INM-405 for the Treatment of Orofacial Pain
Overview
According to an Institute of Medicine Report: Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education and Research, pain is a significant public health problem that is estimated to have an economic cost in the United States of at least $560-$635 billion annually. This includes estimated total incremental costs of pain-related healthcare ranging from $261-$300 billion and $297-$336 billion due to lost productivity.
Further, according to the American Academy of Pain Medicine’s “AAPM Facts and Figures on Pain”, chronic pain affects far more Americans (est. 100 million) than diabetes (est. 26 million), coronary heart disease (est. 16 million) and cancer (est. 15 million) combined. The global pain management market for pharmaceuticals and medical devices is estimated to exceed $36 billion in 2017, according to an August 2017 report from BCC Research.
Chronic pain can be categorized as either nociceptive (such as muscle pain), neuropathic (nerve pain such as pinched nerves in the lower back), and psychogenic pain (such as fibromyalgia). Each has different sensations, origins and potential treatment modalities. Other categories of pain include breakthrough pain, phantom pain, incident pain and others. Acute pain may follow any one of these categories.
General Categories of Pain
Nociceptive pain is caused by stimulation of sensory nerve fibers that respond to stimuli approaching or exceeding harmful intensity (nociceptors) and may be classified according to the mode of noxious stimulation. The most common categories are “thermal” (e.g., heat or cold), “mechanical” (e.g., crushing, tearing, shearing, etc.) and “chemical” (e.g., iodine in a cut or chemicals released during inflammation).
Neuropathic pain is caused by damage or disease affecting any part of the nervous system involved in bodily feelings (the somatosensory system). Peripheral neuropathic pain is often described as “burning”, “tingling”, “electrical”, “stabbing”, or “pins and needles”. Bumping the “funny bone” elicits acute peripheral neuropathic pain.
Psychogenic pain, also called psychalgia or somatoform pain, is pain caused, increased, or prolonged by mental, emotional, or behavioral factors. Headache, back pain, and stomach pain are sometimes diagnosed as psychogenic. Those that suffer from these conditions are often stigmatized, because both medical professionals and the general public tend to think that pain from a psychological source is not “real”. However, specialists consider that it is no less actual or hurtful than pain from any other source.


Orofacial Pain
According to a September 2016 fact sheet from the International Association for the Study of Pain, one type of chronic pain that may lend itself well to topical therapy is a subset of neuropathic pain called orofacial pain. In this category, InMed is currently focusing on two particular conditions: temporomandibular disorders (TMD) and trigeminal neuralgia (TN).
Both conditions are rooted in the trigeminal nerve that services the head and eyes (ophthalmic nerve), the cheek/upper lip (maxillary) and the side of the face/mandible joint/jaw (mandibular). Orofacial is common and has many causes. Several orofacial pain types are attributed to mechanical or neural injury near the surface of the skin, and this includes TMD and TN.
TMD encompasses a group of musculoskeletal and neuromuscular conditions involving the temporomandibular joint, or TMJ, masticatory muscles, and associated tissues. TMD pain can be associated with biomechanical dysfunction of the TMJ. TMD-related facial pain has been reported in 5-12% of the general population (with a female:male ratio of 2:1), according to the National Institute of Neurological Disorders and Stroke’s fact sheet on trigeminal neuralgia, but only 4%-7% seek treatment. While often mild in nature, progression to severe and/or chronic pain is associated with greater stress and comorbidities and often results in significant loss of work and increase in other healthcare related costs. Typical pharmaceutical interventions include oral (systemic) NSAIDs such as ibuprofen and low-dose antidepressants.
In contrast, TN can be much more severe. TN is a unilateral painful disorder that is characterized by brief, electric-shock-like pain and is abrupt in onset and termination. TN originates at the stem prior to the nerve dividing into the three individual nerves and thus can affect the entire orofacial region. TN is a rare disease and studies on prevalence are scarce. According to a May 2005 publication from Manzoni, et al., entitled “Epidemiology of typical and atypical craniofacial neuralgias”, data suggest that TN has an incidence in the general population of between 4 to 5 per 100,000 people, but some estimates range as high as 20 per 100,000 people in persons over 60 years of age. The ratio of women:men is 3:2, with a higher proportion seeing onset after the age of 40 and a higher incidence in patients with multiple sclerosis. Depending on severity and frequency, various surgical interventions are common. Typical pharmaceutical interventions include the anticonvulsant carbamazepine, although use of botulinum toxin to block nerve sensation and opioids to numb sever pain are common.