Botulinum Toxin A in Patients With Myofascial Pain Syndrome With and Without Zinc Supplementation

Overview

Research question: Dose the use of oral zinc supplement improve the effects of botulinum toxins injection in patients with myofascial pain dysfunction syndrome? Statement of the problem: MPDS Patients treated with botulinum toxin A injection usually suffers from return of the symptoms which requires successive injections almost every (3-4M) Rationale for conducting the research: The concept of adding the zinc supplementation prior to BTXA injection is contributed to the fact that botulinum toxin is a zinc-dependent metalloprotease; therefore, every botulinum toxin molecule must be accompanied with a zinc molecule to effectively paralyze a muscle. However, commercially available BTXA preparations exclude zinc from their preparations, and BTX clinical efficiency and duration varies according to the zinc levels of the patient. Although the BTX effect could remain for several months, its zinc-dependent proteolytic activity befalls within hours of administration before the toxins are degraded in the tissues. Therefore, for achieving better results from BTX, the recipients should have adequate zinc levels at the time of administration. Therefore, oral zinc supplement intake prior to BTXA injection may enhance its clinical efficiency and duration. botulinum neurotoxins are the most potent toxins known. They bind to nerve cells, penetrate the cytosol and block neurotransmitter release. Comparison of their predicted amino acid sequences reveals a highly conserved segment that contains the HExxH zinc binding motif of metalloendo peptidases. The metal content of tetanus toxin was then measured and it was found that one atom of zinc is bound to the light chain of tetanus toxin. Zinc could be reversibly removed by incubation with heavy metal chelators. Zn2+ is coordinated by two histidines with no involvement in cysteines, suggesting that it plays a catalytic rather than a structural role. Bound Zn + was found to be essential for the tetanus toxin inhibition of neurotransmitter release in Aplysia neurons injected with the light chain. The intracellular activity of the toxin was blocked by phosphoramidon, a very specific inhibitor of zinc endopeptidases. Purified preparations of light chain showed a highly specific proteolytic activity against synaptobrevin, an integral membrane protein of small synaptic vesicles. The present findings indicate that tetanus toxin, and possibly also the botulinum neurotoxins, are metalloproteases and that they block neurotransmitter release via this protease activity. So The use of zinc supplementation prior to BTXA injection has been suggested by several previous studies to prolong its duration of action as well as improve its efficacy

Myofascial pain syndrome is a complex disorder of the musculoskeletal system with multifactorial involvement and diverse clinical presentations in several areas of the body It can affect the oro-cranio-facial region, with involvement of the temporomandibular area and masticatory muscles, and is then called myofascial pain dysfunction syndrome. Botulinum injections can improve blood flow to the muscles and release the nerve fibers compressed by abnormally contracting muscles, both of which may contribute to the cause of pain. In addition, botulinum injections can have an immediate effect owing to direct release of endogenous endorphins from introduction of the needle and alteration in the balance of central neurotransmitters; this is caused by local inhibition of pain peptides from sensory ganglions and nerve terminals, and anti-inflammatory and antiglutaminergic actions . Moreover, studies have shown that 3-10% of patients develop neutralizing antibodies with long-term adverse effects that include muscular atrophy. BTX clinical efficiency and duration varies according to the zinc levels of the patient. Although the BTX effect could remain for several months, its zinc-dependent proteolytic activity befalls within hours of administration before the toxins are degraded in the tissues. Therefore, for achieving better results from BTX, the recipients should have adequate zinc levels at the time of administration. Therefore, oral zinc supplement intake prior to BTXA injection may enhance its clinical efficiency and duration. Explanation for choice of comparators: BTX is offered as a solution for myofascial pain patients; nevertheless, it is not considered as a definitive long-term solution so we add the zinc supplementation prior to BTXA injection to increase the clinical duration as reviewed in literature review.