Botulinum toxin could offer an effective new treatment for two forms of neuropathy -- pain caused by different types of nerve injury, according to an experimental study published in Anesthesia & Analgesia.
Treatment with botulinum toxin type B (BoNT-B) produces lasting reduction in abnormal pain responses caused by physical nerve injury or chemotherapy-related nerve damage in mice, reports Tony L. Yaksh, Ph.D., of University of California, San Diego, and colleagues. Their study shows differing effects of local versus spinal injection of botulinum toxin and lends new insights into the molecular-level explanations for how "Botox" works to affect pain processing.
Further Studies on Botulinum Toxin's Effects on Pain Responses
Building on previous studies, the researchers performed experiments in mice to evaluate the effects of BoNT-B on exaggerated pain responses to touch (allodynia) in one or both hind paws after nerve injury. Mononeuropathy (single nerve injury) was induced by cutting a single spinal nerve and polyneuropathy (multiple nerve injury) by giving the chemotherapy drug cisplatin.
For both types of neuropathy, the study evaluated the effects of injecting BoNT-B directly into the affected paw or into the spine (intrathecal injection). Botulinum toxin is most familiar from the use of BoNT-A -- commonly known by the trade name Botox -- for cosmetic plastic surgery. Both BoNT-A and BoNT-B are used for treatment of various neuromuscular disorders.
Over the past decade, BoNT-A has been successfully used to treat certain chronic pain syndromes. Since botulinum toxin causes temporary muscle paralysis, the pain-reducing effects have been attributed to muscle relaxation. However, recent studies have suggested that other analgesic mechanisms may be operating as well.
In mononeuropathy, injecting BoNT-B into the affected paw significantly reduced abnormal pain responses. In polyneuropathy, local BoNT-B injection reduced allodynia in the injected paw only. This shows that the effects of locally injected botulinum toxin aren't due to more general spread of the toxin.
The reduction in allodynia after local BoNT-B injection lasted about two weeks before wearing off. That's consistent with the temporary effect of botulinum toxin used for other purposes -- the injections must be repeated to sustain the beneficial effects.
In polneuropathy, intrathecal injection of BoNT-B relieved the allodynia on both affected sides. Spinal BoNT-B didn't alter normal reflexes in the paws, and didn't alter other types of pain perception.
Cellular-level studies showed that the two types of BoNT-B injection had differing effects in the pain-processing centers of the spinal cord. The results provided new insights into the specific molecular targets involved in local and intrathecal injection.
Neuropathies are common and difficult-to-treat chronic pain problems. Mononeuropathy results from nerve injury of many possible causes -- for example, spinal cord injury or other trauma. Polyneuropathy can occur as a toxic effect of chemotherapy drugs, although diabetes is the most common cause.
The findings add to previous studies suggesting that botulinum toxin could be a useful new approach to treating neuropathic pain. They aid in understanding BoNT's mechanisms of action in mononeuropathy versus polyneuropathy, as well as the differing effects of local and spinal injection.
The study is also one he first to focus on BoNT-B, which is shorter-acting than BoNT-A. Dr. Yaksh and colleagues conclude, "Further work focusing on transport and uptake of these and other BoNT serotypes will likely provide important insights into the mechanisms whereby these toxins exert their effects upon nociceptive [pain] processing."
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