Deep Brain Stimulation for Chronic Pain: Mechanisms, Clinical Applications, limitations and Future Directions

Lou'I Al-Husinat¹Majdala Al-Bataineh¹Rama Hayajneh²Dania O. Haneyah²Qabas Alrawabdeh³Rasha Bani Melhem⁴Aiman Al Sharei⁵Mohammed I. A. Ismail⁶Saif Azzam¹Sarah Al Sharie^7*Giustino Varrassi⁸

• ¹Faculty of Medicine, Yarmouk University, Irbid, Jordan
• ²Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
• ³Azraq refugee camp hospital, International medical corps, Amman, Jordan
• ⁴Jordan ministry of health hospitals, Amman, Jordan
• ⁵Department of Pharmacology, Community Medicine and Clinical Skills Faculty of Medicine, The Hashemite University, Azzarqa, Jordan
• ⁶Anesthesiology department, Mut’ah school of medicine, Al-Karak, Jordan
• ⁷Vanderbilt University Medical Center, Nashville, United States
• ⁸Fondazione Paolo Procacci, Rome, Italy

Chronic pain is a complex, multifactorial condition affecting millions worldwide, often resistant to conventional treatments. Deep brain stimulation (DBS), a reversible and adjustable neurosurgical intervention, has emerged as a promising therapeutic approach for the treatment-resistant chronic pain. This narrative review examines the evolving clinical role of DBS in pain management, highlighting its mechanisms, efficacy, limitations, and future directions. We discuss the neurophysiological underpinnings of chronic pain, emphasizing structural and functional changes in brain regions such as the medial prefrontal cortex, limbic system, and somatosensory pathways. DBS targets including the periaqueductal/periventricular grey (PAG/PVG), sensory thalamus, anterior cingulate cortex (ACC), and ventral striatum are explored in relation to pain modulation and affective processing. Evidence from clinical studies demonstrates significant variability in response rates, largely influenced by patient selection, lead placement, and pain etiology. While DBS shows greatest success in nociceptive and neuropathic pain syndromes such as cluster headaches, phantom limb pain, and failed back surgery syndrome, its efficacy in deafferentation pain remains limited. Recent innovations, including dual-target stimulation, advanced imaging for surgical planning, and combination therapies with spinal cord or vagal nerve stimulation, offer promising avenues for enhancing outcomes. Despite its off-label status for pain in many countries, accumulating data support DBS as a viable treatment in select cases of intractable pain. Continued research and standardized protocols are essential for optimizing patient selection, refining targeting strategies, and improving long-term outcomes.