title: 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.
authors.affiliation: Department of Dental Anesthesiology and Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
authors.forename: Won-Ho
authors.initials: WH
authors.lastname: Lee
authors.forename: Teo Jeon
authors.initials: TJ
authors.lastname: Shin
authors.forename: Hyun Jeong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jin-Koo
authors.initials: JK
authors.lastname: Lee
authors.forename: Hong-Won
authors.initials: HW
authors.lastname: Suh
authors.forename: Sang Chul
authors.initials: SC
authors.lastname: Lee
authors.forename: Kyle
authors.initials: K
authors.lastname: Seo
mesh_terms: D000818:Animals; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010146:Pain / Q000378:metabolism / Q000517:prevention & control*; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods
chemical_list: D019274:Botulinum Toxins, Type A