By Dr. Donald R. Tanenbaum
“All through the summer of 1946, Babe Ruth had a severe pain over his left eye. What was at first thought to be a toothache or sinus infection eventually caused so much discomfort that Ruth was admitted to a New York hospital. The doctors, suspecting that infected teeth were the cause, extracted three and then administered penicillin and other drugs. A month later though, Ruth was still in pain and still in the hospital.”1
As the months passed, Ruth’s pains were diagnosed as stemming from a nasopharyngeal carcinoma, providing evidence that the site of his early symptoms was not the source of his suffering. In essence, Ruth experienced what we now call heterotopic pain, when pain is felt at a site different from the injured or diseased organ or body part.
In the orofacial region, heterotopic pain is common. The definition offered by Merskey and Bogduk that “heterotopic pain is pain perceived in a region that has a nerve supply different from that of the source of pain,”2 has essential meaning when trying to identify the origins of often elusive tooth and/or jaw pain. Without this understanding, the practitioner is more apt to treat the teeth and jaw tissues though the reported symptoms, clinical evaluation findings and imaging may not provide sufficient clues to support these actions.
To fully understand the potential sources of heterotopic pain in the orofacial region, practitioners must not only become familiar with the concept of convergence from the caudate nucleus of the trigeminal system, but also must appreciate the underlying mechanisms differentiating nociceptive and non-nociceptive pain.
Over the years, pain has been defined in many different ways. One familiar definition states that “pain is a more of less, localized sensation of discomfort, distress or agony, resulting from the stimulation of specialized nerve endings, often associated with recognizable tissue injury or pathology.”3 This definition defines what is called nociceptive or somatic pain. “Nociceptive” means causing or reacting to pain – the cause of the pain comes from outside the nervous system, and a normally functioning nervous system reacts to it. In this model of pain, tissue injury which is always associated with inflammation and commonly initiated by trauma, disease, or chemical and thermal irritants, stimulates normally functioning specialized nerve endings (nociceptors) initiating the pain experience. The phenomenon of allodynia (when touch is pain) and hyperalgesia (when a mildly noxious stimuli produces more pain than is expected) are always associated with this type of pain and are the characteristic elements of what is called peripheral sensitization. 4
Muscle, joint and tooth pains are types of somatic/nociceptive pain. At the outset, the location where the patient describes the pain, is the source of the pain. This allows for predictable identification and successful treatment. If, however, the pain persists (pathology remains elusive due to its location like the nasopharynx) or is initiated by extreme trauma, then the initially purposeful peripheral sensitization leads to pain intensification and what is called a spreading receptive field. The end result is that the somatosensory cortex where pain perception occurs becomes “confused” and pain is perceived elsewhere other than it’s true source. To make matters more complicated, under the influence of persistent/intense nociceptive input, the central nervous system is altered, so that a patient actually becomes more sensitive and experiences more pain with less provocation. This is called central sensitization. 4 Most of our successes therefore occur when true somatic pain problems are identified within a short timeframe, when the source of injury is identified and removed, and the source of injury is not excessively traumatic.
Non-nociceptive pain or what has been called neuropathic pain is defined as pain that arises from injury, disease or dysfunction of the peripheral or central nervous system. “Non-nociceptive,” meaning the pain comes from within the nervous system itself often representing a circuitry malfunction particularly when occurring in the absence of a specific definable event or insult to nerve tissue. This is often referred to as inside out pain and has no purpose. Essentially our bodies alarm system becomes too sensitive allowing false alarms to be set off, despite normal stimulation of the nervous system. When these pains are focused in the face and jaws, the complaints may mimic a TM disorder or toothache but will not be responsive to conventional outside in treatments. Often times the history provided along with the descriptive symptoms (constant, ongoing, unremitting and distressing pain) and examination findings make the practitioner pause as something does not appear to fit.
Though from a historical perspective some patients clearly have suffered trigeminal nerve injury from dental and surgical interventions and /or other traumatic events, the majority present with histories that reveal a multitude of risk factors that by themselves are difficult to connect with an orofacial pain experience. This is where the story gets interesting.
Pain as a Neuro-Immune Phenomenon
In an attempt to understand what is happening to create continuous pathological pain in the absence of identifiable events, pain research has focused on the role of the immune system and particularly microglial activation. In the eyes of researchers, the pain experience is often the end result of the interaction of the nervous system with the immune system. 6 In a proposed pain model, glial cells in both the peripheral and central nervous system are thought to monitor the environment around neurons and regulate states of neuronal excitability. They essentially provide surveillance always looking for signs of cellular stress. When ‘functioning properly’, microglial cells exhibit restraint and only prompt the release of pro-inflammatory cytokines in the brain (which amongst other things amplify aches and pains) when commonly recognized sources of cellular stress like viruses are identified.7 Microglial cells, however, often beat by their own drum, prompting pain emergence and amplification in the presence of cellular stresses that had been initiated and ongoing due to seemingly less relatable factors such as insomnia, persistent life stressors, domestic PTSD, primary anxiety disorders, chemotherapy, medications used to treat ADD/ADHD, chronic neck inflammation, migraines, and chronic gastrointestinal inflammatory disorders to name a few. 8 Remarkably then, pain can emerge in the face, jaw and teeth and persist though recognizable somatic tissue injury was never there in the first place.
For clinicians evaluating patients with orofacial pain, it is essential therefore to determine if a) the pain has a nociceptive or non-nociceptive origin, b) whether or not heterotopic mechanisms have been triggered and c) enough information has been gathered to “know who the patient is” and identifying risk factors that may be responsible for a persistent pain problem. Once this information is determined, making a diagnosis will be greatly facilitated.
Donald R. Tanenbaum, D.D.S., MPH, is clinical assistant professor, Hofstra North Shore-LIJ School of Medicine; clinical assistant professor, Dept. of Oral & Maxillofacial Surgery, School of Dental Medicine at Stony Brook University; section head, Facial Pain and Dental Sleep Medicine Section, Dept. of Dental Medicine, Long Island Jewish Medical Center.
1- JADA,July 2008, Vol. 139:7, pp. 926-93
2- Merskey H and Bogduk N (eds.). Classification of chronic pain. Descriptions of chronic pain syndromes and definitions of pain terms, 2nd Edition Seattle: IASP Press, 1994. 240 pp.
3- Anderson DM,2002. Mosby’s Medical Dictionary. Sixth Edition. Mosby: A Harcourt Health Sciences Company, St. Louis. 1867 pp
4- Vardeh D.,Naranjo J.F. (2017) Peripheral and Central Sensitization. In: Yong R., Nguyen M., Nelson E., Urman R., Pain Medicine. Springer, Cham
5- Current Opin Anaesthesiology, Microglial role in the development of chronic pain. Suter MR, 2016, October: 584-9
6- Pathological and protective roles of glia in chronic pain, Milligan E. and Watkins L., Nat Rev Neuroscience, 2009 Jan 23-36
7- Glial Cells and Chronic Pain, Neuroscientist 2010, October; 16(5): 519 531,Romain- Dan Gosselin, Marc Suter, Isabelle Decosterd