ABSTRACT
The mechanism of botulinum toxin type A (BTX-A) antinociceptive action in the central nervous system is little known. The potential interaction between BTX-A and GABAergic system has not been investigated previously. In the present study, we demonstrate prevention of BTX-A antinociceptive effect on formalin-induced inflammatory pain and partial sciatic nerve transection-induced mechanical allodynia by GABA-A antagonist bicuculline, thus suggesting association of the GABA-A receptors and antinociceptive action of BTX-A.
Subject(s)
Botulinum Toxins, Type A/therapeutic use , Neurotoxins/therapeutic use , Pain/prevention & control , Receptors, GABA-A/metabolism , Sciatica/prevention & control , Animals , Bicuculline/pharmacology , Disease Models, Animal , Drug Administration Routes , Formaldehyde/toxicity , Hyperalgesia/drug therapy , Pain/chemically induced , Pain Measurement/drug effects , Proto-Oncogene Proteins c-fos/metabolism , Rats , Rats, WistarABSTRACT
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.
Subject(s)
Analgesics/pharmacology , Botulinum Toxins, Type A/pharmacology , Receptors, Opioid, mu/agonists , Receptors, Opioid, mu/antagonists & inhibitors , Analgesics/antagonists & inhibitors , Animals , Botulinum Toxins, Type A/antagonists & inhibitors , 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 , RatsABSTRACT
INTRODUCTION: The most frequently occurring long-term complication in implant-based breast reconstruction is fibrotic capsule formation at the recipient site, with concurrent dysesthesia and poor aesthetic results. Using porcine acellular dermal matrix (PADM) as a connective tissue graft material is supposed to improve the quality and quantity of soft tissue in implant-based breast reconstruction. This study investigates the indications for and the results and the costs of using PADM for the correction or prevention of implant-associated breast deformities. MATERIALS AND METHODS: This study reviewed a single surgeon's experience in the correction or prevention of implant-associated breast deformities with PADM in breast cancer-related breast reconstruction from 2009 to 2011. A total of 23 patients (27 breasts) were included in the study. The aesthetic outcome, the incidence and the type of complication were analysed. Twenty-three women underwent breast cancer-related breast reconstruction: 19 women underwent single-breast reconstruction and four women underwent bilateral reconstruction. RESULTS: Of the 23 patients who underwent breast reconstruction, 18 (78%) were "satisfied" with the aesthetic and haptic outcome after implant-based reconstruction with PADM. One patient (one breast) required another breast operation because of ipsilateral breast cancer recurrence during the follow-up period. PADM-assisted implant-based breast reconstruction has a satisfactory safety profile. CONCLUSION: The use of PADM as an interface matrix for implant-based breast reconstruction yielded predictable and acceptable aesthetic and haptic results by preventing capsular contracture, rippling, implant malposition, soft-tissue thinning and failure of the silicone implant-based breast augmentation.
