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15 Articles in Volume 18, Issue #5
Chronic Pelvic Pain: The Need for Earlier Diagnosis and Diverse Treatment
Cross-Linked Hyaluronic Acid for the Management of Neuropathic Pelvic Pain
Fentanyl: Separating Fact from Fiction
Gender Bias and the Ongoing Need to Acknowledge Women’s Pain
Letters to the Editor: 90 MME/day Ceiling; Ehlers-Danlos; Redefining Pain
Post-Menopausal MSK Pain and Quality of Life
PPM Welcomes Dr. Fudin and Dr. Gudin as New Co-Editors
Practitioner as Patient: Understanding Disparities in CRPS
States Take Action to Manage Opioid Addiction
Step-by-Step Injection Technique to Target Endometriosis-Related Neuropathic Pelvic Pain
The Many Gender Gaps in Pain Medicine
The Need for Better Responses to Vulvar Pain
Topical Analgesics for Chronic Pain Conditions
Topical Medications for Common Orofacial Pain Conditions
What’s the safest, effective way to taper a patient off of opioid therapy?

Topical Medications for Common Orofacial Pain Conditions

Topical applications for trigeminal neuralgia, painful post-traumatic trigeminal neuropathy, burning mouth syndrome, myofascial pain, and TMJ arthralgia. Plus, cannabinoid spray and traumeel in orofacial treatment.

Orofacial pain disorders comprise those painful conditions that affect the masticatory and cervical musculature, temporomandibular joints, intraoral structures, and the occipital, temporal, orbital, and frontal regions of the head. The diversity of pain complaints in this region often requires multidisciplinary management. As a result, patients may seek out practitioners from several specialties within medicine and dentistry for assessment and treatment. Having a basic understanding of these conditions may help patients avoid unnecessary office visits or diagnostic tests, as well as inappropriate treatments.

Orofacial pain disorders may be categorized as neuropathic, neurovascular, and temporomandibular joint (TMJ). Some of the most commonly treated conditions in a typical orofacial pain clinic may include: myofascial pain, trigeminal neuropathy, migraine, tension-type headache, chronic daily headache, TMJ arthritis and internal derangements, and burning mouth syndrome. Topical medications offer one modality with the following potential benefits compared to systemic approaches: topicals bypass first-pass metabolism; reduce systemic adverse effects; reduce potential for drug-drug interactions; provide direct, local analgesia; and improve patient compliance. This article provides a review of the topical medications currently used to treat orofacial pain, including their mechanisms of action and evidence supporting them, and provides insight into two emerging approaches: cannibinoids and traumeel.

Neuropathic Pain

Defined as “pain caused by a lesion or dysfunction of the somatosensory nervous system,”1 neuropathic pain is a chronic pain disorder resulting from injury to the nervous system. The injury may be to any site in the central nervous system (CNS) or the peripheral nervous system (PNS), and pain may vary in intensity. However, in many patients, the pain may be so severe that it impacts their quality of life and daily function.

Within the orofacial region, there are several diagnoses for neuropathic pain, including: trigeminal neuralgia, painful post-traumatic trigeminal neuropathy, burning mouth syndrome, post-herpetic neuralgia, trigeminal neuroma, and other neuropathies related to systemic diseases (eg, diabetes mellitus, cancer, drug-induced, HIV/AIDS-related).2 Described below, trigeminal neuralgia, painful post-traumatic trigeminal neuropathy, and burning mouth syndrome are the more common types of neuropathies seen in orofacial pain and dental practices according to the authors' practice and the literature.

Trigeminal Neuralgia

Trigeminal neuralgia is defined as a sudden, short-lived stabbing or electric shock-like pain affecting one or more of the branches of the trigeminal nerve (cranial nerve V). The characteristics of this disorder are so specific that the diagnosis is made by history alone, although brain imaging is sometimes necessary. Pain is paroxysmal, lasting from seconds to a few minutes.3 Trigeminal neuralgia may mimic tooth pain, and some patients report an intraoral trigger zone. While first-line treatment involves oral, medical management with carbamazepine, topical medications may also be effective. Specifically, topicals, such as 20% benzocaine, capsaicin, or a compounded formula of anticonvulsants, tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors, may be applied over an intraoral trigger zone (see below for more detail).

Painful post-Traumatic Trigeminal Neuropathy

Painful post-Traumatic Trigeminal Neuropathy (PTTN) is the term coined by the International Headache Society to describe neuropathic pain resulting from trauma to the trigeminal nerve.4 Historically, this type of pain has also been described as deafferentation pain, traumatic neuropathy, phantom tooth pain, and atypical odontalgia.4 PTTN affects approximately 2 to 3% of patients.5 Occurring intraorally, PTTN can be complex to diagnose and to treat. Usually, the pain is localized to the site of trauma, but the pain may move around the area as well.

The pathophysiology of PTTN involves both the peripheral and central nervous systems. Alterations to a damaged nerve may lead to the sprouting of neural fibers, causing increased nociception. These changes may be localized to the peripheral nerve and termed "peripherally sensitized." However, if central nerves become affected, then the nerves may be considered "centrally sensitized." PTTN results in normal sensory signals being perceived as painful. In a peripheral injury, there is upregulation of voltage-gated sodium (Nav1.3 and Nav1.8) and calcium (α2γ subunit) channels. In addition, there is often a down-regulation of potassium channels and a reduction in the threshold of heat sensitive channels. These changes may cause ectopic discharge, leading to increased release of glutamate and activation of the N-methyl-D-aspartate (NMDA) receptors located in the CNS. Furthermore, there is increased excitatory neurotransmitter release and decreased inhibitory neurotransmitter release, which facilitate the nociceptive response centrally. Sympathetic nervous system involvement may also be seen in neuropathic pain.6,7 All of these can serve as potential targets for pain management.

Topical Options for Trigeminal Neuralgia & PTTN

Treatment for trigeminal neuropathic pain conditions such as PTTN or neuralgia may involve both topical and systemic medications. When the injury only involves the peripheral branches of the nerve, topical medications such as those described below may be effective. However, when there is central sensitization, systemic medications are required. These include the usual classes prescribed for other neuropathies, such as anticonvulsants, tricyclic anti-depressants, serotonin, and norepinephrine reuptake inhibitors, or opioids.4,8

When there is an intraoral trigger zone for PPTN or trigeminal neuralgia, topical medications may be more effective due to their enhanced absorption via the oral mucosa versus the skin. Topical medications that have demonstrated significant pain relief in orofacial neuralgias and neuropathies include anesthetics, capsaicin, anticonvulsants, anti-inflammatories, α2-adrenergic agonists, and NMDA-receptor antagonists.9,10 In some cases, a compounded formula including some or all of these agents may be beneficial, but these formulations require the expertise of a pharmacist.

First-line topical medication options for trigeminal neuropathies include a topical anesthetic and/or capsaicin. Common topical anesthetics include benzocaine and lidocaine.9 The mechanism of action of these anesthetics involves inhibition of sodium channels. In trigeminal neuropathies or neuralgias, a thin layer of the topical anesthetic may be applied over the intraoral trigger zone. Topical anesthetics are usually mixed with a methylcellulose paste (orobase) in order to be absorbed transmucosally.9 This application may be repeated 4 to 6 times per day.

Clonidine: Clonidine is an α2-adrenergic agonist that provides potent analgesia. In neuropathic pain, α2 adrenoreceptors are upregulated and are sensitive to norepinephrine. Activation of α2 adrenoreceptors therefore inhibits the release of calcitonin gene-related peptide and glutamate, which play an integral role in nociception as neurotransmitters. Clonidine may be compounded into a cream and applied topically to provide pain relief. Systemic side effects include sedation and hypotension,10 requiring close monitoring.

Lidocaine: While evidence for the use of topical medications to treat trigeminal neuropathic pain is limited, a small case series of 14 patients treated for extraoral, trigeminal neuropathic pain with 5% lidocaine plasters showed improvement in 12 of the 14 patients.11 Two patients were able to stop their adjuvant medication completely, while nine were able to reduce their medication. The plaster (available in the United Kingdom) was comprised of 700 mg of lidocaine mixed with a polyethylene terephthalate backing. The topical was used 12 hours per day for 4 weeks.

Of note, randomized control trials examining other neuropathic pain conditions have shown benefit with local anesthetics as well. For example, a lidocaine 5% patch has been demonstrated to provide pain relief in post-herpetic neuralgia and other peripheral neuropathic conditions.8 Adverse effects are minimal and include erythema and rash. Systemic absorption is also limited with the approved maximum dosing recommendations.8 Lidocaine gel may also be effective in patients with post-herpetic neuralgia. However, in those with HIV-related neuropathy, it was not proven beneficial.8

Capsaicin: Capsaicin is a component of chili peppers. It binds to the nociceptor, TRPV1, which is located on polymodal C-fibers.12 Initially capsaicin works by increasing the production of inflammatory mediators, causing hyperalgesia. However, repeated application may cause prolonged activation of the TRPV1 receptor, rendering it dysfunctional.13 Capsaicin is available at low concentrations in over-the-counter creams. Vickers, et al. trialed patients diagnosed with atypical odontalgia (now referred to as PTTN) with an application of 0.025% capsaicin for 3 minutes twice a day, after local anesthetic application to the painful site. After 4 weeks, the authors found that 19 of 30 patients reported pain relief. After 3 months, their level of pain relief was maintained.14 Common adverse effects of capsaicin include nausea, dyspepsia, and initial increase in pain when applied topically.13,15 Pain relief is dose dependent and may last for several weeks.16 Capsaicin preparations at higher doses, such as the capsaicin patch 8%, have shown to be more efficacious than lower concentrations.16 Unfortunately, treatment is challenged by low adherence to this medication due to its side effects, particularly the burning pain associated with application.17

Compounded formulas: A large compounded formula may also be effective in managing neuropathic orofacial conditions by targeting different receptors involved in the pathophysiology of the disorder. In 2008, a retrospective study evaluated the treatment of various orofacial neuropathic conditions (deafferentation pain, traumatic neuroma, and trigeminal or glossopharyngeal neuralgia) with topical and/or systemic medication. The authors included 39 patients and found that those receiving treatment with topical therapy reported 40% pain reduction. The topical medication used was a compounded formula of:

  • carbamazepine 4% (a sodium channel blocker)
  • lidocaine 1%
  • ketoprofen 4% (a non-steroidal anti-inflammatory drug, or NSAID)
  • ketamine 4% (an NMDA-receptor antagonist)
  • gabapentin 4% (a calcium channel blocker).

These medications were mixed with anhydrous gels and bio-adhesive copolymers.18 Another study involving rats undergoing intraorbital nerve injury showed improvement with topical application of pregabalin 5% or 10%, diclofenac 5% (an NSAID); or both pregabalin 5% (a calcium channel blocker) and diclofenac 5% for 4 days.19

Burning Mouth Syndrome

Burning mouth syndrome (BMS) is a chronic, neuropathic pain condition affecting the tongue, hard palate, and oral mucosal membranes. It is described as a painful burning sensation over these tissues in the absence of any organic pathology. According to the International Headache Society, BMS is defined as “an intraoral burning or dysaesthetic sensation, recurring daily for more than 2 hours per day over more than 3 months, without clinically evident causative lesions.”20

Topical therapies for BMS: While burning mouth syndrome may be challenging to manage, topical application of clonazepam has shown to provide pain relief. Clonazepam is a gamma-aminobutyric acid (GABA)-A agonist, which enhances the inhibitory action of this neurotransmitter. This acts on both peripheral and central receptors, thereby causing central serotonergic modulation and reduction of central neuronal hyperactivity.21

Topical clonazepam may be applied through a swish-and-spit method. Staring with clonazepam 0.5 mg, the pill may be cut in half and dissolved in a small glass of water. The solution may then be rinsed in the mouth for 3 minutes and spit out. This regimen may be repeated three times daily.

Myofascial Pain/Myalgia

Myofascial pain, or myalgia, is a muscular disorder, falling under the umbrella of temoporomandibular joint disorders, and refers to pain caused by muscular trigger points and taut muscle bands. It is characterized by spontaneous dull, aching pain around a particular muscle leading to muscle stiffness and fatigue. Upon palpation, the provider typically palpates a hyperirritable spot within a taut band of muscle that exhibits pain referral when compressed. Patients may also show decreased range of motion and weakness of that muscle.22 There are multiple treatment modalities for myofascial pain, including topicals such as NSAIDs, anesthetics, and capsaicin cream, as outlined below.

Topical Options for Myofascial Pain

NSAIDS: The NSAID diclofenac inhibits the enzyme cyclooxygenase and ultimately leads to reduced inflammatory mediators (ie, prostaglandins, thromboxanes, and prostacyclins).23 It is available in several forms, including gels, patches, creams and lotions.16 A double-blind, placebo-controlled randomized study comparing a diclofenac sodium 60-mg patch and a control menthol patch in patients with cervical myofascial pain showed that patients using the diclofenac sodium patch had a greater reduction in pain scores and better functional outcomes. Adverse effects included skin irritation and erythema, but these were more prevalent in the control group.23

Diclofenac gel 1% may also be applied externally to the site of pain. Systemic absorption of both the gel and patch forms are significantly lower compared to a single oral 50 mg diclofenac dose.24 The recommended dose for the diclofenac gel used in the upper extremities (eg, hand, elbow, and wrist) is 2 g per joint application, with a maximum of 8 g per joint per day. Based on the size of the masseter and TMJ region, the recommended dose is 1 g up to 4 times per day. (Note: these dose recommendations are based on anecdotal reports. A patient should not use more than a total of 32 g of gel per day.24)

Other topical NSAID preparations such as ketoprofen, aspirin, and ibuprofen, may be made by a compounding pharmacy.2 Evidence is limited in the orofacial pain literature regarding the use of topical NSAIDs for masticatory myofascial pain. However, a recent systematic review found that topical diclofenac, ketoprofen, and piroxicam showed good pain relief for acute musculoskeletal (MSK) pain, such as for sprains or strains.25 Unfortunately, there is no evidence to date to show that topical NSAIDs are effective in the management of chronic MSK pain.26 Reported adverse effects with topical NSAIDs were minimal and no greater than those of the topical placebo.25 Topical NSAIDs may, however, be useful in patients who are susceptible to the gastrointestinal side effects of oral NSAIDs.

Anesthetics: The most widely used topical anesthetic for myofascial pain is the lidocaine patch 5%, which has shown to be effective in decreasing pain and improving quality of life.27 The lidocaine patch may be applied over 12 hours. The eutectic mixture of local anesthetic (EMLA) cream is a combination of 2.5% lidocaine and 2.5% prilocaine that is also available as a topical analgesic. Its recommended application is four times a day to the affected site.17 In addition, the 70-mg lidocaine/70-mg tetracaine patch offers another alternative. While the lidocaine 5% patch provides analgesia without anesthesia, the EMLA cream and lidocaine/tetracaine patch result in both analgesia and skin anesthesia.16

Capsaicin: Capsaicin cream offers another potential alternative for myofascial pain. In patients with soft tissue pain, capsaicin cream 0.05% has showed reduced pain scores compared to placebo.28 Overall, the capsaicin cream was well tolerated, however, those applying the capsaicin cream experienced more adverse events than those in the placebo group. While evidence for both topical anesthetics and capsaicin for the management of myofascial pain in the orofacial region is limited, studies of other muscle groups have shown benefit.

Temporomandibular Joint Arthralgia

TMJ arthralgia describes pain or tenderness on palpation of the temporomandibular joints. Arthralgia may be associated with disc displacements and osteoarthritis. Patients with disc displacements exhibit symptoms of clicking and locking. Disc displacements may be detected clinically on examination, as well as through imaging (eg, MRI) when needed. Those with osteoarthritis of the TMJs exhibit crepitus on joint function. Degenerative changes to the TMJs may be detected on imaging, such as a cone-beam CT. On examination, the joint noises in both disc displacement and osteoarthritis may be detected through auscultation.

Topical medications used to manage arthralgia include NSAIDs, anesthetics, and capsaicin cream. The class of medications and dosages are the same as those described above for myalgia and myofascial pain. Additional topical options are described below.

Diclofenac gel: Externally applied diclofenac gel 1% is often the first choice among topicals for arthralgia. The recommended dose is 1 g up to 4 times per day applied to the TMJ region, with a maximum dose of 32 g of gel per day.24 Topically applied diclofenac and oral diclofenac have been found to be equally effective in the treatment of TMJ disorder symptoms, with topically applied diclofenac having the advantage of little to no adverse systemic effects.29

Compounded NSAIDS: Sufficient, high quality evidence for compounded topical NSAIDs (eg, ketoprofen, aspirin, and ibuprofen) is scarce, however, a semi-recent systematic review evaluating these drugs for the management of pain due to TMJ degenerative joint disease described one double-blind, randomized, placebo-controlled trial that showed benefit.30 While there were no significant differences in pain relief between the other treatment groups, patients using the topical NSAIDs reported improvement compared to the placebo group.

Corticosteroids: Corticosteroids inhibit phospholipase A2, which prevents the conversion of lips to arachidonic acid, ultimately inhibiting the inflammatory cascade. They have a stronger anti-inflammatory effect than NSAIDs and may be utilized topically using ultrasound (phophoresis) or electrical current (iontophoresis), which drives the corticosteroid into the joint. Reid, et al. compared iontophoresis with dexamethasone in a lidocaine vehicle to placebo in patients with TMJ disorder. Three sessions were completed over 5 days, and patients were followed-up at 7 and 14 days. Compared to placebo, those receiving iontophoresis showed more improvement.31

Emerging Therapies in Orofacial Pain

Tetrahydrocannabinol and Cannabinol as a Spray

Cannabinoids have been identified as potential adjuvant analgesics and are currently under investigation for a variety of conditions, which may soon include orofacial pain. The natural cannabis plant (Cannabis Sativa L) contains more than 60 cannabinoids, including the potential therapeutic components known as tetrahydrocannabinol (THC) and cannabinol (CBD).

Tetrahydrocannabinol (THC)/Cannabinol(CBD) oromucosal spray is formulated from plant-based extracts prepared from the plant’s genetically distinct chemotypes and contains an approximately 1:1 ratio of THC:CBD, plus smaller amounts of other compounds, including minor cannabinoids and terpenes.32 THC/CBD spray is licensed in Canada for the treatment of central neuropathic pain in patients with multiple sclerosis (MS), as well as in the European Union, Israel, and New Zealand for relief of spasticity in MS. A 2014 study in Europe concluded that THC/CBD spray showed significant improvement in peripheral neuropathic pain.33 Another study found that THC/CBD spray was effective for the relief of intractable pain in patients who experienced inadequate analgesia despite chronic opioid treatment.34,35

Isolated in 1963, CBD lacks psycho-activity, and does not appear to bind to CB1 or CB2 receptors, but rather interacts with a multitude of various ion channels, enzymes, and other receptors that are believed to explain its analgesic, anti-nausea, anti-emetic, anti-epileptic, anti-inflammatory, anxiolytic, anti-ischemic, and anti-psychotic properties.36-40

With orofacial pain, CBD may be used topically or as an intra-oral spray for neuropathic pain, and/or as an anti-inflammatory agent.

Traumeel as an Integrated Approach

Traumeel is a homeopathic medication produced in oral, topical, and injectable forms. Its mechanism of action is that of an immune system modulator. The activity minimizes the negative effects of inflammation, while allowing aspects of the positive prostaglandin activities to occur. This action is contrary to cortisone, which simply suppresses the immune function. When used topically traumeel is readily absorbed and has been recommended for use with trauma, injuries, physical therapy, and soft tissue and inflammatory joint conditions.41

A fixed combination of plant and mineral extracts, traumeel may also be used to treat inflammation and pain caused by MSK injuries.42 Randomized clinical trials have demonstrated reductions in pain and swelling, and improvements in the mobility of joints, such as the ankle and knee.43-45 Traumeel has further demonstrated efficacy similar to conventional therapies, NSAIDS, and diclofenac.46-48 Traumeel is well tolerated and presents with very few adverse effects.49-51 Traumeel use for pain relief may offer an option without the risks of steroids, opioids, or NSAIDS, according to recent multicenter studies.52,53

While recent research regarding traumeel focused on the knee joint, traumeel ointment has been used for years to treat orofacial pain topically—as an anti-inflammatory agent. Anecdotally, it has been utilized for MSK pain as well as TMJ pain with favorable results.

Conclusion

Common orofacial pain disorders are diverse, including neuropathic pain, myalgia and myofascial pain, and temporomandibular joint arthralgia. While management of these disorders may be varied and often require multidisciplinary approaches, pharmacotherapeutics represent an important treatment option. Topical medications, in particular, may offer several advantages, including: reduced systemic side effects; lessened potential for drug-drug interactions; the ability to provide direct, local analgesia; and improved patient compliance.

Common topical medications used to manage orofacial neuropathic pain include: anesthetics; capsaicin; compounded formulas involving anticonvulsants, tricyclic antidepressants, clonidine, ketamine, and clonazepam. Effective topical agents for myalgia, myofascial pain and TMJ arthralgia include topical NSAIDs, anesthetics, and capsaicin. Topical corticosteroids may be applied for arthralgia as well.

Looking ahead, as research continues, cannibinoids and traumeel may soon offer alternative topical medications for the management of orofacial pain conditions as well.

Last updated on: August 1, 2018
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