The three largest studies within the past decade that focused specifically on DBS of the sensory thalamus include research by Yamamoto et al., Hamani et al., and Pereira et al. [23–25]. Yamamoto et al. reported on a case series in which 18 patients with phantom limb or stump pain received DBS of the thalamic nucleus ventralis caudalis. Fourteen of the 18 achieved long-term satisfactory pain control. The authors noted that bipolar stimulation of wide areas from the anterodorsal part to the center of the ventralis caudalis appeared to be more effective than focal stimulation of a more limited area. They also partly attributed their success to the use of exclusion criteria, which were based on pharmacological classification by the morphine, thiopental, and ketamine tests [23].

A case series by Hamani et al. included 21 patients with chronic neuropathic pain, which was characterized by burning, aching, dysesthesias, and/or allodynia. Of the 13 who had electrodes placed solely in the ventrocaudalis thalamic nucleus, five experienced an insertional effect, and ten had a successful stimulation trial, but only two of the ten experienced relief of pain that lasted for more than 1 year [24].

Most recently, Pereira et al. conducted a one-year prospective case series that included 12 patients with either phantom limb pain or brachial plexus avulsion who received DBS of the VPL sensory thalamus. At the end of the year, 11 of the 12 reported persistent pain relief. The authors noted that they focused on the VPL, instead of the PVG, because the latter is a target with: (1) more clearly delineated intraoperative stimulation effects, (2) less risk of side effects, and (3) a strong connection to appendicular pain syndromes [25].

The three largest studies within the past decade that have focused on DBS of the PVG/PAG include research by Rasche et al., Owen et al., and Boccard et al. [2, 7, 26]. Each of these investigators also cotargeted the VPL/VPM during the procedure, which is sometimes considered a second-line approach following unsuccessful PVG/PAG stimulation [2]. Rasche et al. published a case series that included 56 patients with failed back surgery syndrome, anesthesia dolorosa, phantom limb pain, spinal cord injury, poststroke pain, or postherpetic pain. Of these, 32 underwent permanent DBS implantation, with favorable results observed in 22. The best long-term results were seen in failed back surgery patients, the majority of whom preferred to have both PVG and VPL electrodes activated [7].

Owen et al. reported on a case series that included 47 patients, most of whom had pain related to stroke, phantom limb, or brachial plexus injury. Of these, 38 underwent permanent DBS implantation, with six lost to follow-up. Of the remaining 32 patients, PVG stimulation was optimal in 17 and associated with the highest degree of pain relief. A combination of PVG and thalamic stimulation was optimal in 11 patients, and thalamic stimulation alone was optimal in four patients.

Most recently, Boccard et al. published a prospective case series including 85 patients with phantom limb pain, stump pain, plexus injury, poststroke pain, spinal cord injury, or facial pain. Of these, 74 underwent permanent DBS implantation, but 15 were lost to follow-up. Of the remaining 59 implanted patients, 39 experienced favorable results, with 21 receiving only PVG stimulation, five receiving only VPL/VPM stimulation, and 13 receiving stimulation of both targets. The greatest success was observed in patients with phantom limb pain. For most cases of neuropathic pain, the authors recommend targeting the PVG first and proceeding to VPL DBS only if the patient does not experience an intraoperative sensation of pleasant warmth with PVG DBS [2].

The most recent research focusing specifically on DBS of the internal capsule includes two studies by Namba et al. and one study by Franzini et al. [27–29]. Namba published two case series focusing on patients with poststroke pain, thalamic pain syndrome, or multiple sclerosis. In the first series, seven patients underwent trial stimulation of the posterior limb of the internal capsule and, of these, six received permanent DBS systems. Three experienced good results, two experienced fair results, and one experienced poor results after follow-up ranging from 9 to 31 months [27]. Based on the results of the second case series, in which 8 of 11 patients experienced fair to excellent pain relief, Namba et al. determined that the most posteromedial part of the internal capsule (i.e., the nucleus reticularis pulvinaris or area triangularis) is the most effective target [28]. More recently, Franzini et al. published a case report of the successful use of internal capsule DBS for a patient with poststroke pain, based on 5 years of follow-up [29].

Several investigators have published research focusing on DBS of the center median–parafascicular complex [30–32]. For example, Andy et al. reported on a case series, in which five patients with intractable thalamic pain syndrome or headache received DBS of the CM–Pf complex and related intralaminar nuclear structures. All five patients experienced good to excellent pain improvement. The authors hypothesize that the CM–Pf complex and thalamic intralaminar system are both directly and indirectly involved in the mechanisms for both central and peripheral generated pain. Furthermore, they believe that DBS of these targets relieves pain by altering the excitability state and/or the thalamic discharge patterns [30].

Krauss et al. published an abstract comparing CM–Pf stimulation to sensory thalamus stimulation in a prospective case study involving 11 patients with chronic neuropathic pain. Ten of the patients underwent permanent DBS implantation and experienced significant pain improvement with CM–Pf stimulation, relative to both preoperative pain and VPL/VPM stimulation [31]. The same group also published a subsequent study of CM–Pf DBS for three patients with neuropathic pain and concomitant movement disorders. All three patients experienced improvement in their movement disorders, and two of the three experienced improvements in pain that were significant enough to prompt permanent implantation of the DBS system [32].

The posterior hypothalamus (PH) is typically targeted in an effort to treat refractory, chronic cluster headache (CCH ). General consensus is that approximately 50–60% of CCH patients have a positive response to DBS of the PH [9, 10]. For example, Fontaine et al. published a randomized, controlled, double-blinded trial, in which 11 patients received active or sham stimulation. At 1 month, there was no significant difference in headache frequency between the two groups; however, after 1 year of active stimulation, six experienced at least a 50% decrease in headache frequency, and three of the six were pain free [33].