KR20110066460A - Deep brain stimulation device for pain treatment and method for pain treatment using the device - Google Patents

Abstract

PURPOSE: A deep brain stimulation device for pain treatment and a method thereof are provided to treat pain using a bipolar electrode needle and an electrostimulation generator. CONSTITUTION: A deep brain stimulation device for pain treatment comprises: one or more bipolar electrode needle which is inserted through the skull in order to contact a domain of the brain controlling pain; and an electrostimulation generator which is connected to the electrode needle and generates electrostimulation. The domain of the brain controlling pain is ventral posteromedial nucleus and ventral posterolateral nucleus.

Description

Deep brain stimulation device for pain treatment and method for pain treatment using the device

The present invention relates to an apparatus and method that can alleviate intractable pain through deep brain stimulation of the thalamus, including chronic pain, inflammatory pain, neuropathic pain, etc., which are difficult to control with conventional drug treatment.

Conventional pain has been mainly treated with drugs, but the pain treatment using drugs as described above may cause frequent drug side effects and resistance to drugs due to long-term medications such as chronic pain. Drugs can lead to conditions that have no effect on pain relief.

On the other hand, 'electric stimulation therapy' that is known to try to cure by inserting an electric wire into the heart or brain and flowing minute electricity, also known as 'deep stimulation'. Representatively, patients with arrhythmias are known to be able to supply electricity by planting electrical stimulators around the heart, and heart stimulation has been attempted to treat brain diseases.

For example, a small hole in the brain of a Parkinson's disease patient can be inserted into the hypothalamus nucleus by inserting an electric wire into the hypothalamus nucleus. . In addition, myotonic dystrophy, which is a disease in which the neck and legs are twisted by repeatedly shaking the neck and legs, is caused by damage to the 'bile lancet' in the core of the brain and excitement of surrounding cell activity. In this case, electrical stimulation may be applied to the gall bladder region to calm and treat abnormal cell activity.

Other diseases known to be applicable to deep brain stimulation generally include hydrocephalus, depression, obsessive compulsive disorder, epilepsy, and deep brain stimulation has been attempted in the treatment of obesity. Deep brain stimulation is known to have a good effect on afferent blockage pain mainly in peripheral nerve disease or partial spinal cord injury. On the other hand, in the case of thalamic syndrome, anesthesia or complete spinal cord injury, it is difficult to expect a good effect.

The areas of the brain where deep brain stimulation takes place can be divided mainly into two types, one of which is around the hydrocephalus or the periventricular gray matter, and the other is the ventral posterior medial / abdominal posterior / thalamic sensory nucleus or endothelial posterior margin. to be. In case of deep brain stimulation, it is planted in electrodes by multi-contact stereotactic brain surgery under an image amplification device. Conventionally, the location was confirmed by ventricular angiography, but recently, a target place has been found using CT or MRI.

In relation to pain, there have been cases where deep brain stimulation has been attempted in the treatment of pain relief that is difficult to fix, but the pain transmission mechanism in the brain is not understood correctly, so the individual difference in the treatment effect was large in each patient. Stimulation of periaqueductal gray caused the development of resistance.

Therefore, there is no fear of side effects or resistance in the treatment of pain as in conventional drug treatment, and there is a need for an apparatus and method for treating pain by effective brain deep stimulation.

One aspect of the present invention is to provide a device that can effectively relieve pain through deep brain stimulation.

Another aspect of the present invention is to provide a method for alleviating pain by using a deep brain stimulation device.

According to one aspect of the invention, at least one bipolar electrode needle implanted through the skull so as to contact the region of the brain for controlling pain, an electrical stimulation generator connected to the electrode needle and generating an electrical stimulation Provided is a deep brain stimulation device for treating pain.

According to another aspect of the invention, implanting a bipolar electrode needle connected to the electrical stimulation generating device for generating an electrical stimulation in the region of the brain that controls the pain of the patient and imparting electrical stimulation through the electrode needle Provided is a method for treating pain by deep brain stimulation comprising a step.

The region of the brain that controls the pain is preferably the ventral posteromedial nucleus (VPM) and the ventral posterolateral nucleus (VPL).

The electrical stimulation produces a burst of 0.05-10 seconds (sec) of two to ten pulses with a pulse intensity of 50-1000 μA, a pulse duration of 50-500 μs, and a pulse interval of 1-15 milliseconds (msec). It is preferable to generate a burst with a gap between them.

The pain is preferably chronic pain, inflammatory pain, neuropathic pain.

The patient may be a mammal, including mammals other than humans.

According to the deep brain stimulation device of the present invention and the pain treatment method using the same, by giving an electrical stimulation mimics the method used when nerve cells block signal transmission to the thalamus (VPM / VPL) part responsible for pain transmission in the brain, There is no concern about the side effects or tolerances associated with conventional drug treatments, and pain relief can be effectively used by using a method that essentially blocks pain signaling.

The deep brain stimulation device according to the present invention directly stimulates the thalamus nucleus responsible for pain delivery in the brain before pain is perceived. The painful part of the brain is the cerebral cortex, and pain signals are transmitted to the cerebral cortex through the thalamus. On the other hand, the control of the pain signal to the cerebral cortex in the cerebral cortex, nuclei of reticular thalamus (NRT), ventral posteromedial nucleus (VPM) and ventral posterolateral nucleus (VPL) ) Is made of interaction.

The deep brain stimulation device of the present invention imparts electrical stimulation to the region of the brain that controls pain, and the region of the brain that controls the pain is ventral posterior medial nucleus (VPM) and ventral posterior lateral nucleus (VPM). ventral posterolateral nucleus (VPL).

Figure 1 shows the ventral posteromedial nucleus (VPM) and ventral posterolateral nucleus (VPL) locations of the brain associated with pain response in humans, Figure 1 (a) is a three-dimensional brain structure 1 (b) shows a schematic cross section, and the target position is an area indicated by a circle. FIG. 2 is a schematic representation of the location of ventral posteromedial nucleus (VPM) and ventral posterolateral nucleus (VPL) associated with pain response in rodents. FIG. .

The deep brain stimulation device of the present invention includes at least one bipolar electrode needle inserted through the skull so as to contact the region of the brain for controlling pain and an electrical stimulation generator connected to the electrode needle and generating electrical stimulation. 3 is a schematic illustration of a device according to the invention, comprising an electric stimulation generating device 30 and an electrode needle 10 for generating an electrical stimulation, which are connected by a cable 20 have.

The bipolar electrode needle includes both the cathode needle and the anode needle, which is inserted into the thalamus of the brain and contacts the deep brain nerve. The material effectively transmits electrical stimulation and does not react to fluids in the human body and has no rejection reaction. It is preferably composed of, and particularly preferably composed of a biocompatible material (physiologically adaptable to the human body). For example, gold, stainless steel, tungsten and the like can be used. The electrode needle may be formed in the form of a needle to a needle, these surfaces are preferably configured to stimulate only the brain area is coated with an insulation except for the tip of the electrode needle. On the other hand, the material that can be used for the insulation may be any material known in the art as insulating and harmless to the human body, such as polyimide (polyimide).

The number of electrode needles inserted into the patient may vary depending on the patient, in particular, the size of the brain region requiring electrical stimulation. That is, the electrode needle may be one to a plurality, for example, may be one to five. On the other hand, if the brain area is large depending on the patient, it is preferable to use a plurality of electrode needles to uniformly give the effect of the electrical stimulation to the target area, the electrode insertion surgery time is more than five electrode needles It can be long, and the prognosis can be poor. However, this may be appropriately changed according to the size of the patient and the brain, and the number is not limited thereto.

The electrode needle is a portion inserted into the brain for deep brain stimulation, it is preferable to be fixed from the outside of the skull. The electrode needle is connected to a generator that generates electrical stimulation. At this time, the electrode needle may be connected to the electrical stimulation generating device through a cable 20 as shown in FIG.

On the other hand, the deep brain stimulation device of the present invention in another aspect, as shown in Figure 4 power supply 40 for supplying power, the electrical stimulation generating device 50 for generating electrical stimulation and the region of the brain to control pain It may be configured to include at least one bipolar electrode needle 10 that is implanted through the skull to be in contact with and implanted in the brain. The deep brain stimulation device according to one aspect of the present invention shown in FIG. 4 integrates the device of FIG. 3, that is, a model in which the electrical stimulation generating device and the electrode needle are combined and do not need a cable connecting the two parts. to be. The device of FIG. 4 may include a power supply 40 for supplying power, which may be a battery.

Electrostimulation generators that can be used in the present invention are preferably capable of generating electrical stimulation having a pulse intensity of 50-1000 μA, a pulse duration of 50-500 μs, and a pulse interval of 1-15 milliseconds (msec). . Pulse intensities of less than 50 μA are insufficient to impart a pain therapeutic effect, and in the case of pulse intensities exceeding 1000 μA, cellular tissue may be damaged. On the other hand, if the pulse duration is less than 50 μs is insufficient to impart a pain treatment effect, if it exceeds 500 μs there is a fear that the cell tissue is damaged.

During or after the excitation process of nerve cells, there is an absolute non-resonance of nerve cells, which is a time when no strong stimulus is generated, so the stimulation is less than 1 millisecond pulse interval. Giving is not effective, and when the pulse interval exceeds 15 milliseconds (msec), it does not correspond to a burst, a signaling system used by the cells of the thalamus to block pain transmission.

Burst is one of the signaling mechanisms of sagittal cells that generate two or more pulses within a short time. Two pulses are the smallest unit of burst and two to ten pulses occur naturally. After the burst, a pulse-free rest period follows, and the rest period is an important feature of the burst. If there is no rest period, it is not recognized as a burst. Therefore, the interval between bursts, that is, the resting period is preferably 0.05 seconds (sec) or more.

In the present invention, one burst includes two to ten pulses, and ten or more pulses may be included in one burst, but this type of burst rarely occurs naturally. The burst is preferably provided with an interval between bursts of 0.05-10 seconds (sec). If the interval between bursts is less than 0.05 seconds, there is a possibility that burst recognition, which is the signaling system used by the cells of the thalamus to block pain transmission, may not be recognized, and the number of bursts and the degree of pain are proportional, so if the interval between bursts exceeds 10 seconds, In proportion, the pain reduction effect may be reduced.

As used herein, the term “pain” may be defined as an unpleasant sensory and emotional experience accompanied by or manifested in substantial and potential tissue damage, or both, with pain typically being location, duration, cause, frequency, and intensity. Are classified in several ways.

Pain to which the brain deep stimulation apparatus of the present invention can be applied may be intractable pain including chronic pain, inflammatory pain, neuropathic pain, and the like.

Pain associated with inflammatory diseases include chronic inflammatory diseases of the joints including arthritis, rheumatoid arthritis, osteoarthritis and bone diseases associated with increased bone resorption; Inflammatory lung diseases such as asthma, adult respiratory distress syndrome and chronic obstructive airway disease; Inflammatory eye diseases including trachoma, uveitis, sympathetic ophthalmitis and ophthalmitis; Chronic inflammatory diseases of the gums, including gingivitis and periodontitis; Tuberculosis; leprosy; Inflammatory kidney disease, including uremia complications, glomerulonephritis and nephropathy; Inflammatory central nervous system diseases including chronic demyelinating diseases of the nervous system, AIDS-related neurodegeneration, infectious meningitis, encephalomyelitis, and viral or autoimmune encephalitis; Autoimmune diseases, including type I and type II diabetes; Diabetic nephropathy (such as microalbuminuria and progressive diabetes nephropathy), polyneuropathy, mononeuropathy, autonomic neuropathy, atherosclerotic coronary artery disease, peripheral arterial disease, biketone hyperglycemia-gosmol coma, foot ulcers, Joint complications and skin or mucosal complications (such as, but not limited to, infections, shin spots, Candida infections or diabetic milk fat bionecrosis); Immune-complex vasculitis and systemic lupus erythematosus (SLE); Inflammatory heart disease such as cardiomyopathy; Refractory pain caused by pre-eclampsia, chronic liver failure, brain and spinal cord trauma, and cancer and several other diseases with significant inflammatory components.

Neuropathic pain includes, but is not limited to, neuropathy and idiopathic pain syndromes and neuropathies, such as pain associated with diabetic neuropathy, burning pain, palsy nerve tearing, laryngeal pain, fibromyalgia, gout and other forms of neuralgia.

Organs, including but not limited to headache, eye pain, corneal pain, bone pain, heart pain, skin / burn pain, lung pain, visceral pain (kidney, gallbladder, etc.), joint pain, toothache, muscle pain, and pelvic pain Or any pain that appears in chronic form even in tissue pain and pain accompanied by, but not limited to, pain associated with cancer, AIDS, arthritis, herpes and migraine headaches.

In another aspect of the present invention, implanting a bipolar electrode needle connected to the electrical stimulation generating device for generating electrical stimulation in the region of the brain that controls the pain of the patient in the patient and imparts electrical stimulation through the electrode needle Provided is a method for treating pain by deep brain stimulation, including the steps of: In the present invention, the patient may be a mammal including a human, a rat, and the like, but is not particularly limited, but the patient may be a mammal except a human.

The regions of the brain that control pain are the ventral posteromedial nucleus (VPM) and the ventral posterolateral nucleus (VPL), and the ventral posterior medial nucleus, the target location of the device. The posteromedial thalamic nucleus and the ventral posterolateral thalamic nucleus are known to regulate signals from the sensory organs as intermediate pathways through the body and face sensations, including pain, before pain is detected in the cerebral cortex.

As described above, two to ten pulses with a pulse intensity of 50-1000 μA, a pulse duration of 50-500 μs, and a pulse interval of 1-15 milliseconds (msec) are placed in the brain core at 0.05-10 seconds ( The pain can be treated by electrical stimulation in the form of a burst with a gap between bursts of sec). As shown in Example and FIG. 6, the mice that received the electrical stimulation using the deep brain stimulation device of the present invention were able to confirm that the pain response was significantly reduced compared to the mice that did not.

The pain to which the method of the present invention may be applied may be, but is not limited to, chronic pain, inflammatory pain, and neuropathic pain described above.

Hereinafter, the present invention will be described in more detail with reference to specific examples, and the following examples are provided to more specifically describe the present invention, and the present invention is not limited by the following examples.

Example

1. Preparation of a deep brain stimulation device according to the present invention

The deep brain stimulation device according to the present invention includes an electrode needle 10 inserted into the thalamus of the brain as shown in FIG. 3, an electrical stimulator 30 and an electrode needle 10 for generating an electrical stimulation, and It is composed of a cable 20 connecting the electric stimulation generating device (30). In this embodiment, the electrode was made of stainless steel.

2. Pain control experiment using deep brain stimulation device

(1) Preparation of Inflammatory Pain Model

Two to five 8-14 week old mice are kept per cage for 12-hour light-dark cycles (light starts at 8 am), keeping food at 22-25 degrees Celsius and freely feeding food. It was. To induce inflammatory pain, the mice were infused with 5% formalin in the rear paws and the pain was measured by the length of time they lick, bite or float the formalin injection. In the pain-induced mouse model as described above, tissue damage is caused to induce persistent pain. The mouse model thus prepared is inflamed at the formalin injection site and feel inflammatory pain.

(2) Insertion of deep brain stimulation device according to the present invention

A small opening is made in the skull of the experimental animal model prepared in (1), and the deep brain stimulator is placed in the thalamus (VPM / VPL) associated with pain. The position of the target was calculated by a stereotaxic instrument, and then an electrode was inserted into the calculated target position. It was then fixed with dental cement.

(3) pain control effect of the deep brain stimulation device according to the present invention

In order to examine the pain control effect of the deep brain stimulation device of the present invention in the mouse inserted the deep brain stimulation device of the present invention according to (2), immediately after formalin injection of the experimental animal model prepared in the above (1) Electrical stimulation was given to the thalamus (VPM / VPL). That is, inflammatory pain caused by formalin occurred about 15 minutes after injection, and electrical stimulation was given when the primary pain occurred when the needle penetrated the epidermis. On the other hand, the degree of pain response was also measured in the mice that were not given electrical stimulation because the device of the present invention was not inserted as a control.

Brain stimulation given in this experiment was applied for 60 minutes of pain duration as electrical stimulation with 333Hz burst frequency, 600 ms burst interval, and 100μA intensity.

In this experiment, the degree of pain response was measured by observing the behavior of licking, biting, and shaking duration. These behaviors can be regarded as spontaneous pain response, and the pain response was calculated by adding up the licking period, the waking period, and the shaking period. In other words, the pain level was analyzed at 5 minute intervals during the 1-hour experiment, and the sum of the actions of licking, biting, or shaking during each 5 minute interval, such as 0-5 minutes and 5-10 minutes, after formalin injection. As pain response. The average value between the mice was calculated after measuring as described above for each mouse. In the control group, the average value was obtained after observing the response of 9 mice, and in the experimental group, the average value was obtained after observing the response of 6 mice.

As a result, as shown in FIG. 6, the mice that received the electrical stimulation using the deep brain stimulation device of the present invention were able to confirm that the pain response was significantly reduced compared to the mice that did not.

In the graph shown in FIG. 6, the x-axis represents the time course after the pain induction, and the pain level was measured for 1 hour for each mouse, and then the average of the pain level measurement values for each 5 minute period was shown. The longer the duration of licking, biting, and shaking in the graph, the greater the pain response.

1 shows the location of the thalamus of the brain associated with pain response in humans.

Figure 2 shows the location of the thalamus of the brain associated with pain response in rodents.

Figure 3 illustrates a deep brain stimulation device according to an embodiment of the present invention.

Figure 4 illustrates a deep brain stimulation device for implantation according to another embodiment of the present invention.

Figure 5 illustrates the waveform of the electrical stimulation output signal of the deep brain stimulation device that can be used in the present invention for the treatment of pain.

Figure 6 shows a graph comparing the pain response of the mouse and the control group that gave the electrical stimulation using the deep brain stimulation device of the present invention.

Claims (9)

Deep brain for pain treatment comprising at least one bipolar electrode needle inserted through the skull so as to contact a region of the brain for controlling pain, and an electrical stimulation generator connected to the electrode needle to generate electrical stimulation Stimulation device. The deep brain stimulation device for pain treatment according to claim 1, wherein the pain-controlling brain regions are ventral posteromedial nucleus (VPM) and ventral posterolateral nucleus (VPL). The method of claim 1, wherein the electrical stimulation is 0.05-10 for two to ten pulses having a pulse intensity of 50-1000 μA, pulse duration of 50-500 μs, pulse interval of 1-15 milliseconds (msec). A deep brain stimulation device for pain treatment caused by a burst having an interval between seconds and bursts. The deep brain stimulation device according to claim 1, wherein the pain is chronic pain, inflammatory pain, neuropathic pain. Inserting a bipolar electrode needle connected to the electrical stimulation generating device for generating an electrical stimulation in the region of the brain for controlling the pain of the patient and imparting electrical stimulation through the electrode needle to the deep brain stimulation Pain treatment method. The method of claim 5, wherein the patient is a mammal other than a human. The method of claim 5, wherein the region of the brain that controls pain is ventral posteromedial nucleus (VPM) and ventral posterolateral nucleus (VPL). The method of claim 5, wherein the electrical stimulation is 0.05-10 pulses of 10 to 10 pulses having a pulse intensity of 50-1000 μA, pulse duration of 50-500 μs, pulse interval of 1-15 milliseconds (msec). A method for treating pain by deep brain stimulation caused by a burst having a gap between bursts of seconds. The method of claim 5, wherein the pain is chronic pain, inflammatory pain, neuropathic pain.

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