Deep Brain Stimulation Improves the Symptoms and Sensory Signs of Persistent Central Neuropathic Pain from Spinal Cord Injury: A Case Report

Abstract

Central neuropathic pain (CNP) is a significant problem after spinal cord injury (SCI). Pharmacological and non-pharmacological approaches may reduce the severity, but relief is rarely substantial. While deep brain stimulation (DBS) has been used to treat various chronic pain types, the technique has rarely been used to attenuate CNP after SCI. Here we present the case of a 54-year-old female with incomplete paraplegia who had severe CNP in the lower limbs and buttock areas since her injury 30 years prior. She was treated with bilateral DBS of the midbrain periaqueductal gray (PAG). The effects of this stimulation on CNP characteristics, severity and pain-related sensory function were evaluated using the International SCI Pain Basic Data Set (ISCIPBDS), Neuropathic Pain Symptom Inventory (NPSI), Multidimensional Pain Inventory and Quantitative Sensory Testing before and periodically after initiation of DBS. After starting DBS treatment, weekly CNP severity ratings rapidly decreased from severe to minimal, paralleled by a substantial reduction in size of the painful area, reduced pain impact and reversal of pain-related neurological abnormalities, i.e., dynamic-mechanical and cold allodynia. She discontinued pain medication on study week 24. The improvement has been consistent. The present study expands on previous findings by providing in-depth assessments of symptoms and signs associated with CNP. The results of this study suggest that activation of endogenous pain inhibitory systems linked to the PAG can eliminate CNP in some people with SCI. More research is needed to better-select appropriate candidates for this type of therapy. We discuss the implications of these findings for understanding the brainstem's control of chronic pain and for future progress in using analgesic DBS in the central gray.

Keywords: chronic pain; evoked pain; low-frequency stimulation; neuromodulation; pain severity; periaqueductal gray.

Figure 1

(A) Timeline of study. The subject underwent a comprehensive pain assessment (entire battery of pain tests) on week 2, prior to the two surgical procedures performed on weeks 6 and 7. This was followed by biweekly brief pain assessments (average pain intensity ratings past 7 days by patient in clinic) and periodic repeat comprehensive assessments postoperatively (weeks 20, 32 and 52). (B) Average pain intensity ratings past 7 days through duration of the study. Immediately following activation of the device the subject noticed a profound reduction of her central neuropathic pain (CNP).

Figure 2

The area of neuropathic pain was greatly reduced in the subject with activation of the device. Whereas before surgery (A) her pain was located at the anterior and posterior aspects of both legs and the superior buttocks, by the 20th week after surgery (B) pain was only perceived below the ankles. By the 32nd postoperative week (C) the pain extended back up to her mid-calf region of both legs and remained unchanged the remainder of the study (D).

Figure 3

Reduction of Neuropathic Pain Symptom Inventory (NPSI) and QST test scores with device activation. (A) The top graph shows paroxysmal, evoked and paresthesia/dysesthesia scores, all of which were reduced to minimal levels with stimulation. The bottom graph shows the reduction in the NPSI sum score. (B) Effects on QST measures. Whereas the subject had significant allodynia before surgery in response to cold and warm, these stimuli within the default minimum/maximum temperatures (0°C and 50°C, respectively) did not evoke pain sensations in follow-up.

Figure 4

Illustration showing the central role of the periaqueductal gray (PAG) in the modulation of various descending pain systems. Various neurotransmitter systems have been implicated in the treatment of central pain. The PAG has strong ascending and descending connections with each of these systems and is thus in a strong position to modulate CNP. Conventions for the arrows are shown at the bottom left of the figure. ACC, anterior cingulate cortex; Amyg, amygdala; PFC, prefrontal cortex; LC, locus coeruleus; NRM, nucleus raphe magnus; NTS, nucleus tractus solitarius.