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 Blackwell Publishing Ltd.

Chemical References

• Botulinum Antitoxin
• Neurotoxins
• Botulinum Toxins, Type A

Topics

• Animals
• Botulinum Antitoxin (administration & dosage)
• Botulinum Toxins, Type A (administration & dosage)
• Case-Control Studies
• Constriction, Pathologic (complications)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Face
• Hot Temperature (adverse effects)
• Hyperalgesia (drug therapy, etiology)
• Injections, Intradermal
• Male
• Neurotoxins (administration & dosage)
• Orbit (innervation)
• Pain Threshold (drug effects)
• Rats
• Rats, Sprague-Dawley
• Treatment Outcome