MAIN MILITARY MEDICAL DIRECTORATE

OF THE MINISTRY OF DEFENSE
OF THE RUSSIAN FEDERATION

MAIN MILITARY CLINICAL HOSPITAL
OF THE MINISTRY OF DEFENSE
OF THE RUSSIAN FEDERATION
LLC "AKELA-N"

The use of medical xenon in the treatment of headache and migraines

syndromes 

Xenon in the complex treatment and prevention of migraine

During a migraine attack the activation of trigeminal-vascular system and release of neuropeptides into the vessel wall occur, causing vessel dilation, increased wall permeability and, as a consequence, the development of neurogenic inflammation. Aseptic neurogenic inflammation activates the endings of the trigeminal nerve fibers, which transmit a pain impulse, leading to the formation of a pronounced pain syndrome at the level of the CNS [22].

The effectiveness of inhalations of xenon-oxygen mixture was studied in the treatment of 30 patients suffering from migraine.

Among all patients suffering from migraine, 24 patients had classic attacks of migraine with aura, and 6 patients had no any subjective sensations before cephalalgias. Disease duration ranged from 5 to 14 years. 11 patients had seasonal migraine attacks, up to 3-4 times a week, which occurred mainly in the autumn. Cyclical premenstrual migraine pain was observed in 12 female patients. All patients had to take analgesics during the period of the attack (from 2 to 4 tablets per day, including triptans and combination drugs).

Xenon inhalations were performed to relieve an emerging migraine attack and to prevent the occurrence of cyclic and seasonal hemicrania. The effectiveness of the prophylactic use of inhalations was assessed by the intensity of pain attacks (by visual analogue scale), the frequency of attacks, and the amount of used analgesics.

One inhalation lasting 20-40 min was enough to terminate the migraine attack. The concentration of xenon in the gas mixture and the duration of the procedure were selected individually and depended on the patient's subjective sensations (regression of headaches and vegetative manifestations). Almost all patients (28) a migraine attacks were terminated in about 3 to 4 minutes of inhalation, and there were no recurrences of headaches for the next 2-3 days. However, in 2 patients during inhalation, decrease in the intensity of the headache along with the development of severe vomiting, so the procedure had to be stopped approximately at the 4th-5th minute. Wherein, both patients noted a decrease in the intensity of cephalgic manifestations, the resumption of the efficacy of triptans and antiemetic drugs, which were non-effective before the inhalation.

It is most likely that inhaling xenon normalizes vascular tone and reduces neurogenic inflammation. The agonistic effect of inhalation on the brain receptors inhibits the release of neuropeptides from the central endings of the trigeminal nerve, reduces their excitation and blocks the conduction of pain.

In order to prevent the onset of migraine, 11 patients with seasonal migraines underwent a course of 4 inhalations with xenon-oxygen mixture. Procedures were performed every other day, the concentration of xenon in the gas mixture and the duration were selected individually (on average, 20-25 minutes with 15-20% xenon content).

It was possible to completely prevent the occurrence of seasonal pain (which occurred regularly before treatment) in 7 patients. Four patients reported a decrease in intensity and duration of attacks, as well as a reduction in the dose and frequency of analgesics.

We observed 12 female patients with periodic migraines that occurred several days before menstruation. Severe pain dramatically reduced their activity and performance for 3-4 days, with the need to take analgesics up to 3 times a day. The course of inhalation xenon-oxygen mixture consisted of 3 procedures performed every other day, and began a week before the onset of menstruation. The concentration of xenon was chosen individually and averaged 12-18%, with the duration of the procedure from 10 to 20 minutes. The use of xenon inhalations was able to prevent the occurrence of migraine cephalgia in 9 patients. In three patients, the attacks took place with less intensity and duration, with the need for only a single use of analgesics.

Thus, attacks can be terminated by xenon inhalations in combination with analgesics, NSAIDs, triptans, and as monotherapy also. Xenon inhalations can be very effective in preventing cephalgia in periodical and seasonal migraines.

Xenon in the complex treatment of tension headache and medication-overuse headache

Tension headache (THA) is the most frequent variant of a headache, which is noted in more than 50-80% of the population. Frequent episodic and especially chronic THA can significantly disrupt the vital activity of the patient. Mental disorders (anxiety, depression), pathology of the cervical spine and the temporomaxillary joint, as well as the abuse of analgesics, caffeine, benzodiazepines, barbiturates, ergotamine preparations, which lead to the occurrence of abuse and more severe course of pain syndrome, contribute to chronicity of headache.

The most effective treatment of THA is long-term use of antidepressants (from 4 to 6 months or more), but their use is limited due to frequent side effects, especially in elderly patients.

Medication-overuse headache (MOH) occurs when medications are used excessively. It manifests as a bilateral oppressive or squeezing cephalgia of mild to moderate intensity. Pain caused by abuse of painkillers (at least 15 days per month during three or more months) occurs almost every day.

Comorbid disorders, such as depression, dysthymia, panic attacks, anxiety, somatoform disorders, insomnia, and myofascial pain syndrome, commonly co-occur MOH. In addition to antidepressants, treatment of MOH involves withdrawal of the offending medication, pharmacological detoxification, and adequate alternative anesthesia.

The study was conducted to determine the effectiveness of inhalations of xenon-oxygen mixture in the treatment of THA (52 patients) and MOH (10 people).

Among all patients suffering from THA, 14patients had episodic pain, the rest of the patients had chronic THA. Disease duration ranged from 3 months to 4 years. 30 patients took different groups of analgesics regularly (2-8 tablets per day), 5 patients took them episodically. 17 patients took tetracyclic antidepressants (selective serotonin reuptake inhibitors) for 2-4 months with a small or inconsistent temporary effect.

Among patients with MOH, in 4 patients the disease was caused by a prolonged use of triptans for the previously diagnosed "migraine cephalgia", the rest of the patients took combined analgesics, including those containing opioids. The disease duration ranged from 6 months to 2 years.

Treatment by inhalation of xenon-oxygen gas mixture with xenon concentration maintained at the level of 20-35% was accompanied by gradual (patients with THA) or complete (in the case of MOH) withdrawal of analgesics with administration of minimal doses of antidepressants in combination with neuroprotective drugs for one to two months. Patients who had previously been prescribed antidepressant drugs continued to receive them in previous doses.

The effectiveness of treatment was assessed by the intensity of pain attacks (by visual analogue scale), the frequency of attacks, and the amount of used analgesics. The number of procedures depended on the disease duration, the persistence of the clinical manifestations of the disease and was 5-8 procedures for THA (average number - 6), 10-15 procedures for MOH (an average of 12 procedures). The duration of one inhalation was 15-40 minutes (an average of 25 min). The concentration of xenon in the gas mixture and the duration of the procedure were selected individually and were determined during the first "trial" procedure depending on the patient response to inhalation of the mixture. Inhalations were carried out for THA every other day or very two days, and for MOH every day or every other day.

The effect of the treatment in all patients with THA was observed after the first procedure. All patients with THA who had previously taken analgesics stopped taking them after the 3rd procedure; as a rule, the tension-type headache was terminated after the 5th-6th procedure. The subsequent duration of antidepressants treatment in the case of THA did not exceed 1 month.

Analysis of the catamnesis for 6-12 months has shown that THA did not recur in any of the patients. Additional inhalations of xenon-oxygen mixture (2-3 procedures) were needed for 6 patients with long-term (more than three months) intake of antidepressants because of the development of withdrawal syndrome on the background of a gradual reduction of the dose of antidepressants; this made it possible to completely abolish its manifestations.

A lasting positive effect was achieved in 5 patients with THA (complete refusal of medications that caused the disease) after the first course of inhalations of the mixture in combination with antidepressants. In two cases, a repeated course of treatment was carried out with the same positive effect. In three cases, it was possible to halve the dose of drugs (in two - combined analgesics containing opioids, and in one - triptans), whereas these patients initially had a lack of motivation for cure.

Thus, our experience shows the effectiveness of inhalations of xenon-oxygen mixture in the complex treatment of THA and MOH. In the latter case, xenon has become a drug that provides adequate alternative pain relief.

This method has significantly reduced the length of treatment of these categories of patients and the duration of intake of psychotropic drugs of various groups, long-term use of which, as a rule, causes adverse side effects. The important advantages of xenon, in contrast to traditional drug therapy, are a significant anxiolytic effect, improvement of cognitive functions, and preservation of the speed of attention.

Conclusion 

The study indicates a high therapeutic efficacy, safety and prospects of using XeMed® in the complex treatment of discogenic, vertebrogenic and neuropathic pain syndromes, as well as tension headaches, medication-overuse headaches and migraines. Xenon as a part of complex pharmaceutical programs leads to a significant reduction or complete relief of pain syndromes. There was also significant shortening treatment duration and reduction in the associated pharmacological load.

Xenon due to its effect on all the components of the mechanism of pain syndrome "breaks" the vicious pathological circle through blocking the pathological impulses, and thereby promotes normalization of microcirculation in tissues and metabolic processes, reduces swelling and musculo-tonic manifestations. In addition to the direct impact on conduction and perception of pain, xenon normalizes the psycho-emotional state of patients, reducing the emotional component of pain.

The inclusion of the course of inhalation procedures of therapeutic doses of xenon in the system of therapeutic, rehabilitation and preventive measures contributes to the rapid and effective relief of pain syndromes of various origins and creates additional motivation to undergo treatment.

The developed method allows to achieve maximum patient safety and comfort for the doctor due to the absence of complications of the procedure, maintenance of verbal contact with the patient and absence of agitation observed at high xenon concentrations.