Botulinum toxin type A to pericranial muscles
The pathogenesis of tension-type headache (TTH) is unclear and the role of muscle tension is especially controversial. The release of muscle tension in craniofacial muscle by injecting botulinum toxin type A into pericranial muscles probably plays a minor role in its experimental relief of TTH. It has been shown to block the release of glutamate, substance P, and calcitonin gene-related peptide, which may lead to decreased sensory central nervous system input and a reduction of headache.[31]Aoki KR. Evidence for the antinociceptive activity of the botulinum toxin type A in pain management. Headache. 2003 Jul-Aug;43(suppl 1):S9-15.
http://www.ncbi.nlm.nih.gov/pubmed/12887389?tool=bestpractice.com
The results of various double-blind, placebo-controlled studies have been mixed and the use of botulinum toxin for chronic TTH is not currently recommended.[46]Simpson DM, Hallett M, Ashman EJ, et al. Practice guideline update summary: botulinum neurotoxin for the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2016 May 10;86(19):1818-26.
http://n.neurology.org/content/86/19/1818
http://www.ncbi.nlm.nih.gov/pubmed/27164716?tool=bestpractice.com
[47]Silberstein SD, Gobel H, Jensen R, et al. Botulinum toxin type A in the prophylactic treatment of chronic tension-type headache: a multicentre, double-blind, randomized, placebo-controlled, parallel-group study. Cephalalgia. 2006 Jul;26(7):790-800.
http://www.ncbi.nlm.nih.gov/pubmed/16776693?tool=bestpractice.com
[48]Karadaş O, Ipekdal IH, Ulaş UH, et al. Botulinum neuro-toxin type-A in the treatment of chronic tension type headache associated with pericranial tenderness [in Turkish]. Agri. 2012;24(1):9-14.
http://www.journalagent.com/pubmed/linkout.asp?ISSN=1300-0012&PMID=22399123
http://www.ncbi.nlm.nih.gov/pubmed/22399123?tool=bestpractice.com
However, a more recent meta-analysis found that it was associated with significant improvements in standardised headache intensity, headache frequency, daily headache duration, and the frequency of acute pain medicine use compared with controls.[49]Dhanasekara CS, Payberah D, Chyu JY, et al. The effectiveness of botulinum toxin for chronic tension-type headache prophylaxis: a systematic review and meta-analysis. Cephalalgia. 2023 Mar;43(3):3331024221150231.
https://journals.sagepub.com/doi/full/10.1177/03331024221150231?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org
http://www.ncbi.nlm.nih.gov/pubmed/36786349?tool=bestpractice.com
Calcitonin gene-related peptide (CGRP) inhibitors
In clinical trials for migraine treatment, a reduction in non-migraine headaches (including TTH) has been observed with CGRP inhibitors.[50]Schou WS, Ashina S, Amin FM, et al. Calcitonin gene-related peptide and pain: a systematic review. J Headache Pain. 2017 Dec;18(1):34.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355411
http://www.ncbi.nlm.nih.gov/pubmed/28303458?tool=bestpractice.com
Further studies are needed to investigate a possible role for CRGP inhibitors in TTH prevention.[3]Ashina S, Mitsikostas DD, Lee MJ, et al. Tension-type headache. Nat Rev Dis Primers. 2021 Mar 25;7(1):24.
http://www.ncbi.nlm.nih.gov/pubmed/33767185?tool=bestpractice.com
Nitric oxide synthase inhibitors
Given the involvement of nitric oxide in triggering TTH, inhibiting its synthesis through targeted interventions could offer a novel therapeutic approach. Investigating the efficacy and safety of nitric oxide synthase inhibitors in clinical trials may provide valuable insights into their potential as a treatment option for individuals suffering from chronic TTH. Further research in this area is warranted to better understand the therapeutic benefits and mechanisms of action associated with nitric oxide synthase inhibition.[3]Ashina S, Mitsikostas DD, Lee MJ, et al. Tension-type headache. Nat Rev Dis Primers. 2021 Mar 25;7(1):24.
http://www.ncbi.nlm.nih.gov/pubmed/33767185?tool=bestpractice.com