This chapter is focused on analgesic mechanism of action of botulinum toxin type A (BoNT-A) including the action beyond peripheral nerve endings. With the exception of the meninges and possibly urinary bladder, the presence of BoNT-A activity in the periphery, cleaving SNAP25 as a target molecule, up to now was not convincingly shown. In contrast many reports demonstrated BoNT-A activity and the presence of cleaved SNAP25 in the brain and spinal cord. In a model of mirror pain BoNT-A analgesic effect can be achieved even without participation of peripheral nerve ending. Thus generalized hypothesis central or peripheral mechanism of action belongs to history, and there is a need to confirm or dispute the results with meninges, urinary bladder, and possibly with other, especially visceral organs.There are two general options for the central actions of BoNT-A: 1. The activity ends by silencing primary sensory neuron thereby stopping the pain information further in the CNS. 2. Or thereafter, indirectly or transsynaptically, BoNT-A triggers smaller or larger neural loops, forming memory of pain in the CNS that could explain the bilateral effects after unilateral peripheral administration, similar effect in mirror image allodynia and the like Intensive research has shown that peripherally administered BoNT-A reaches the CNS by axonal transport. There is increasing evidence that BoNT-A is preventing pain in a growing range of disorders. In the absence of unexpected findings, or an increase in the uncontrolled use of illicit preparations by uneducated persons, BoNT-A is emerging as a new long-lasting and relatively safe analgesic.