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Intradermal injection of Botulinum toxin type A alleviates infraorbital nerve constriction‐induced thermal hyperalgesia in an operant assay
Author(s) -
KUMADA A.,
MATSUKA Y.,
SPIGELMAN I.,
MARUHAMA K.,
YAMAMOTO Y.,
NEUBERT J. K.,
NOLAN T. A.,
WATANABE K.,
MAEKAWA K.,
KAMIOKA H.,
YAMASHIRO T.,
KUBOKI T.,
OGUMA K.
Publication year - 2012
Publication title -
journal of oral rehabilitation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.991
H-Index - 93
eISSN - 1365-2842
pISSN - 0305-182X
DOI - 10.1111/j.1365-2842.2011.02236.x
Subject(s) - infraorbital nerve , hyperalgesia , intradermal injection , anesthesia , chemistry , botulinum toxin , allodynia , nociception , medicine , pharmacology , receptor , immunology
Summary 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.