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Effects of intraplantar botulinum toxin‐B on carrageenan‐induced changes in nociception and spinal phosphorylation of GluA1 and Akt
Author(s) -
Sikandar Shafaq,
Gustavsson Ynette,
Marino Marc J.,
Dickenson Anthony H.,
Yaksh Tony L.,
Sorkin Linda S.,
Ramachandran Roshni
Publication year - 2016
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.13261
Subject(s) - nociception , pharmacology , glutamate receptor , nmda receptor , chemistry , allodynia , phosphorylation , hyperalgesia , medicine , receptor , biochemistry
Increasing evidence suggests that botulinum neurotoxins (Bo NT s) delivered into the skin and muscle in certain human and animal pain states may exert antinociceptive efficacy though their uptake and transport to central afferent terminals. Cleavage of soluble N‐methylaleimide‐sensitive attachment protein receptor by Bo NT s can impede vesicular mediated neurotransmitter release as well as transport/insertion of channel/receptor subunits into plasma membranes, an effect that can reduce activity‐evoked facilitation. Here, we explored the effects of intraplantar botulinum toxin‐ B (BoNT‐B) on peripheral inflammation and spinal nociceptive processing in an inflammatory model of pain. C57 BL /6 mice (male) received unilateral intraplantar Bo NT (1 U, 30 μL) or saline prior to intraplantar carrageenan (20 μL, 2%) or intrathecal N‐methyl‐D‐aspartate ( NMDA ), substance P or saline (5 μL). Intraplantar carrageenan resulted in edema and mechanical allodynia in the injected paw and increased phosphorylation of a glutamate subunit ( pG luA1ser845) and a serine/threonine‐specific protein kinase ( pA ktser473) in spinal dorsal horn along with an increased incidence of spinal c‐Fos positive cells. Pre‐treatment with intraplantar Bo NT ‐B reduced carrageenan evoked: (i) allodynia, but not edema; (ii) pG luA1 and pA kt and (iii) c‐Fos expression. Further, intrathecal NMDA and substance P each increased dorsal horn levels of pG luA1 and pA kt. Intraplantar Bo NT ‐B inhibited NMDA , but not substance P evoked phosphorylation of GluA1 and Akt. These results suggest that intraplantar toxin is transported centrally to block spinal activation and prevent phosphorylation of a glutamate receptor subunit and a kinase, which otherwise contribute to facilitated states.