The effect of peripheral administration of botulinum toxin type A in rats with neuropathic pain

Abstract

There are many trigeminal neuropathic pain (TN) patients in the world and they are suffering severe chronic pain. These patients are taking central acting drugs with severe side effects that make it difficult for the patients to continue the drugs. Our final goal is to develop new treatment methods that decrease chronic pain without severe side effects. To decrease the central side effects, our target is peripheral sensory ganglia. Experimental animal models of TN and sciatic neuralgia have been developed. We investigated the changes of mechanical allodynia after injecting newly developed botulinum toxin type A (150 kDa) (BoNT) peripherally to rats with sciatic nerve entrapment (SNE) or infraorbital nerve constriction (INC). SNE was induced by placing three Tygon® cuffs around the sciatic nerve, and INC was induced by ligating loosely around the infraorbital nerve. After SNE or INC induction, significant decreases of withdrawal thresholds to mechanical stimulation (Model 1601C, IITC Instruments) were observed in the hindpaw or face. Peripheral intradermal injection of BoNT, which is reported to block vesicular neurotransmitter release, recovered the withdrawal thresholds. These results suggest that SNE or INC rat models show neuropathic pain signs and BoNT decreases the neuropathic pain by decreasing the neurotransmitter release. Supported by Science and Culture in Japan 18390512 and Ryobi Teien Memorial Foundation.