Key points

Overview

In 1924, 2 neurosurgeons, Frazier and Russell, described a syndrome of pain along the territory of the trigeminal nerve that did not fit into the classically known cranial neuralgias ( Fig. 1 ). This syndrome consisted of unilateral facial pain that lasted most of the day, was described as a severe ache, burning, or crushing sensation, and no autonomic abnormalities were noted. In fact, no abnormalities on examination or tests could be found. Today, this constellation of symptoms would fit into the diagnosis of persistent idiopathic facial pain (PIFP), or as it is more commonly called, atypical facial pain (AFP). AFP has an incidence of 1 in 100,000, affects mainly adults, and is equally distributed between men and women, although women present more commonly for treatment, with postmenopausal women being more frequent.

Algorithm for CIM treatment of chronic orofacial pain.

The etiology of PIFP remains unknown. At one point, it was believed to be psychogenic. Early reports of AFP suggested that more than two-thirds of patients had a comorbid psychiatric disorder. A role for female hormones was postulated, as more women present with this condition. Today, different neuropathic mechanisms are hypothesized to be responsible.

Overview

In 1924, 2 neurosurgeons, Frazier and Russell, described a syndrome of pain along the territory of the trigeminal nerve that did not fit into the classically known cranial neuralgias ( Fig. 1 ). This syndrome consisted of unilateral facial pain that lasted most of the day, was described as a severe ache, burning, or crushing sensation, and no autonomic abnormalities were noted. In fact, no abnormalities on examination or tests could be found. Today, this constellation of symptoms would fit into the diagnosis of persistent idiopathic facial pain (PIFP), or as it is more commonly called, atypical facial pain (AFP). AFP has an incidence of 1 in 100,000, affects mainly adults, and is equally distributed between men and women, although women present more commonly for treatment, with postmenopausal women being more frequent.

Algorithm for CIM treatment of chronic orofacial pain.

The etiology of PIFP remains unknown. At one point, it was believed to be psychogenic. Early reports of AFP suggested that more than two-thirds of patients had a comorbid psychiatric disorder. A role for female hormones was postulated, as more women present with this condition. Today, different neuropathic mechanisms are hypothesized to be responsible.

Physiology and anatomy

Sensation to the face is mediated by the trigeminal (Greek, “3 twins”) nerve. It provides somatic sensory afferents from the skin of the face, forehead, anterior scalp, and tympanic membrane, as well as the mucous membranes of the nasal cavity, paranasal sinuses, and oral cavity, including the anterior two-thirds of the tongue, conjunctivae, and the dura of the anterior and middle cranial fossae. In addition, it also contains special visceral efferents that provide motor function to the muscles of mastication (temporalis, masseter, medial and lateral pterygoids), tensor tympani, tensor veli palatini, mylohyoid, and anterior belly of the digastric.

The nerve arises from the midsurface of the pons in the brainstem and travels to Meckel cave, a cerebrospinal fluid–filled space over the petrous portion of the temporal bone. Here, sensory neuron cell bodies are found that comprise the trigeminal or semilunar/Gasserian ganglion on the floor of the middle cranial fossa. It is posterior, inferior, and lateral to the cavernous sinus. The ganglion contains fibers from all divisions of the nerve, the ophthalmic (V1), maxillary (V2), and mandibular (V3) roots. From there, the sensory fibers of the ganglion enter the pons to terminate into 3 major nuclear complexes within the brainstem. These nuclei are the main sensory nucleus of the trigeminal nerve, the mesencephalic nucleus of the trigeminal, and the spinal nucleus of the trigeminal, which is the largest. The spinal nucleus contains 3 subnuclei, 2 of which are important in pain processing: the subnucleus interpolaris, which is associated with the transmission of tactile sense and dental pain, and the subnucleus caudalis, which is associated with nociception and thermal sensation from the head. There is no parasympathetic nucleus of the nerve, or parasympathetic ganglia, although the trigeminal nerve is associated with the parasympathetic ganglia of other cranial nerves (oculomotor, facial, and glossopharyngeal).

The trigeminal system also includes 3 tracts. The spinal tract of the trigeminal nerve carries first-order sensory fibers responsible for pain, touch, and temperature from the orofacial area to the spinal nucleus of the trigeminal. The tract also contains first-order sensory afferents from the facial, glossopharyngeal, and vagus nerves, which terminate in the spinal trigeminal nucleus. By way of the reticular formation, the thalamus receives indirect trigeminal nociceptive input (dull, aching).

Half of the sensory fibers in the nerve are similar to the A (delta) and C (nociceptive) fibers found in the spinal nerves. Pain input is modulated in the nucleus by interneurons, and further processing occurs in the postcentral gyrus of the somatosensory cortex in the brain. Electrical stimulation of the midline periaqueductal gray matter, reticular nuclei, or medullary raphe nuclei, has an inhibitory effect on the nociceptive neurons. Substance P (a peptide found in the axon terminals of neurons involved in pain transmission) receptors and opiate receptors have been localized to the subnucleus caudalis, suggesting an endogenous opioid-mediated pain processing pathway, before integration into higher brain centers.

The sensations of light touch and pain/temperature are mediated by the trigeminal nerve. Lesions proximal or at the trigeminal ganglion cause sensory dysfunction over the entire ipsilateral face and forehead. Those distal to the ganglion result in sensory loss, pain, and dysesthesia/paresthesia confined to a single division. Notably, if there is a dissociation between touch and pain/temperature, this differentiates causes affecting the principal sensory nucleus from lesions affecting the solitary tract and nucleus of the trigeminal nerve. Some injuries may not produce complete loss of sensation, but decreased sensation (hypesthesia), altered sensation (dysesthesia), abnormal sensation (paresthesia), or pain in the affected division.

Transduction of painful stimuli occurs as a result of the interaction between molecules released after tissue injury (substance P, neuropeptide Y, histamine, bradykinin, glutamate, prostaglandins) and pain receptors located on free nerve endings. Peripheral sensitization of these free nerve endings produces increased excitability of the nerve, with spontaneous activity, a reduced activation threshold, and increased sensitivity to repeated stimulation. This may partly explain the findings of hyperalgesia, spontaneous pain, and allodynia in patients with chronic pain conditions. The altered activity of peripheral receptors may in turn cause functional alterations in central pain processing that further lead to chronic pain (“central sensitization”). Interestingly, recent research has uncovered gender differences in the peripheral molecular mechanisms of pain transduction, suggesting one reason why women may be predominantly affected in chronic pain conditions.

Symptoms

According to the International Headache Society’s 2004 classification, PIFP is “Persistent facial pain that does not have the characteristics of the cranial neuralgias described above ( Table 1 ) and is not attributed to another disorder.” The diagnosis therefore, is one of exclusion.

There are 4 criteria to be met for the diagnosis:

• 1.
  

  There is pain in the face present for most of the day or all day, and occurring daily.

  
  
• 2.
  

  Initially, the pain may be confined to a portion of the face, but is poorly localized and deep.

  
  
• 3.
  

  It is not associated with other physical signs or loss of sensation.

  
  
• 4.
  

  Workup in terms of imaging is unrevealing of an obvious anatomic or structural cause.

It may follow an operation or trauma to the face, teeth, or gums, but persists without a known local factor. Pain may start in the nasolabial crease or chin, and then spread to a wider region in the face and neck. One hypothesis for the etiology of the pain is a demyelination injury to the trigeminal nerve following trauma. In some cases, PIFP may be a precursor to trigeminal neuralgia, or the 2 may coexist and be difficult to differentiate. In a large population study out of Germany, the lifetime prevalence of PIFP was estimated to be 0.03%.

The key differential diagnoses are other causes of chronic orofacial pain, which may affect up to 10% of the adult population. This category includes temporomandibular joint disorders, atypical odontalgias, oral dysesthesias (including burning mouth syndrome), and atypical facial pain. The cranial neuralgias, listed in Table 1 , need to be considered, as does Eagle syndrome or stylohyoid complex syndrome, first bite syndrome, postherpetic neuralgia (pain that persists 1–6 months following a herpes zoster infection), headache/migraine, and rare neurologic entities, such as Raeder syndrome (trigeminal ophthalmic branch distribution of a unilateral burning pain that may be associated with miosis, ptosis, and hyperesthesia and can be caused by a middle fossa tumor, sinusitis, or syphilis), and thalamic pain syndrome (severe burning, aching unilateral facial pain that may be associated with dysethesias caused by a contralateral ventral-medial thalamic nuclei lesion). Neuralgia-inducing cavitational osteonecrosis has been hypothesized as a cause of chronic facial pain. Lung cancer may also lead to referred facial pain, and sometimes the onset of facial pain precedes the onset of symptoms and signs due to lung cancer by several months. Compression or invasion of the vagus nerve is implicated, and pain is usually temporal, along the ear or jaw, and described as a severe ache, either intermittent or continuous. Multiple sclerosis, a demyelinating disease, should also be considered.

In patients with trigeminal neuralgia, the pain is excruciating but short lasting, and localized to a branch of the trigeminal nerve. Patients are typically older. There may be triggers as well. The cause is believed to be ephaptic transmission of the nerve, or “short-circuiting,” from demyelination caused by nerve compression, such as from a vascular loop that envelops a nerve root. This is in contrast to trigeminal neuropathy, wherein injury to the trigeminal nerve, such as from facial trauma, dental trauma (most commonly), sinus trauma, or after destructive procedures (rhizotomies) used for treatment of trigeminal neuralgia is the root cause. Following injury, numbness may become associated with bothersome sensations or pain, sometimes called phantom pain or deafferentation pain. Pain is usually constant, aching, or burning, but may be worsened by exposure to triggers, such as wind and cold, and can start immediately or days to years following injury. The most extreme form, anesthesia dolorosa, presents with continuous severe pain in areas of complete numbness.

Medical treatment approaches and outcomes

The mainstay of medical treatment of PIFP is counseling. Patients should be counseled about the chronic nature of the illness, and its nonmalignant nature. Their pain should be acknowledged, and they should feel that their concerns are being heard, and a plan for addressing them is forthcoming. Toward this end, a comprehensive multidisciplinary team approach is most helpful. A short screening questionnaire for anxiety and/or depression (such as the Hospital Anxiety and Depression Scale ) or other surveys for common comorbidities in chronic pain may be administered, with appropriate referral to a psychologist/psychiatrist as necessary. A pain specialist may be able to initiate minimally invasive interventions, such as nerve blocks. Neurologists may be better able to manage the nuances of antiepileptic therapy trials.

Pharmacologic treatment