Pain can not only be a symptom of a disease, but in fact some pain is a disease in itself, such as central pain, phantom limb pain and other neuropathic pain, which has been a clinical treatment challenge and seriously affects the quality of life and health status of patients. With social progress and economic development, the treatment of pain has also received more and more attention, and there is an urgent need for safe and effective treatments to eliminate pain. Internationally, as early as 100 years ago, pain has been included in the scope of neurosurgery, and neurosurgical pain surgery has experienced several ebbs and flows in its history, until the last two or three decades, it has really been more widely recognized and applied. More than a decade ago, a few large functional neurosurgery centers in China, such as Beijing and Shanghai, also began to focus on the surgical treatment of pain research, successively carried out a variety of neurosurgical pain surgery, and achieved promising clinical results. In fact, neurosurgical analgesic surgery is mainly performed for intractable neuropathic pain, of which the most common indication is central pain [1]. Yongsheng Hu, Department of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University
1 Clinical characteristics of central pain
Central pain refers to pain caused by central nervous system lesions or dysfunctions, with primary lesions in the spinal cord or brain, and common etiologies include hemorrhage, infarction, vascular malformation, tumor, trauma, infection, multiple sclerosis, neuronal degeneration, and spinal cavernous disease. In a broad sense, the pain of Parkinson’s disease, even trigeminal neuralgia and glossopharyngeal neuralgia caused by vascular compression of the cranial nerve roots into the medullary region should also be classified as central pain.
Central pain is secondary to a lesion or dysfunction of the central nervous system and may appear immediately or months or years later, most occurring within a few months. The pain is most often located in a somatic area with hyperalgesia, sensory loss, or sensory abnormalities, and can be localized, throughout the limbs, half of the body, or head and face. Burning pain is the most common type of pain, and other pains such as slashing, stabbing, tearing, crushing, and tightening pains, as well as pulling pains, vague pains, and throbbing pains, can be present either alone or in combination. Clinical pain can be of any nature and in any form, and can be high or low in intensity. Various internal or external stimuli, such as touching objects, cold, and mood swings, can often trigger or aggravate pain.
Most of the central pain persists and worsens in paroxysms. The duration of the disease is prolonged and progressive. It is often accompanied by other manifestations of central nervous system lesions, such as headache, hemiplegia, paraplegia, monoplegia, aphasia, ataxia, cranial nerve damage, somatic sensory disorders, and urinary and fecal dysfunction.
At present, there is no universal effective treatment for central pain. Due to the limited efficacy of analgesic drugs and nerve blocks, neurosurgical analgesic procedures are often the mainstay, and combined application of multiple therapies can sometimes achieve better results [2].
2 Common types of central pain
2.1 Central post-stroke pain Central post-stroke pain (CPSP) is the most common type of central pain and can be caused by various cerebrovascular lesions, with an incidence of about 8%. Due to the large number of patients with cerebrovascular disease, the number of CPSP cases is considerable. Stroke is divided into hemorrhage and infarction, and probably because infarction is more common, CPSP caused by infarction is a little more frequent in clinical practice. The size of the stroke extent is not the key to cause CPSP, but the more important factor is the site of stroke. The common sites that can cause CPSP include: dorsolateral medulla, thalamus, posterior limb of the internal capsule, and the cortex or subcortex of the postcentral gyrus, with dorsolateral medulla and thalamus being the most common [3,4].
The extent of CPSP is generally large, often involving half of the body, half of the trunk, or half of the head and face, and the vast majority are accompanied by other positive neurological signs and symptoms, such as abnormal sensation, limb paralysis, ataxia, swallowing and choking, hoarseness, diplopia, aphasia, and positive pyramidal fasciculus signs [3,4].
2.2 Pain after spinal cord injury Pain after spinal cord injury (SCIP) is one of the common consequences of spinal cord injury, occurring in as many as 2/3 to 3/4 of patients. In addition to motor dysfunction and sphincter dysfunction, SCIP is often the greatest annoyance and pain. whether SCIP occurs and the severity may be related to a variety of factors, such as the cause of injury, segmentation, severity, etc. It is generally believed that mechanical injuries and gunshot wounds have a greater chance of causing SCIP. The International Society for the Study of Pain divides SCIP into two major categories, injury-receptive pain and neuropathic pain; further subdivided into five types, injury-receptive pain is divided into musculoskeletal pain and visceral pain; neuropathic pain is divided into pain above the plane of injury, pain in the plane of injury, and pain below the plane of injury [5]. It is mainly the latter two types that require neurosurgical treatment [6].
SCIP at the plane of injury is mostly sharp, severe electric shock-like, gunshot-like, burning, knife-like, or pinprick-like pain, sometimes combined with fasciculation-like sensory abnormalities, distributed in the segmental area corresponding to the plane of injury, generally not exceeding the upper and lower 2 spinal cord segments, commonly in patients with spinal nerve root or plexus avulsions. SCIP below the injury plane is located in part or all of the area below the injury plane, and is often accompanied by central hyperalgesia, phantom limb pain or de-afferent pain, which mostly appears very early after spinal cord injury, mostly burning-like, knife-like pain, often accompanied by sensory hypersensitivity; both complete and incomplete spinal cord injury can cause this pain.
3 Commonly used neurosurgical pain relief surgery
The basic principle of neurosurgical pain relief surgery is to block the conduction at a certain level of the pain transmission pathway, or to reduce the abnormal excitation of the relevant nuclei and cerebral cortex, so as to interfere with or inhibit the modulation and formation of pain, thus achieving the effect of relieving or eliminating pain. The first posterior spinal nerve root dissection was performed in 1889, more than 120 years ago. Since then, there have been various procedures such as anterolateral spinal cord bundle dissection, anterior joint spinal cord dissection, thalamic nucleus destruction, cingulate gyrus dissection, frontal corticotomy, and inferior frontal fiber bundle dissection, etc., which have been used to varying degrees. However, due to the long-term efficacy and complications, these procedures have gradually been carried out less and less internationally, and the actual number of cases carried out in China is also small.
In fact, the most widely used and satisfactory neurosurgical pain relief procedures in China and abroad are cranial nerve root microvascular decompression for trigeminal neuralgia and glossopharyngeal neuralgia, and many scholars have treated these two pains as special types. In addition, the main neurosurgical pain relief procedures that have been reported more frequently and have gained increasing attention and recognition internationally in recent years are as follows.
3.1 Dorsal root entry zone (DREZ) incision The dorsal root entry zone (DREZ) incision was started in the 1970s. By destroying the Rexed I-IV laminae in the dorsal horn of the spinal cord, the secondary neurons of nociceptive transmission (dorsal horn neurons) can be destroyed, and the thalamic tract and spinal reticular tract of the spinal cord can be partially destroyed to reduce the transmission of pain impulses. thus eliminating pain. It can effectively treat pain after spinal nerve root avulsion injury, SCIP, phantom limb pain, amputation pain, and post-herpetic infection neuralgia, etc. The analgesic effect is strong and long-lasting enough, and the long-term efficiency reported in domestic and international literature is over 80% [7-9].
Some scholars used spinal cord surface electrodes to monitor the field potential of spinal cord dorsal horn neurons during DREZ dissection in patients with post-avulsion pain and SCIP of the brachial plexus nerve roots, and abnormal active spontaneous discharges with repeated intermittent high-frequency, high-amplitude, burst-like discharges could be recorded; the abnormal discharges disappeared after DREZ dissection. This suggests that the abnormally active spontaneous discharges present in the neurons of the dorsal horn of the spinal cord are likely to be related to the occurrence of pain [10].DREZ dissection has been used more frequently abroad and has become the procedure of choice for the treatment of post-avulsion pain and SCIP in the brachial plexus nerve roots, but it has not been carried out widely in China, and is currently being practically applied only in individual larger functional neurosurgery centers in Beijing and Shanghai [11].
3.2 Stereotactic midbrain plus cingulate gyrus dissection After the 1980s, with the development of neuroimaging, stereotactic technology and microelectrode recording technology, the accuracy of intracerebral target localization was greatly improved, and the accuracy and safety of midbrain dissection were greatly improved and complications were significantly reduced, thus regaining the attention of scholars. The spinal thalamus and trigeminal tracts of the midbrain are the most concentrated sites in the brain before nociceptive transmission from the soma and head and face reaches the thalamus, respectively, and can be more completely blocked with smaller disruption foci. The cingulate gyrus is anatomically linked to the striatum, anterior thalamus, hippocampus, limbic system, and frontal cortex and plays an important role in the control of mental states and emotional responses. After disruption of the cingulate gyrus, the patient’s symptoms of anxiety, depression, and obsessions are improved and pain is significantly relieved.
However, the long-term efficacy of destroying only one side of the midbrain or bilateral anterior cingulate gyrus is unstable, while the long-term pain relief of combined destruction of the midbrain plus bilateral anterior cingulate gyrus is more satisfactory. It is generally believed that there are two main pathways of pain: somatosensory and emotional responses, and destruction of the conduction bundle of the midbrain on one side can block the somatosensory pathway on the opposite side, while destruction of the anterior part of the cingulate gyrus on both sides can block the emotional response pathway, and if the midbrain and anterior part of the cingulate gyrus are combined, both pathways can be blocked at the same time, and thus more definite and long-lasting pain relief will be obtained [12,13].
3.3 Neuroelectrical stimulation Neuroelectrical stimulation is a widely recognized and respected neurosurgical pain relief procedure in the last decade or so. It uses implanted stimulation electrodes and permanent pulse generators to modulate the conduction, presentation, and formation of pain through chronic electrical stimulation to achieve pain relief or elimination. Depending on the site of stimulation, it can be divided into peripheral nerve stimulation (PNS), spinal cord stimulation (SCS), deep brain stimulation (DBS), and motor cortex stimulation (MCS). SCS is mainly used for failed back surgery syndrome.
SCS is mainly used for failed back surgery syndrome (FBSS), complex regional pain syndrome (CRPS), postherpetic pain, post-peripheral nerve injury pain, limb ischemic pain, and angina pectoris [14]. DBS and MCS are indicated for various central pains, de-afferent pains, etc. [15]. Among them, SCS and MCS have more definite and stable pain relief effects.
Neuroelectrical stimulation has the advantages of being less invasive, programmable, testable, and reversible, and has been widely used in pain neurosurgical treatment in developed countries in Europe and the United States, and even some of them have become the preferred procedure. In China, the more expensive cost has limited its widespread clinical application to a certain extent, and only a few cities such as Beijing, Shanghai, and Shenzhen are currently carrying out the procedure, but the technical advantages and application prospects of nerve electrical stimulation are undoubted.
4 Problems and countermeasures
Although the clinical application of neurosurgical analgesic surgery is being paid more and more attention, there are still some problems facing how to carry out and promote it scientifically, safely and effectively.
First, the indications for various neurosurgical analgesic procedures need to be further clarified and refined, and it is possible that different types of pain need to be treated with different procedures in order to obtain better efficacy. For example, CPSP is suitable for treatment with MCS, while SCIP is more effective with DREZ incision. In the same case of CPSP, if there is complete limb paralysis and significant brain atrophy, the outcome of MCS may not be too satisfactory. In the same case of SCIP, if sensation is still present, SCS should be effective; if sensation is completely absent, I am afraid that only DREZ incision can be effective. These experiences and inferences need to be confirmed and corrected by the results of long-term clinical studies of large number of surgical cases.
Secondly, the successful implementation of neurosurgical pain relief surgery does not only rely on microsurgery and stereotactic techniques, but also requires more complete and advanced neurophysiological monitoring techniques to “escort”. The application of various intraoperative electrophysiological monitoring techniques, such as sensory evoked potentials, motor evoked potentials, electromyography, cortical electrograms, spinal electrograms, cortical stimulation, spinal cord stimulation, and nerve microelectrode recordings, can improve both the safety and the effectiveness of the surgery. Obviously, this limits the application of such procedures in the short term, which may only be suitable for larger functional neurosurgery centers where objective conditions are not complete, and should not be carried out hastily.
Third, pain relief surgery is not the only treatment, but often requires a combination of methods, especially pharmacotherapy and psychotherapy should be given sufficient attention. Some trans-surgical pain relief surgeries may not be able to completely eliminate pain, but may only partially relieve or control pain, at which time it is necessary to continue taking analgesic, anti-epileptic, anti-depressant or anti-anxiety drugs according to the patient’s specific condition, together with appropriate psychotherapy, all of which can consolidate and improve the efficacy of surgery.
Finally, a problem that should not be overlooked is the serious lack of specialized physician training and pain patient education. Neurosurgeons mainly face a large number of patients with tumor, trauma, and vascular disease in their daily work, and there is a relative lack of understanding of theoretical knowledge and surgical skills in functional neurosurgery, especially in pain, which undoubtedly limits the in-depth development of neurosurgical pain relief surgery. On the other hand, neurosurgeons often do not directly face many pain patients, and patients with central pain who really need and must be treated with neurosurgical pain relief surgery to effectively control their pain should have a smooth channel to obtain relevant knowledge and recommendations, which requires both strengthening health education for patients and all pain management physicians to be aware of this, and most importantly, should The most important thing is to strengthen multi-specialty and multidisciplinary complementarity and collaboration in pain management.
5 Outlook
The development of pain medicine at home and abroad is still on the rise, and the application of neurosurgical pain management procedures is receiving increasing attention and concern. As a neurosurgeon, in fact, we mainly face those persistent neuropathic pains that are ineffective or ineffective after conventional treatment, although the proportion of pain patients in the population is small, the absolute number of cases is not small, and each of them is a treatment problem.
Neurosurgical analgesic procedures are effective treatments, especially for central pain, and are probably the most efficacious methods available, necessitating more widespread clinical application and research. With the continuous emergence and application of neuromodulation techniques such as nerve electrical stimulation, transcranial repetitive magnetic stimulation, and program-controlled drug infusion, it provides a new treatment concept, advanced technical means, diverse possibilities and broad application prospects for neurosurgical treatment of pain.