The antigenicity of commercially available botulinum toxin (Botox) has been a dose-limiting factor for its clinical use. The antigenicity can be reduced by the removal of non-toxic component (BoNT/A). Here we demonstrate that BoNT/A is endocytosed and axonally transported by the trigeminal ganglion (TG) neurons and attenuates the magnitude of pain-related behaivior in a rat model of neuropathic pain. The analgesic effect of BoNT/A was evaluated by subcutaneously injecting the neurotoxin into the vibrissal pad of rats with a chronic constriction injury of the infraorbital nerve. Thermal testing was based on Neubert et al. (Pain. 2005). Fasted rat's desire to obtain a food reward was coupled to its ability to tolerate facial contact with a warm (45 °C) thermode. The neuropathy decreased the ratio of thermode contact duration / event. One week after the injury subcutaneous BoNT/A reduced the incidence of facial contacts and increased the duration / event indicating decreased thermal hyperalgesia. To confirm the axonal transport of subcutaneously administered BoNT/A, BoNT/A heavy chain (membrane binding subunit of BoNT/A) was labeled with Thiol-Reactive Probes and injected into the facial skin. Two hours later BoNT/A was detected in TG neurons. This label was inhibited by colchicine treatment. In conclusion, subcutaneous BoNT/A was axonally transported by TG neurons and reduced neuropathy symptoms.