Introduction 

When the nervous system stays in a highly activated state, central neuronal sensitisation is caused. This results in increased activity of nerve cells and signal transmission, causing the nervous system to be sensitive to pain. This heightened sensitivity is due to ion channel modulation, less inhibition, and improper changes in nerve pathways.¹  

Central pain is a long-term type of nerve-related pain that occurs due to damage to the central nervous system, which includes the brain and spinal cord. Blood vessel abnormalities in the brain and the spinal cord, or injury to the brain or spinal cord, are the common causes that lead to central pain.²

 Central neuropathic pain (CNP), a complex disease, has been estimated to affect 10% of the population. Even with many treatment options, people still suffer from it.³

Overview of neuromodulation

Neuromodulation therapies manage chronic pain with a range of treatment options, including electrical stimulation.⁴ In order to inhibit, excite, or modulate the activity of neuronal networks and to elicit a therapeutic effect, surgical neuromodulation encompasses all the methods that use implantable devices delivering electricity or chemicals to alter the nerve signal transmission.⁵

Neuromodulation methods include non-invasive central (transcranial magnetic stimulation [rTMS], transcranial direct current stimulation [tDCS]), peripheral (transcutaneous electrical nerve stimulation [TENS], neuromuscular electrical stimulation [NMES], and peripheral nerve stimulation [PNS]) techniques. There are also invasive central (deep brain stimulation [DBS], motor cortex stimulation [MCS], and spinal cord stimulation [SCS]) and peripheral (dorsal root ganglion stimulation [DRGS]) approaches.⁶

Deep brain stimulation (DBS) explained

Deep Brain Stimulation (DBS) involves implanting electrodes into specific deep brain regions for the purpose of modulating neural function to treat neurological/psychiatric conditions.⁷ Deep brain stimulation (DBS) is a neurosurgical intervention.⁸ Although many ideas have appeared on the scene, the exact mechanisms of action of DBS are still unknown.⁹ 

 The sensory thalamus (ST), the medial thalamic nuclei like the centro-lateral (CL) and centro-medial parafascicular (CM-Pf), PAG/PVG region, Nucleus accumbens (NAcc), posterior hypothalamus (PH), septal nuclei, motor cortex, and a few other recently studied areas are the most commonly employed targets for DBS for pain.¹⁰ The rostral anterior cingulate cortex (ACC) and the periventricular and periaqueductal grey matter (PVG/PAG) are the DBS sites that are targeted very often for the modulation of chronic neuropathic pain. The target of simulation depends on the source of pain.¹¹

Clinical outcomes

The meta-analysis indicates that DBS reliably lowers chronic pain. Out of the 966 chronic pain patients who underwent DBS (340 for DBS-P and 625 for DBS-O), the average age of the patients was 52.8 ± 11.2 years, and the average duration of pain was 11.6 ± 10.3 years. The results of the meta-analysis indicated that DBS lowered chronic pain considerably, with the DBS-P group having an average decrease in pain by 47.67 ± 20.01%.¹²

There is no data that deep-brain stimulation has any ability to decrease pain in the long term.¹³ For some etiologies, DBS for pain is effective in the long term. Nine amputees, seven brachial plexus injuries, thirty-one strokes, thirteen spinal pathologies, fifteen head and face pain, and ten miscellaneous cases were among the 107 patients referred over 12 years and of whom 85 received DBS. 66% of individuals who received implants experienced benefits, and outcomes improved in 89% of patients after amputation and 70% after stroke, with aetiology-dependent improvement.¹⁴

Differences in target and surgical procedures complicate the interpretation of most research. DBS of the PVG/PAG (79%)  or the PVG/PAG with sensory thalamus/internal capsule had the best long-term pain relief rate of 87%.¹⁵

Clinical considerations

Deep-brain stimulation or motor cortex stimulation may be an option for patients whose pain cannot be managed with pharmacological medications or less invasive methods.¹⁶ Pain should have an identifiable physical cause and not respond well to medications or cause side effects when treated. DBS is contraindicated in patients with irreversible coagulopathy and ventriculomegaly.⁸

Surgical issues, hardware complications, and stimulation-dependent complications are the three categories of clinically significant complications of DBS.  Venous infarcts and air embolisms, intracranial haemorrhages, and electrode misplacements are the surgical complications.  Infection, electrode dislocation, or fracture are hardware complications.  Stimulation Complications: Effective stimulation requires proper patient selection, accurate DBS lead implantation, and effective postoperative DBS programming. Failure to fulfil any one of these three conditions results in stimulation issues.¹⁷

Despite deep brain stimulation (DBS) having well-documented benefits, access may be limited by the high costs of the procedure, which are highly variable. Inflation and exchange rate changes gave a mean cost of USD 21,496.07 ± USD 8,944.16, USD 40,942.85 ± USD 17,987.43 for the DBS device, and USD 47,632.27 ± USD 23,067.08 for the full treatment regimen to one year of follow-up.¹⁸

The standard procedures of obtaining informed consent can adequately communicate to patients the nature and probability of the numerous known risks involved with new neurosurgical procedures like DBS.  However, as these procedures are novel, they also involve unknown risks, and thus a more cautious method of obtaining informed permission is required.¹⁹

Current research and future directions 

Classic target sites for deep-brain stimulation are the central medial, parafascicular thalamic nuclei, and septal area. The most frequently described locations are the periventricular grey matter (PVG) and PAG, and the ventral caudal or VPL/VPM sensory nucleus of the thalamus. Novel sites presently being researched include the mesial thalamic nuclei, VC region of the ventral anterior limb of the internal capsule, and ventral striatum (VS).16 The emotional components of the brain, such as anterior cingulum (ACC) and ventral striatum/anterior limb of the internal capsule (VS/ALIC), have been explored lately for treating pain, which was found to be effective in 20-70% of the patients.²⁰

 DBS requires surgical insertion of the electrodes, which makes it an invasive technique. Hence, its therapeutic application is limited. Acoustic, electronic, optical, and magnetic signals are the basis of second-generation brain stimulation techniques like focused ultrasound, temporal interference, near-infrared optogenetics, and nanomaterial-mediated magnetic stimulation. These techniques hold tremendous potential for neuromodulation. In order to establish the optimal strategy and confirm that these techniques are, indeed, next-generation noninvasive DBS technologies, interdisciplinary collaboration will be needed.²¹

Conclusion

Central neuropathic pain, which is provoked by disease or injury, is hard to treat due to its complex mechanism and limited response to therapeutics. In patient selective, neuromodulation modalities—specifically, Deep Brain Stimulation (DBS) have shown credible results in reducing chronic central pain. DBS has yielded variable but impressive pain alleviation in certain disorders like amputation and stroke-induced pain by disrupting certain areas of the brain to control pain messages. However, the success rate is highly dependent on the suitability of the patient, target, and optimal surgery and postsurgical techniques.

Clinical issues related to DBS are hardware failures, stimulation-related failures, and surgical issues, despite its benefits.  Also, limited accessibility and expensive treatment costs have deterred its acceptance.

In the subsequent years, studies are expanding the possibilities of DBS targets and non-invasive neuromodulation techniques like aimed ultrasound waves and nanotechnology-based stimulation.  These technologies have been developed to exceed the limited confines of conventional methods of DBS and further to achieve more convenient and safer conditions. Trials on patients and interdisciplinary studies are significant for enhancing patient outcomes, safety, and efficiency. Under identical circumstances, DBS is promising, but further advancement and more tailored modalities are still necessary for effective treatment of central pain.

FAQs

What is central pain?

The pain that affects the brain or spinal cord is called Central pain or central neuropathic pain (CNP). 

How does deep brain stimulation (DBS) reduce pain?

Implanted electrodes in DBS transmit electrical signals to targeted regions of the brain that are involved in pain processing and disrupt the abnormal pain signals.

Is DBS a curative treatment for chronic central pain?

DBS can not cure central pain. It may significantly reduce pain in selected patients with conditions like stroke or amputation-related pain. 

Who are the patients suitable for DBS?

Patients with severe and prolonged central pain who had not responded to medications or other treatments, and if the source of pain is identifiable. Also, patients must not be associated with conditions that make the surgery risky.

Is the mechanism of DBS understood?

The exact mechanism is not known, but it works by altering abnormal nerve impulse transmission in specific brain circuits.