J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.22.1.36 on 1 February 1959. Downloaded from J. Neurol. Neurosurg. Psychiat., 1959, 22, 36. THE MECHANISM OF THE PAIN IN TRIGEMINAL NEURALGIA- BY ERIC KUGELBERG and ULF LINDBLOM From the Department ofNeurology of the Karolinska Institute, Serafimerlasarettet, Stockholm, Sweden Trigeminal neuralgia (tic douloureux) is charac- with an intracranial arterial aneurysm. The remainder terized by brief paroxysms of pain limited to the had the common " cryptogenic" type. facial distribution of the trigeminal nerve and is At the beginning of the investigation the attacks were in the provoked by stroking the trigger zone with the finger tip precipitated by stimuli to sensory endings at, so far as possible, a constant rate, speed, and pressure. trigeminal receptive area. The condition is relieved Later, a vibratory stimulator was employed, consisting by blocking the afferent input of the trigeminal of a pin attached to the membrane of a loud-speaker nerve. According to Wyburn-Mason (1953) and which led to a Grass stimulator. The head of the pin, Crue, Shelden, Pudentz, and Freshwater (1956), which was a round knob, was pressed against the skin. attacks of trigeminal neuralgia can in some cases be The frequency and amplitude of the vibrations were abolished by interruption of adjacent cervical nerves. controlled with the stimulator which was switched on The neurophysiological mechanism underlying and off manually. The amplitude ranged from 0 to 1 mm. trigeminal neuralgia is still obscure (cf. List and and reached its maximum within 2 m.sec. This providedProtected by copyright. Williams, 1957). King and Meagher (1955), King a comparatively well-defined and reproducible mechanical and Barnett (1957), and King, Meagher, and stimulus of the skin. Barnett (1956) described alterations of trigeminal nerve potentials associated with over-reaction to Results tactile facial stimulation in cats produced by apply- Some patients have, during particularly severe ing alumina gel or strychnine to the spinal trige- periods of the disease, attacks of pain which minal nucleus. The electrical potential changes in apparently start spontaneously. They occur without the human trigeminal system associated with the tangible external irritation, such as touching the paroxysmal pain, however, remain to be investigated. face, talking, or eating, which is usually necessary Moreover, the finding of a correlation between the for precipitating an attack during less active periods. clinical syndrome of tic douloureux and the electro- The same patients may have periods of remission physiological phenomena presupposes a detailed when not even external stimuli will provoke an knowledge ofthe clinical events. Since the mechanism attack. It is also a well-known fact that the severity of the paroxysmal pain is intimately associated with of the disease can vary from day to day or from afferent discharges we have studied with semi- hour to hour. quantitative methods the relation between the Since even in patients with " spontaneous" attack of pain and stimuli applied to the skin attacks the pain is relieved by blocking the afferent http://jnnp.bmj.com/ trigger zone. The effect of anti-epileptic drugs, pathway of the fifth nerve, it may be assumed that such as hydantoin and lidocain, has also been inves- the pain is precipitated by afferent discharges and tigated. that deterioration or improvement reflects a lower- ing or raising of the attack threshold. During Material and Methods periods of " spontaneous ' attacks a minimum The present investigation was carried out on 50 patients stream of afferent impulses in the trigeminal nerve with trigeminal neuralgia who were admitted to the is evidently sufficient to provoke an attack. During Neurological Clinic during the years 1946 to 1957 and periods of improvement a higher intensity of afferent on October 2, 2021 by guest. in whom the attacks could be evoked by mechanical impulses is required, and during periods of remission stimulation of the trigeminal receptive area. A neces- the threshold is not reached even with a high sary requirement was that the patient had an observant mind and was willing to undergo repeated provocations intensity of afferent discharge. of the attacks. The rapid fluctuation in the severity of the One patient, an 18-year-old girl, suffered from symptoms indicates that the neurophysiological " symptomatic " trigeminal neuralgia associated with state responsible for the tic syndrome is very platybasia. In anotherpatient the neuralgia was associated unstable. Accordingly the quantitative relationship 36 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.22.1.36 on 1 February 1959. Downloaded from MECHANISM OF THE PAIN IN TRIGEMINAL NEURALGIA 37 right lef t FIG. 1.-Distribution of 31 trigger zones in 30 patients. Circles denote circumscribed and broken lines widespread, cutaneous trigger zones. Ovals indicate localization to alveolar gingiva. between the paroxysmal pain and the afferent trigger zone. For example, in one patient with the discharge may be expected to vary not only in trigger zone on the upper eyelid the pain started different individuals but also in the same individual in the cheek (cf. List and Williams, 1957). at different examinations as well as during the course of a prolonged examination. A basic pattern Adequate Stimulus.-It is common knowledge of the trigger mechanism, however, may be dis- that the attacks of pain are precipitated by tactile Protected by copyright. tinguished. stimulation of the trigger zone (e.g., touching the face, as in shaving or washing) or by stimuli such The Trigger Zone.-The site of the trigger zone as talking and mastication which increase the pro- in the last 30 patients examined is shown in Fig. 1. prioceptive inflow. Pain is a less effective stimulus. Although the trigger zone could be located almost In our patients severe pinching of the skin of the anywhere within the trigeminal receptive area it trigger zone with forceps failed to evoke an attack. was most common in the nasolabial fold, on the Thermal stimuli (a warm metal rod or cube of ice) upper lip, the lateral part of the lower lip, and the were ineffective when applied slowly, as was slowly- alveolar gingiva. Some patients had two trigger applied firm pressure. On the other hand, sudden zones and some reported that their trigger zone had application or release (off-effect) of pressure evoked shifted from one point to another during the course an attack in susceptible individuals. This suggests of the disease. One patient stated that she had a fairly rapid adaptation of the receptors responsible trigger zone outside the trigeminal area, located in for the paroxysmal pain. Stroking the skin with a the ipsilateral axilla. At the time of examination, blunt object, e.g., the finger of the examiner, was a however, it was not present, and therefore the highly effective stimulus. Firm stroking is perceived information is uncertain. Crue et al. (1956) reported as touch, light stroking as touch and tickle. Rapid a case of trigeminal neuralgia with a trigger zone displacement of a few hairs may also be effective. http://jnnp.bmj.com/ on the big toe. This is perceived as a tickle, with or without the In some of the patients the trigger zone was large component of touch. Slow displacement of the and diffuse but in the majority it was comparatively hair, however, or even a slow, steady, painful pull small and well-defined. How small the trigger zone on the hair failed to fire an attack. The vibratory can actually be is difficult to determine, but in some stimulus, causing a rapid distortion of the skin, of our patients it was not larger than 1 or 2 sq. mm. was effective in susceptible individuals. There was no obvious relationship between the Electrical stimulation was employed in an effort severity of the attack and the size of the trigger zone. to determine which fibres convey the effective im- on October 2, 2021 by guest. Very severe attacks could be fired in patients with pulses. In two patients with the trigger zone on the an almost punctate trigger zone as well as in those upper lip a needle electrode was inserted into the with a large trigger zone. The pain usually started infraorbital foramen. Repetitive weak shock stimuli near the trigger zone. Although it was rather to the maxillary nerve gave rise to the vibratory difficult for the patients to determine accurately the sensation typical of tactile fibre stimulation (cf. exact spot in which the pain actually started, it was Kugelberg, 1944), but did not evoke a paroxysm of obvious that the pain did not always start in the pain. An increase of the stimulus strength to J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.22.1.36 on 1 February 1959. Downloaded from 38 ERIC KUGELBERG AND ULF LINDBLOM threshold for the larger pain fibres still failed to pulse s/sec. provoke an attack. These results indicate either that G0 the fibres responsible for the paroxysmal pain have a smaller diameter and a higher threshold than the large pain fibres or possibly that the spatial and 45 temporal pattern of the triggering discharge is too specific to be imitated by electrical shock stimulation of the nerve. Shock stimulation did not appear to have an inhibitory action since the attack could 30 still be triggered from the upper lip during the electrical stimulation. \_0 1 5 Eliciting the Attack of Pain.-Four factors are discussed. three patients (1) Minimal Afferent Discharge.-In 1 1 5 sec. it was possible to trigger an attack by rapid dis- 5 0 placement of a single hair. In susceptible individuals FIG. 3.-Summation time (abscissa) in relation to vibration frequency evidently only a minimum number of nerve fibres (ordinate). to the critical are required to convey impulses measure the structure to fire an attack.