Intrathecal administration of botulinum neurotoxin type A attenuates formalin-induced nociceptive responses in mice.

Abstract:

BACKGROUND:Botulinum neurotoxin type A (BoNT/A) has been used as an analgesic for myofascial pain syndromes, migraine, and other types of headaches. Although an antinociceptive effect of central or peripheral administration of BoNT/A is suggested, the effect at the spinal level is still unclear. In this study, we evaluated the antinociceptive effect of intrathecally administered BoNT/A on the ICR mice during the formalin test. METHODS:BoNT/A (0.01 U/mouse) was injected intrathecally in ICR mice, and we observed formalin-induced inflammatory pain behaviors at days 1, 4, 7, 10, 14, 21, and 28 after the injection. We also examined the level of calcitonin gene-related peptide (CGRP), phosphorylated extracellullar signal-regulated kinases (p-ERK), and phosphorylated Ca(2+)/calmodulin-dependent protein kinase type 2 (p-CaMK-II) using immunoblot or immunohistochemical analyses before and after BoNT/A intrathecal injection. RESULTS:Even a single intrathecal injection of BoNT/A significantly decreased the nociceptive responses in the first phase (10 and 14 days later) and in the second phase of the formalin test at 1, 4, 7, 10, and 14 days later (P < 0.05) without any locomotor changes. Interestingly, intrathecal BoNT/A attenuated the expression level of CGRP, p-ERK, and p-CaMK-II in the 4th and 5th lumbar spinal dorsal horn at 10 days after injection in comparison with control. CONCLUSIONS:We showed that intrathecally administered BoNT/A may have a central analgesic effect on inflammatory pain through the modulation of central sensitization. BoNT/A, with its long-lasting antinociceptive effect, may be a useful analgesic in inflammatory pain.

journal_name

Anesth Analg

journal_title

Anesthesia and analgesia

authors

Lee WH,Shin TJ,Kim HJ,Lee JK,Suh HW,Lee SC,Seo K

doi

10.1213/ANE.0b013e3181ffa1d7

subject

Has Abstract

pub_date

2011-01-01 00:00:00

pages

228-35

issue

1

eissn

0003-2999

issn

1526-7598

pii

ANE.0b013e3181ffa1d7

journal_volume

112

pub_type

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