The Effect of Botulinum Toxin A on Headache Attributed to TMD

Temporomandibular Disorders (TMD) is a collective term, embracing a number of clinical
problems that involve the masticatory muscles, the temporomandibular joint (TMJ) and the
associated structures. The prime manifestation consists of pain of a persistent, recurring,
or chronic nature . Pain-related TMD can affect the individual's daily activities,
psychosocial functioning, and quality of life . The prevalence of TMD is about 10 % in the
general population, making it the second most common musculoskeletal condition, after chronic
lower back pain, that results in pain and disability . It has been estimated that the annual
TMD management cost in the USA, excluding diagnostic imaging, in the last decade was
approximately $4 billion.

The pathophysiology of pain-related TMD is poorly understood. However, multiple risk factors
have been identified, such as, gender, pain during jaw function and palpation, oral
parafunctions, other pain conditions, pain sensitivity and psychosocial characteristics.
Because of its multifactorial nature, a multimodal conservative treatment approach is
recommended, including patient education, behavioral management, physical therapy,
pharmacotherapy, and occlusal splints.

Among the pain-related TMD conditions are "Headaches Attributed to TMD". This diagnosis has
replaced "Headaches or facial pain attributed to Temporomandibular Joint (TMJ) disorder"
described in the International Classification of Headache Disorders II (ICHD-2). It is
characterized by pain in the temple area secondary to pain-related TMD that is modified by
function and parafunction affected by jaw movement, function, or parafunction.

In general, headache treatment is either abortive or prophylactic. Abortive treatment manages
acute headache and prophylactic treatment aims to reduce the frequency and severity of the
attacks. Intramuscular injections with Botulinum Toxin (BTX) are used in the prophylactic
treatment of migraine and tension type headaches. The mechanisms by which the analgesic
effects of BTX are mediated are not fully understood. One mechanism is the inhibition of
neurogenic inflammation by blocking neurotransmitter release from sensitized nociceptors,
thus reducing peripheral sensitization. In vitro, BTX has been found to inhibit Calcitonin
Gene-Related Peptide (CGRP), and BTX reduces the vascular response to algogenic substances
such as capsaicin applied to human skin. Other potential analgesic mechanisms include
retrograde transport of BTX by sensory neurons and inhibition of neurotransmitter release by
their central terminals.

In recent years, BTX has also been used in the treatment of myogenous-TMD with mixed results.
Two randomized controlled trials (RCTs) showed therapeutic benefits of BTX in the management
of myogenous -TMD, while another 3 RCTs reported no significant effect of BTX in chronic
myogenous -TMD pain. Varying patient samples, methodologies, and sample sizes may explain the
differences. Additionally, the results have been compromised by poor methodologies, such as
insufficiently powered clinical trials, and open-labeled studies. More recently, a systematic
review of randomized controlled trials concluded that no consensus could be reached on the
therapeutic benefit of BTX on TMD. More so, no trial on the effectiveness of BTX on the
prophylactic treatment of headaches attributed to TMD has been reported to date.

The purpose of this study is to determine the effectiveness of Botulinum toxin - A in the
management of headaches attributed to TMD.

Study Design The study will be carried out in the clinics of TMD and Orofacial Pain, School
of Dental Medicine, University at Buffalo. A prospective open label design will be used to
assess the effectiveness of BTX in the management of Headaches Attributed to TMD.

Recruitment will be done through advertising throughout the clinic and the community.

Inclusion Criteria:

- Adults age 18 to 74 years old.

- Participants with Headaches Attributed to TMD based on Diagnostic Criteria for TMD
(DC-TMD) criteria.

- A minimum of 15 headaches/events per month, for the last 3 months.

- Average pain intensity in the last month of ≥5 (0 to 10 scale) where 0 is no pain and
10 is the worst pain ever.

Exclusion Criteria:

- Pregnancy

- Participants with a history of neurological/neuromuscular disorders and bleeding
disorders.

- Participants taking prescribed analgesics, muscle relaxants, amino glycosides, or
anticholinesterases.

- Participants currently under BTX treatment.

- Participants currently under active treatment for TMD during the last month, which
includes physical therapy and pharmacological management.