Premium
Bilateral analgesic effects of abobotulinumtoxinA (Dysport ® ) following unilateral administration in the rat
Author(s) -
FavreGuilmard C.,
Chabrier P.E.,
Kalinichev M.
Publication year - 2017
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/ejp.995
Subject(s) - analgesic , administration (probate law) , anesthesia , medicine , pharmacology , political science , law
Background In addition to inhibition of muscle and glandular hyperactivity, botulinum neurotoxin (Bo NT ) type A also interferes with pain processing. Previously, in a rat model of paclitaxel‐induced polyneuropathy, abobotulinumtoxinA (aboBo NT ‐A) elicited analgesic effects not only in the injected paw, but also in the contralateral, non‐injected paw. Methods Here, we assessed bilateral analgesic effects of unilateral aboBo NT ‐A in several chronic pain models in Sprague‐Dawley rats. Effects of aboBo NT ‐A on the paw withdrawal threshold in response to mechanical pressure was assessed in models of streptozotocin‐induced diabetic polyneuropathy, chronic constriction injury ( CCI )‐associated mononeuropathy, and bilateral carrageenan‐induced inflammatory pain. Results In diabetic polyneuropathy, aboBo NT ‐A (15, 20 U/kg) reversed hyperalgesia in the toxin‐injected and non‐injected paws. In unilateral CCI ‐exposed animals, 20 U/kg aboBo NT ‐A given ipsilateral to the injury reversed mechanical hyperalgesia, while 30 U/kg aboBo NT ‐A given contralateral to the injury had no effect. In carrageenan‐induced bilateral inflammatory pain, aboBo NT ‐A (20, 30 U/kg) reversed hyperalgesia in both toxin‐injected and non‐injected paws. Discussion These results suggest that unilateral administration of aboBo NT ‐A results in bilateral reduction in mechanical hyperalgesia across neuropathic and inflammatory pain conditions, bilateral activation of sensory neurons being prerequisite for its expression. Future studies involving effects on other sensory modalities as well as those evaluating diffusion and migration of the toxin away from the injection site can shed light on mechanisms of this phenomenon. Significance The results expand evidence on bilateral analgesic effects of aboBo NT ‐A following unilateral administration across pain modalities, as the phenomenon is seen in more than one model of polyneuropathy as well as in a model of chronic inflammatory pain when the latter is rendered bilateral. The mechanism of bilateral analgesic effects of aboBo NT ‐A may require activation of the peripheral sensory neurons and involve retrograde axonal transport of the toxin into the spinal cord.