title: Antinociceptive action of botulinum toxin type A in carrageenan-induced mirror pain.
abstract: "Mirror pain" or mirror-image pain (MP) is pain opposite to the side of injury. Mechanism and frequency in humans are not known. There is no consent on therapy. Here we report that unilaterally injected botulinum toxin type A (BT-A) has bilateral effect in experimental MP, thus deserves to be investigated as therapy for this condition. We examined the localization of BT-A's bilateral antinociceptive action in MP induced by 3 % carrageenan intramuscular injection in Wistar rats. BT-A was applied peripherally (5 U/kg), into ipsilateral or contralateral hind paw pad (i.pl.) and centrally (1 U/kg), at spinal (intrathecally, i.t.) or supraspinal (intracisternally, i.c.) level. Additionally, we examined the involvement of central opioid and GABAergic systems, as well as the contribution of peripheral capsaicin-sensitive neurons to BT-A's bilateral antinociceptive effect. Ipsilateral i.pl. and i.t. BT-A reduced the bilateral mechanical sensitivity to von Frey filaments, while contralateral i.pl. and i.c. treatments had no effect on either tested side. Bilateral antinociceptive effect of ipsilateral i.pl. BT-A was prevented by μ-opioid antagonist naloxonazine (1.5 μg/10 μl) and GABAAantagonist bicuculline (1 μg/10 μl) if applied at the spinal level, in contrast to supraspinal application of the same doses. Local treatment of sciatic nerve with 2 % capsaicin 5 days following BT-A i.pl. injection caused desensitization of sciatic capsaicin-sensitive fibers, but did not affect bilateral antinociceptive effect of BT-A and the presence of cleaved SNAP-25 at the spinal cord slices. Present experiments suggest segmental actions of peripheral BT-A at spinal level, which are probably not solely dependent on capsaicin-sensitive neurons.
authors: Department of Pharmacology, University of Zagreb Faculty of Pharmacy and Biochemistry, Domagojeva 2, 10000, Zagreb, Croatia.
authors: V
authors: V
authors: Drinovac Vlah
authors: Department of Pharmacology, University of Zagreb Faculty of Pharmacy and Biochemistry, Domagojeva 2, 10000, Zagreb, Croatia. lbach@pharma.hr.
authors: L
authors: L
authors: Bach-Rojecky
authors: Laboratory of Molecular Neuropharmacology, Department of Pharmacology and Croatian Brain Research Institute, University of Zagreb School of Medicine, Šalata 11, 10000, Zagreb, Croatia.
authors: Z
authors: Z
authors: Lacković
mesh_terms: D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001640:Bicuculline / Q000627:therapeutic use; D019274:Botulinum Toxins, Type A / Q000494:pharmacology* / Q000627:therapeutic use*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin / Q000633:toxicity; D002351:Carrageenan / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D007839:Functional Laterality / Q000187:drug effects*; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D009270:Naloxone / Q000031:analogs & derivatives / Q000627:therapeutic use; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D010147:Pain Measurement; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism
chemical_list: D000700:Analgesics; D050825:Synaptosomal-Associated Protein 25; D009270:Naloxone; C034643:naloxonazine; D002351:Carrageenan; D019274:Botulinum Toxins, Type A; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D001640:Bicuculline
keywords: Botulinum toxin A; Capsaicin-sensitive neurons; Cleaved SNAP-25; GABAA antagonist; Mirror pain; μ-opioid antagonist