Time-course of analgesic effects of botulinum neurotoxin type A (BoNTA) on human experimental model of pain induced by injection of glutamate into temporalis muscle

Abstract

Abstract Background/aims Analgesic effects of BoNTA develop within few hours in animal studies and within days in human studies. We have previously shown that BoNTA can block glutamate-induced mechanical sensitization and neurogenic vasodilation in rat temporalis muscle within 3 h. The present translational study was designed to explore the time-course of analgesic effects of BoNTA on pain, sensitization and vasomotor responses in a glutamateevoked human pain model. Methods BoNTA (5U) and saline were injected (30 min interval) into the left and right temporalis muscles of 12 healthy males (24.2° 2 years). Pressure pain threshold (PPT), skin temperature (thermo camera) and tissue perfusion (laser Doppler flowmetry) were measured every hour for 3 h. Afterwards, subjects received an intramuscular injection of glutamate (1M– 0.2 mL) into the left and right temporalis muscles. Pain intensity (VAS) was recorded for 10 min after injection and pain distribution was then mapped. PPT was measured at 15 and 30 min following the glutamate injections, while skin temperature and tissue perfusion were recorded at 5, 15 and 30 min. Results This preliminary data showed that BoNTA significantly reduced glutamate-evoked peak pain intensity compared with saline (P = 0.042). Expansion of pain area was also smaller in the muscles pretreated with BoNTA (P = 0.045). Glutamate-induced vasomotor reactions (elevated skin temperature and tissue perfusion) showed a tendency to decline in BoNTA-pretreated muscles. A similar pattern was seen in terms ofmuscle sensitivity with higher PPT values in BoNTA-pretreated muscles. Conclusions BoNTA induced a direct analgesic effect withi 3 h of its injection into the temporalis muscle. This phenomenon, at least in part, might be through BoNTA actions on nociceptors. Present data also indicated that BoNTA attenuated glutamateinduced muscle sensitization and vasomotor reactions. This finding may suggest additional effects of BoNTA on the pattern of release of substances which are involved in pain pathways.