Human Studies

Botulinum toxin A (BTX-A) is a promising therapeutic modality against trigeminal neuralgia (TN) with certain controversies pertaining to its application. To provide further information on factors influencing the treatment outcomes of BTX-A, a retrospective study with 152 patients with TN treated with BTX-A was performed. The starting time and duration of the therapeutic effect, as well as side effects, of BTX-A in the treatment of TN were analyzed by sex, age, course of disease, number of branches and injected dose. A total of 136 patients exhibited symptom improvement within 2 weeks following BTX-A treatment as evaluated using a visual analog scale (VAS). The effect of BTX-A was sustained throughout the initial 6 months of the follow-up and was demonstrated to persist for as long as 28 months. Female sex, short disease course and high injection dose (>70 units) were associated with lower long-term VAS scores. Patients receiving short-term medium-(50-70 units) or high-dose injections were more likely to be completely cured. Patients with a median disease course (1-10 years) or multiple branches were more likely to exhibit facial asymmetry. Based on the stratified analysis, female patients with a median disease course (1-10 years) exhibited a higher incidence of side effects and male patients achieved better treatment outcomes with high BTX-A doses. BTX-A effectively alleviated patients with TN in both short or long term, although the treatment efficacy may depend on patient characteristics.

Preclinical studies suggest that type 2 hyperpolarization-activated cyclic nucleotide gated ion channels (HCN2) are necessary for neuropathic pain. This trial assessed the influence of ivabradine, a non-selective HCN channel blocker, on capsaicin-induced hyperalgesia and pain in healthy human subjects. An enriched population comprising subjects who developed >20cm2 of punctate hyperalgesia from topical capsaicin (0.5% cream applied onto 9cm2 area) was identified. These subjects then received ivabradine (15mg) or placebo one hour prior to capsaicin application in randomly allocated order in a crossover study. The forearm site for capsaicin alternated with each application of the cream. The interval of time from screening to the 1st and to the 2nd treatment visits were at least 3 and 5 weeks respectively to minimize carry-over effects. 55 participants were screened, of which 25 completed at least one treatment visit. Intention-to-treat hierarchical analysis revealed no significant effects of the drug on primary trial outcome, defined as a difference in effects of placebo and ivabradine on the area of punctate hyperalgesia (ivabradine – placebo: mean=3.22 cm2, 95% CI: = -4.04, 10.48, p=0.37). However, ivabradine caused a slowing of heart rate (difference of 10.10 beats per min (95% CI – 6.48, – 13.73; p-value <0.0001)). We conclude that ivabradine lacks analgesic effects in the capsaicin pain model at a dose that caused appreciable slowing of heart rate, and hence is unlikely to prove a useful analgesic in humans. More selective drugs are required to establish a role of HCN2 for pain in humans.