The role of BTX-A in the treatment of drug-refractory trigeminal neuralgia has been evaluated by some authorities [9, 13, 14], and it was found to be an effective treatment with the majority of the patients reporting a reduction or even disappearance of the pain. BTX-A was found to be effective in combination with pharmacotherapy, prior to considering more invasive therapies such as surgery or gamma knife radiosurgery. As such, BTX-A is a particularly valuable treatment for elderly patients and those with adverse anesthetic comorbidities [8, 15]. However, these studies included small patients number or of low-quality RCTs .
The mechanism by which BTX-A exerts its antinociceptive effect is poorly understood; whether or not BTX-A can change sensory perception in those patients remains unknown . Cui et al . demonstrated that subcutaneous BTX-A injection is associated with the inhibition of formalin-induced glutamate release; an important mediator for the induction and maintenance of central sensitization of pain . BTX-A may also reduce the peripheral nociceptive input by inhibiting the release of substance P and calcitonin-gene-related peptide (CGRP), both of which would play a very important role in neurogenic inflammation [20–22]. Moreover, BTX-A can reduce the release of other neurotransmitters and neuromediators including epinephrine and norepinephrine . The effect of BTX-A has also an indirect central action through centrally mediated signal transduction to the spinal trigeminal nucleus [24, 25]. Another direct effects on muscle nociceptors and alteration of afferent derived from muscle spindle might play a role according to Arezzo  especially in reducing the myofascial pain by inhibiting muscle spasms-pain cycle.
The results of the current study support the possible role of BTX-A in pain alleviation, evidenced by the significant reduction in the mean VAS scores as well as the paroxysms frequency in BTX group in week 2 which continued till the endpoint LOCF, in addition to the significant increase in QoL functioning scale compared to the placebo group. Similar to our data, Pioversan et al.  reported significant pain reduction in 13 patients with trigeminal neuralgia within a period of 10 days; while in 20 days, patients did not exhibit any obvious symptoms. Some other studies reported a significant effect within 1–2 weeks with a maximum effect within 4–6 weeks [9, 14]. The long-term efficacy and its stability of its effectiveness of BTX-A in TN was elaborated in two studies [13, 28] which suggested that the effect of a single BTX-A injection could last for 6 mo (24 weeks), whereas other studies showed waning of efficacy started from the 8th week after treatment .
In our series a mean of 5 units /cm2 was injected with a mean total dose of 48 units. In Pioversan et al.  study, the Mean BTX-A dose was 3.22 units/cm2. An open label study assessed the clinical effects of BTX-A injections in 12 patients with otherwise unresponsive idiopathic trigeminal neuralgia. Patients were infiltrated with 20–50 units of BTX-A in trigger zones. The patients were assessed on a weekly basis using the Visual Analogic Scale for pain. Ten patients reported a significant benefit from BTX-A injections, with reduction or even disappearance of pain, and remained pain free for as long as 60 days . In another open-ended study to investigate, 8 patients with refractory trigeminal neuralgia were administered 100 U BTX-A through an injection into the zygomatic arch. The study concluded that BTX-A was quite effective in treating trigeminal neuralgia without the risk of excessive side effects . In our assessment of total BTX-A dosages used and drug efficacy measures, we could not find a significant correlation, which could be attributed to the fixed dose per site regimen adopted in our series, thus further evaluation of using different dosages per site can be a point of investigation.
Regarding safety of the BTX-A in the current study, side effects were generally tolerated and were mostly related to the injection sites, 4 cases developed mild facial asymmetry which was self limited and did not impose much impact on the patients especially in the setting of reduced pain. However, this adverse event could be overcome by a more posterior injection approach.