Blockade of glutamate release by botulinum neurotoxin type A in humans: a dermal microdialysis study.
BACKGROUND
The analgesic action of botulinum neurotoxin type A (BoNTA) has been linked to the blockade of peripheral release of neuropeptides and neurotransmitters in animal models; however, there is no direct evidence of this in humans.


OBJECTIVE
To investigate the effect of BoNTA on glutamate release in humans, using an experimental model of pain and sensitization provoked by capsaicin plus mild heat.


METHODS
Twelve healthy volunteers (six men, six women) were pretreated with BoNTA (10 U) on the volar forearm and with a saline control on the contralateral side. Dermal microdialysis was applied one week later to collect interstitial samples before and after the application of a capsaicin patch (8%) plus mild heat (40°C⁄60 min) to provoke glutamate release, pain and vasodilation. Samples were collected every hour for 3 h using linear microdialysis probes (10 mm, 100 kD). Dialysate was analyzed for glutamate concentration. Pain intensity and skin vasomotor reactions (temperature and blood flow changes) were also recorded.


RESULTS
BoNTA significantly reduced glutamate release compared with saline (P<0.05). The provoked pain intensity was lower in the BoNTA-pretreated arm (P<0.01). The reduction in pain scores was not correlated with glutamate level. Cutaneous blood flow (P<0.05), but not cutaneous temperature (P≥0.05), was significantly reduced by BoNTA. There was a correlation between glutamate level and skin blood flow (r=0.58⁄P<0.05) but not skin temperature (P≥0.05). No differences according to sex were observed in any response.


CONCLUSIONS
The present study provided the first direct evidence supporting the inhibitory effect of BoNTA on glutamate release in human skin, which is potentially responsible for some of the analgesic action of BoNTA.
Larissa
L
Bittencourt da Silva
Ali
A
Karshenas
Flemming Winther
FW
Bach
Sten
S
Rasmussen
Lars
L
Arendt-Nielsen
Parisa
P
Gazerani
D000279:Administration, Cutaneous; D000328:Adult; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008297:Male; D017551:Microdialysis / Q000379:methods; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D012881:Skin Temperature / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects; D055815:Young Adult
D018698:Glutamic Acid; D019274:Botulinum Toxins, Type A