Involvement of μ-opioid receptors in antinociceptive action of botulinum toxin type A

Scientific paper - Original scientific paper

• Author: Višnja Drinovac
• Author: Lidija Bach-Rojecky
• Author: Ivica Matak
• Author: Zdravko Lacković
• Author's institution: University of Zagreb; School of Medicine
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences

Abstract (english)

Botulinum toxin A (BTX-A) is approved for treatment of chronic migraine and has been investigated in various other painful conditions. Recent evidence demonstrated retrograde axonal transport and suggested the involvement of CNS in antinociceptive effect of BTX-A. However, the mechanism of BTX-A central antinociceptive action is unknown. In this study we investigated the potential role of opioid receptors in BTX-A's antinociceptive activity. In formalin-induced inflammatory pain we assessed the effect of opioid antagonists on antinociceptive activity of BTX-A. Naltrexone was injected subcutaneously (0.02-2 mg/kg) or intrathecally (0.07 μg/10 μl-350 μg/10 μl), while selective μ-antagonist naloxonazine was administered intraperitoneally (5 mg/kg) prior to nociceptive testing. The influence of naltrexone (2 mg/kg s.c.) on BTX-A antinociceptive activity was examined additionally in an experimental neuropathy induced by partial sciatic nerve transection. To investigate the effects of naltrexone and BTX-A on neuronal activation in spinal cord, c-Fos expression was immunohistochemically examined in a model of formalin-induced pain. Antinociceptive effects of BTX-A in formalin and sciatic nerve transection-induced pain were prevented by non-selective opioid antagonist naltrexone. Similarly, BTX-A-induced pain reduction was abolished by low dose of intrathecal naltrexone and by selective μ-antagonist naloxonazine. BTX-A-induced decrease in dorsal horn c-Fos expression was prevented by naltrexone. Prevention of BTX-A effects on pain and c-Fos expression by opioid antagonists suggest that the central antinociceptive action of BTX-A might be associated with the activity of endogenous opioid system (involving μ-opioid receptor). These results provide first insights into the mechanism of BTX-A's central antinociceptive activity.

• Keywords (english): Analgesics/antagonists & inhibitors; Analgesics/pharmacology; Animals; Botulinum Toxins, Type A/antagonists & inhibitors; Botulinum Toxins, Type A/pharmacology; Dose-Response Relationship, Drug; Drug Interactions; Male; Naloxone/analogs & derivatives; Naloxone/pharmacology; Naltrexone/pharmacology; Narcotic Antagonists/pharmacology; Posterior Horn Cells/drug effects; Posterior Horn Cells/metabolism; Proto-Oncogene Proteins c-fos/metabolism; Rats; Receptors, Opioid, mu/agonists; Receptors, Opioid, mu/antagonists & inhibitors
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Accepted version
• Journal title: Neuropharmacology
• Numbering: vol. 70, pp. 331-337
• p-ISSN: 0028-3908
• DOI: https://doi.org/10.1016/j.neuropharm.2013.02.011
• URN:NBN: urn:nbn:hr:105:971290
• Publication: 2013-07
• Document URL: https://doi.org/10.1016/j.neuropharm.2013.02.011
• Type of resource: Text
• Access conditions: Open access
• Created on: 2024-03-27 19:59:34