Botulinum Neurotoxins and Cancer—A Review of the Literature

Abstract

Botulinum neurotoxins (BoNT) possess an analgesic effect through several mechanisms including an inhibition of acetylcholine release from the neuromuscular junction as well as an inhibition of specific pain transmitters and mediators. Animal studies have shown that a peripheral injection of BoNTs impairs the release of major pain transmitters such as substance P, calcitonin gene related peptide (CGRP) and glutamate from peripheral nerve endings as well as peripheral and central neurons (dorsal root ganglia and spinal cord). These effects lead to pain relief via the reduction of peripheral and central sensitization both of which reflect important mechanisms of pain chronicity. This review provides updated information about the effect of botulinum toxin injection on local pain caused by cancer, painful muscle spasms from a remote cancer, and pain at the site of cancer surgery and radiation. The data from the literature suggests that the local injection of BoNTs improves muscle spasms caused by cancerous mass lesions and alleviates the post-operative neuropathic pain at the site of surgery and radiation. It also helps repair the parotid damage (fistula, sialocele) caused by facial surgery and radiation and improves post-parotidectomy gustatory hyperhidrosis. The limited literature that suggests adding botulinum toxins to cell culture slows/halts the growth of certain cancer cells is also reviewed and discussed.

Botulinum Toxin in Movement Disorders: An Update

“…BoNT also downregulates sensory receptors, such as transient receptor potential cation channel subfamily V member 1 (TRPV1), also known as the capsaicin receptor and the vanilloid receptor 1, and purinergic (P2X3) receptors [ 280 ]. BoNT’s effects on these transmitters and receptors is being explored in the management of autonomic and pain disorders such as those associated with cancer [ 281 ].…”

Mobilizing Toxins for Cancer Treatment: Historical Perspectives and Current Strategies

“…The anticoagulants tyrofabin and hirudin, for example, originate from venom of the African saw-scaled viper and leech secretions, respectively [1]. Even pathogenic bacteria typically considered harmful to healthy tissue may prove to be clinically useful as studies have shown that toxins produced by these organisms can be manipulated to target aberrant cells in a tissue-or cell-specific manner [2][3][4][5].…”

“…In this Special Issue, we explore how toxins may be used as powerful treatments against certain cancers. The compiled articles cover how naturally-derived poisons can be utilized for cancer therapy on multiple levels, from interrogating cytotoxic pathways in different cell types, to exploiting toxic derivatives for pain relief in patients suffering from radiation sickness [3,5]. The Special Issue presented this month helps to expound upon this field of research and demonstrate the potential for its clinical applicability.…”

“…Studies of pain induced by radiation and/or surgery suggest that the local injection of BoNT improves neuropathic pain and local muscle spasm in the direct vicinity of the site of surgery and/or radiation. However, this type of pain-management therapy requires blinded and placebo-controlled studies to confirm its efficacy [5]. The results from various studies investigating the use of BoNT as an anti-tumor therapeutic also show promise.…”

“…Aside from direct applications as cancer treatments, toxins could be used to mitigate pain directly caused by tumor pressure, or neuropathic pain as a side effect of radiation or surgery in cancer patients [ 5 ]. Many clinical studies [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ] have investigated the use of botulinum neurotoxins (BoNT) as potent systemic analgesics, as these toxins block acetylcholine release from the neuromuscular junction or inhibit neurotransmitters at both peripheral and central sensory levels [ 39 , 40 , 41 , 42 ].…”