Botulinum neurotoxin type A counteracts neuropathic pain and facilitates functional recovery after peripheral nerve injury in animal models.
A growing interest was recently focused on the use of Botulinum neurotoxin serotype A (BoNT/A) for fighting pain. The aim of this study was to investigate the effects of BoNT/A on neuropathic pain. It was observed that BoNT/A is able to counteract neuropathic pain induced by chronic constriction injury (CCI) to the sciatic nerve both in mice and in rats. This effect is already present after a single intraplantar (i.pl.) or intrathecal (i.t.) neurotoxin administration that significantly reduces the sciatic nerve ligation-induced mechanical allodynia in mice and rats and thermal hyperalgesia in rats. This effect was evident starting 24 h after the administration of BoNT/A and it was long-lasting, being present 81 or 25 days after i.pl. injection of the higher dose in mice (15 pg/paw) and rats (75 pg/paw), respectively, and 35 days after i.t. injection in rats (75 pg/rat). Moreover, BoNT/A-injected mice showed a quicker recovery of the walking pattern and weight bearing compared to control groups. The behavioral improvement was accompanied by structural modifications, as revealed by the expression of cell division cycle 2 (Cdc2) and growth associated protein 43 (GAP-43) regeneration associated proteins, investigated by immunofluorescence and Western blotting in the sciatic nerve, and by the immunofluorescence expression of S100β and glial fibrillary acidic protein (GFAP) Schwann cells proteins. In conclusion, the present research demonstrate long-lasting anti-allodynic and anti-hyperalgesic effects of BoNT/A in animal models of neuropathic pain together with an acceleration of regenerative processes in the injured nerve, as evidenced by both behavioral and immunohistochemistry/blotting analysis. These results may have important implications in the therapy of neuropathic pain.
Marinelli
S
S
CNR, Institute of Neuroscience, Via del Fosso di Fiorano 64, 00143 Roma, Italy.
Luvisetto
S
S
Cobianchi
S
S
Makuch
W
W
Obara
I
I
Mezzaroma
E
E
Caruso
M
M
Straface
E
E
Przewlocka
B
B
Pavone
F
F
D000704:Analysis of Variance; D000818:Animals; D019274:Botulinum Toxins, Type A / Q000627:therapeutic use*; D016203:CDC2 Protein Kinase; D018797:Cell Cycle Proteins / Q000378:metabolism; D018844:Cyclin-Dependent Kinases; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019922:GAP-43 Protein / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D009414:Nerve Growth Factors / Q000378:metabolism; D009465:Neuromuscular Agents / Q000627:therapeutic use*; D017288:Pain Threshold / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects*; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism; D012585:Sciatica / Q000188:drug therapy* / Q000503:physiopathology; D018709:Statistics, Nonparametric; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism; D016474:Weight-Bearing
D018797:Cell Cycle Proteins; D019922:GAP-43 Protein; D005904:Glial Fibrillary Acidic Protein; D009414:Nerve Growth Factors; D009465:Neuromuscular Agents; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D050825:Synaptosomal-Associated Protein 25; D016203:CDC2 Protein Kinase; C548796:Cdk1 protein, rat; D018844:Cyclin-Dependent Kinases; D019274:Botulinum Toxins, Type A