Deep Brain Stimulation and Motor Cortex Stimulation for Chronic Pain
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.302471
Source of Support: None, Conflict of Interest: None
Keywords: Chronic pain, Motor cortex, neuromodulation, neurostimulation, peri-aqueductal gray, periventricular gray, thalamus
Pain is a complex territory. Chronic pain is even complex. It ceases to be a sensory phenomenon and becomes a global sensory mosaic. Spinoza calls pain as a ‘localized form of sorrow’. Perception of chronic pain involves multiple brain circuits. DBS has been successfully used in movement disorders for a while now. Initial use of DBS for the treatment of somatogenic pain principally targeted the central gray matter, or periaqueductal gray and periventricular gray (PAG/PVG) matter, and the sensory thalamus (ST). The initial work was done by Heath and Mickle in 1960s and is cited as the first effort to use electrical stimulation for treatment of chronic pain. The PAG/PVG matter was predominantly stimulated to treat nociceptive pain, while neuropathic pain was primarily treated with stimulation of the ST alone or in combination with PAG/PVG matter stimulation. Other targets evolved slowly as the knowledge of neural circuitry became more evident. Motor Cortex stimulation (MCS) is the result of serendipitous finding by Tsubokawa that subthreshold stimulation of precentral gyrus alleviates pain.,
Recent improvement in imaging, advanced methods and targeting and overall improved safety of electrode placement has led to exploration of more targets for central neurostimulation for chronic pain.
Pain pathways and theories of pain perception
Targets for deep brain stimulation for pain
The common targets used for DBS for pain are sensory thalamus (ST), medial thalamic nuclei such as centro-lateral (CL) and centro-medial parafscicular (CM-Pf), PAG/PVG area, Nucleus accumbence (NAcc), posterior hypothalamus (PH), septal nuclei, motor cortex and some other newly explored areas.
Sensory thalamus, variously named as nucleus ventralis caudalis (VC) or ventral posterolateral (VPL) and ventral posteromedial (VPM), is an important relay station in the pain pathway. Initial efforts by Mazars and Turnbull yielded good pain control by stimulating the sensory thalamus (ST). Though the mechanisms by which analgesia is produced following stimulation of the sensory thalamus are not completely understood, studies point to role of thalamic interlaminar nuclei, activation of cingulate by thalamic projections. Despite the incoherence of views about the underlying mechanisms, ST stimulation is commonly used as a target for chronic pain.
Patient selection: Neuropathic pain syndromes are more suitable for ST stimulation. Thalamic pain syndrome due to thalamic injury are not ideal candidates due to thalamic re-organization secondary to injury. Neuropathic pain secondary to brachial plexus root avulsions, arachnoiditis, post-laminectomy syndrome, neuropathy can be treated with thalamic stimulation.
Technical details: VC DBS is done awake like other DBS. The target is generally 10-11 mm from wall of the third ventricle, at the level of posterior commissure (PC) and at the anterior commissure- posterior commissure (AC-PC) line. In axial pain it can be done bilaterally. In addition to thalamic leads, CL leads can be placed [Figure 1]. Mapping of sensory thalamus is done with patient awake and appropriate pain coverage is obtained. After DBS lead implantation, the electrodes are connected to an extension which is externalized. The externalized part is connected to a handheld external stimulator. The trial lasts 5 days and the patient is kept in house, if possible in epilepsy monitoring unit (EMU). If sustained, more than 50% benefit is obtained, then the brain electrode is connected to an IPG. If the trial fails to give an adequate benefit, then the lead is removed. Programming is limited to small pulse-widths, rates around 50 to 100 Hz and use of contact 0 or 1. The amplitudes needed are extremely low. A word of caution is, when checking system impedance, make sure the lowest amplitude is used and patient is cautioned before for a surge in stimulation.
Centro-lateral (CL) and Centro-medial parafascularis (CM-Pf) complex
The midline and intralaminar nuclei (ILN) of thalamus as a whole play a role in awareness, affect, cognition and limbic pathways with each of the groups subserving a role in a different aspect of awareness. The following groups can be discerned:
The central pain matrix is subdivided into a medial and a lateral pain system. The lateral pain system (S1, S2) is primarily thought to have a role in discriminating the location and intensity of painful stimuli mediated through VPM and VPL, whereas the cognitive–evaluative- affective component of pain is mediated via medial pain system through CL. CL thalamotomy identifies a zone located in the posterior part of the CL that reduces the increased low frequency thalamocortical recurrent network activity via low-frequency desamplification and thalamic disinhibition, providing long term therapeutic efficiency coupled with sparing of the specific thalamocortical loops. By placing bilateral CL DBS the low-frequency thalamocortical power increases by reducing theta over-amplification and over-synchronization without reducing the specific and unaffected non-specific thalamocortical loops subserving remaining somatosensory and other hemispheric functions.
CM-Pf complex is also part of the medial pain system. Firing of CM-Pf cells is modified by painful stimuli. Thalamotomies targeting at the CM-Pf complex have yielded beneficial results for chronic pain.
Patient selection: Thalamic interlaminar nuclei modulation causes alteration to pain awareness and affect. So, it is much more effective as a global pain perception modulation tool. It may not affect focal pain but will affect general attitude of the patient towards the pain. So, it is better suited for larger areas of pain and in addition to ST DBS.
Technical details: CL DBS is target is 6.5 mm lateral to the wall of third ventricle, 2 mm behind the PC and at the AC-PC level [Figure 2]. For targeting using Morel Atlas More Details is especially useful. The entry should be medial and posterior to the thalamic lead if both the leads are being implanted. The mapping consists of low bursting pattern and micros-stimulation reveals awareness changes, anxiety or tingling [Figure 3]. While programming, the most useful contact is contact 0 or 1. Low pulse-width, rates below 50 Hz are best tolerated.
DBS treatment for pain of nociceptive origin predominately entails stimulation of the central gray matter, both the PAG matter and the PVG matter, the central gray matter, residing within the tegmentum of the midbrain, surrounds the cerebral aqueduct. Neuronal pathways traversing the central gray matter have demonstrated roles in reproduction, defensive behavior, and analgesia. DBS of the central gray matter has proved to elicit analgesic responses. It is most helpful in nociceptive pain. Stimulation of PVG/PAG matter inhibits nociceptive responses by increasing endogenous opioid levels. This effect was reversible with the administration of opioids antagonists in some cases. The endogenous opioid levels are also elevated in the third ventricle following electric stimulation of the PAG/PVG matter. Elevated levels of endogenous opioids following PAG/PVG matter stimulation may be critical in producing analgesic effects. However, it is still open to debate whether opioid release is a direct result of PAG/PVG matter stimulation or is a secondary effect.
Patient selection: Mostly nociceptive pain responds well to PAG/PVG stimulation. So, patients with intractable back pain, post-injury pain, musculoskeletal pain are good candidates. Some forms of neuropathic pain also respond to this when in combination with the nociceptive pain.
Technical details: PAG/PVG as a target is located close to the aqueduct. It is located 2-3 mm from wall of third ventricle 1-2 mm in front PC and tip goes down to the upper margin of superior colliculus. It is important to plan a trajectory away from the paraventricular vessels. The stimulation parameters are low amplitude, low rate and small pulse-width. If the patient has a pre-existing opioid infusion pump, it is important to dial the dose down before starting the stimulation.
Nucleus accumbence (NAcc), Ventral capsule-Ventral striatum (VC-VS)
The ventral portion of the caudate nucleus and nucleus accumbence together forms the ventral striatum and are considered to be the reward centers of the brain., DBS of this area is effective in improving the affective component of pain. Effective benefits due to spinal cord stimulation are also regarded to be a function of NAcc deactivation [Figure 4]. It does not alleviate pain but reduces the affective part, thus improving the quality of life. Choice of this target is based largely on the neuromatrix theory, where cognitive, affective, and sensory-discriminative spheres contribute equally to the overall pain experience.
Patient selection: Patients with a large affective burden associated with pain, could be candidates for this target. Controlling or reducing affective aspect of pain may allow us to reduce pain conditioning and pain-related disability.
Technical details: Target for VC-VS DBS is 6–7 mm lateral to midline, 1–2 mm anterior to the posterior border of the anterior commissure, 3–4 mm inferior to the AC-PC line. The trajectory is planned as much parallel to the anterior limb of internal capsule as possible. Burr holes are placed more anterior and lateral than usual [Figure 5]. Programming is done using high amplitudes with wide bipolar settings and higher pulse-width. Rate varies between 50 to 100 Hz.
DBS of the posterior hypothalamic region was introduced to treat pain arising from acute cluster headache (CH) attacks. Hypothesized mechanisms of action are activation or inhibition of neuronal pathways traversing the posterior hypothalamus. These neuronal pathways include ascending catecholaminergic and descending pathways from the hypothalamus to the brain stem and spinal cord. The posterior hypothalamus also contains cells concentrated with melatonin and opiate peptides. Traversing autonomic neuronal pathways through the targeted area led to theories that the induction of analgesia following electric stimulation includes a hormonal mechanism. However, this hypothesis was disproved through close patient assessment following chronic DBS stimulation. Schoenen et al. utilized DBS for hypothalamic stimulation of a small number of patients suffering from chronic CH. One week following DBS, two patients showed small decreases in urinary secretion of melatonin but no other hormonal abnormalities. Schoenen et al. concluded that the induced hypoalgesia was independent of a reduction in sensitivity or perception of pain. They also concluded that the mechanism was more complex than any simple pathway leading to hypoalgesia.
Patient selection: Patients with intractable cluster headaches, neuropathic face pain, short-lasting trigeminal autonomic cephalalgia (SUNCT) are candidates for this.
Technical details: This is a functionally extraordinarily complex target. The target is located 3 mm behind the midcommissural point, 5 mm below the midcommissural point, and 2 mm lateral to the midline. The stimulation parameters have a small pulse-width (60 microseconds), rate or 180 Hz and amplitudes around 1 to 3 volts.
Motor Cortex stimulation
Motor Cortex stimulation (MCS) has been used for a variety of chronic medically refractory pain syndromes such as facial neuropathic pain, atypical face pain, post-stroke central pain, thalamic pain, brachial plexus avulsion pain, phantom limb pain, post-herpetic neuralgia, Wallenberg syndrome pain, complex regional pain syndrome, Multiple sclerosis pain, spinal cord injury or pain secondary to post-traumatic brain injury.,,, Majority of these studies are retrospective case series or small prospective randomized trials, and there is a paucity of literature on the efficacy of MCS for chronic neuropathic face pain in large multicenter randomized controlled trials., Monsalve evaluated the efficacy of MCS for facial chronic neuropathic pain in a systematic review and reported that of 126 relevant studies (MCS for chronic pain) and 118 patients, 100 (84.7%) patients underwent permanent implantation and 84% of these had good pain relief. Another review reported response rates of 72.6% and 45.3% with invasive and noninvasive brain stimulation for chronic pain respectively. In our experience of 26 patients with trigeminal neuropathic and post-stroke pain who underwent epidural motor cortex stimulation, 50% of them achieved > 50% alleviation in the intensity of pain. Overall MCS efficacy was good or satisfactory in 60% of patients with chronic painful conditions. Another prospective double-blinded crossover trial comparing the efficacy of MCS between ON and OFF states in patients with chronic neuropathic condition reported that MCS in ON state has significant benefits in terms of both pain relief and improvement in quality of life with no loss of efficacy over time. Velasco et al. in a double-blind study reported 100% pain relief in two patients with thalamic pain (V2/V3 distribution) and post-herpetic neuralgia (V1 distributions) with MCS. Mechanism of action of MCS is still debated but it largely based on modulation of thalamic hyperactivity and thalamocortical dysrhythmias.
Patient selection: Any neuropathic or deafferentation pain responds well to MCS. One of the common indications is anesthesia dolorosa or post-treatment deafferentation face pain. Post-stroke pain also responds well to MCS.
Technical details: Functional Magnetic resonance guided; navigation aided small craniotomy is performed [Figure 6]a. Functional techniques are used to Motor evoked potential and a grid is used to localize the central sulcus and pre and post central gyrus [Figure 6]b. N20-P20 phase reversal is also used to confirm the location of central sulcus [Figure 6]c. Somatotopic organization of precentral gyrus is then identified using epidural stimulation. Two epidural paddle electrodes are then stitched to dura across the pre and postcentral gyrus [Figure 6]d. In hospital trial is done for 5-7 days. Programming parameters of 40 Hz frequency (25-55 Hz), 60-180 milliseconds pulse width, 1.5-4 volts amplitude (according to the seizure threshold) and bipolar stimulation with cathodes over the motor cortex and anodes over the sensory cortex. Chronic stimulation is usually done in a cycling mode with 3 hours ON/3 hours OFF state and should not produce paresthesia. Pain relief is generally achieved several minutes following the onset of stimulation. The common complications associated with MCS include seizures, wound infections, hemorrhage, brain edema and neurological deficits.
DBS can be a last resort for a variety of neuropathic and chronic pain syndromes which are refractory to medical therapy or other neuromodulation techniques. DBS has gained significant popularity with improving efficacy, safety, and applications beyond movement disorders. There is an immense interest in the role of DBS for chronic pain conditions which are refractory to other conventional therapies. DBS can be used for refractory pain syndromes such as neuropathic pain, deafferentation pain, brachial plexus avulsion pain, chronic low back pain, failed back surgery syndrome, and cluster headaches.,,,
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Conflicts of interest
There are no conflicts of interest.
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