Antinociceptive action of botulinum toxin type A in carrageenan-induced mirror pain

Drinovac Vlah, Višnja and Bach-Rojecky, Lidija and Lacković, Zdravko (2016) Antinociceptive action of botulinum toxin type A in carrageenan-induced mirror pain. Journal of Neural Transmission, 123 (12). pp. 1403-1413. ISSN 0300-9564

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Official URL: https://doi.org/10.1007/s00702-016-1605-7

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 GABAA antagonist 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.

Item Type:

Article

MeSH:

Analgesics / pharmacology ; Analgesics / therapeutic use ; Animals ; Bicuculline / therapeutic use ; Botulinum Toxins, Type A / pharmacology ; Botulinum Toxins, Type A / therapeutic use ; Calcitonin Gene-Related Peptide / metabolism ; Capsaicin / toxicity ; Carrageenan / toxicity ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drug Administration Routes ; Functional Laterality / drug effects ; Hyperalgesia / drug therapy ; Hyperalgesia / physiopathology ; Male ; Naloxone / analogs & derivatives ; Naloxone / therapeutic use ; Pain / chemically induced ; Pain / drug therapy ; Pain / pathology ; Pain Measurement ; Rats ; Rats, Wistar ; Spinal Cord / drug effects ; Spinal Cord / metabolism ; Synaptosomal-Associated Protein 25 / metabolism

Departments:

Katedra za farmakologiju

Depositing User:

Martina Žužak

Status:

Published

Creators: