Neuromodulation for Facial Pain

K.V. Slavin

• Publisher: S. Karger
• Year: 2020
• ISBN:
  9783318067958
• Topic: Medicine
• Subtopic: Neurosurgery

Neuropathic pain involving the face can be very severe and disabling; often, it is hard to control with conventional means and requires use of unconventional interventions on various parts of the trigeminal nociceptive pathways. For the last 60 years, neuromodulation has been used specifically for the treatment of intractable pain in different parts of the human body, including the face and head region. Despite such a long history and existence of many neuromodulation targets, there has not been a dedicated book that would summarize the entire spectrum of neuromodulation approaches that have been – and still are – used for treatment of facial pain. This book begins with dedicated chapters on classification of facial pain and anatomy of facial pain pathways and then dives into specific applications of neuromodulation starting from the periphery all the way to cerebral centers of pain processing, covering both invasive and non-invasive approaches. Written by experts from all over the word, the book offers an up-to-date comprehensive summary of neuromodulation techniques and modalities, providing the readers with a practical guide on clinical details of patient selection, modulation parameters, procedural details, and expected outcomes that may be used in daily clinical practice dealing with most difficult facial pain conditions.

Published online: September 9, 2020

Slavin KV (ed): Neuromodulation for Facial Pain. Prog Neurol Surg. Basel, Karger, 2020, vol 35, pp 141–161 (DOI: 10.1159/000509734)

______________________

Deep Brain Stimulation for Facial Pain

William G.B. SingletonReiko AshidaNikunj K. Patel

Department of Functional and Stereotactic Neurosurgery, North Bristol Trust, Bristol, UK

______________________

Abstract

Electro-modulation of subcortical deep brain structures by surgically implanted electrodes is now standard evidence-based treatment for movement disorders such as Parkinson’s disease and essential tremor and is approved for dystonia and obsessive-compulsive disorder under a humanitarian exemption. Historically, deep brain stimulation (DBS) for multiple indications has demonstrated acceptable complication rates, rare mortality, and reducing morbidity as the technology and the techniques of its application have advanced. DBS for the amelioration of pain has been performed since the early 1950s, and became widely used in the 1970s, when targeting the somatosensory thalamus was shown to be efficacious for intractable pain syndromes including facial pain. The technique fell out of favour in the late 1990s after 2 multicentre trials failed to meet end-point criteria. Since these trials, DBS for pain has remained for investigational or “off-label” use. Criticisms from previous literature have involved unsuitability of patient selection, as well as inconsistencies in neurosurgical technique. Clinical success with DBS for facial pain has been for the treatment of a variety of chronic neuropathic and nociceptive pain syndromes; including trigeminal neuropathy, post-herpetic neuralgia, deafferentation facial pain, “atypical” facial pain, cluster headaches and other trigeminal autonomic cephalalgias, as well as head and neck pathologies, most often which have been resistant to all other 1st- and 2nd-line medical and surgical treatments, when DBS has become a “last treatment option.” An enhanced understanding of the mechanisms of action of DBS for pain will enhance outcome, and appropriately prescribe evolving novel nuclear brain targets.

© 2020 S. Karger AG, Basel

Scientific Rationale

Craniofacial pain occurs in 10–25% of population with a higher prevalence in females compared to males [1]. It presents with a broad range of symptoms [2], is often severe and excruciating, and it is not uncommon for the severe distress to cause psychiatric illnesses such as depression and anxiety [3].

Common facial pain conditions include trigeminal neuralgia, trigeminal neuropathic pain, anaesthesia dolorosa and cluster headaches. Trigeminal neuralgia is characterised by severe lancinating pain affecting one or more branches of the trigeminal nerve, which occur in response to sensory trigger; and encouragingly medically refractory cases generally respond well to procedures directed at the Gasserian ganglion or trigeminal nerve root.

Trigeminal neuropathic pain presents as a constant burning, cramping, pricking and can be accompanied by a lancinating pain. It is differentiated from trigeminal neuralgia pain by the presence of constant burning pain [4]. Causes of trigeminal neuropathic pain include surgery, trauma and infections (such as post-herpetic pain). Anaesthesia dolorosa is a deafferentation pain, characterised by a chronic severe lancinating pain with an associated numbness over the face due to damage to the trigeminal nerve, by trauma or surgery. Injury to the first order trigeminal nerve results in spontaneous firing of second-order trigeminal pathway, resulting in constant pain without nociceptive stimulus [5]. With the underlying neuropathy, trigeminal neuropathic pain and anaesthesia dolorosa are more likely to be refractory to both medical and surgical interventions directed at the trigeminal nerve or its peripheral network, when advanced neurosurgical interventions directed at the central nervous targets need to be considered.

Cluster headache is a trigemino-autonomic syndrome, characterised by a severe unilateral pain around the orbital, supraorbital and temporal regions, with each attack typically lasting between 15 and 180 min. The pain is so severe that it is regularly described as worst-imaginable; and by female patients to be worse than childbirth pain [6]. About 10% of cases experience no significant remission, and about 15% of these do not respond to medication, and as a result surgery is considered. More invasive treatments include lesioning treatments, occipital nerve stimulation, sphenopalatine ganglion stimulation as well as deep brain stimulation (DBS) [7].

Several mechanisms that underpin the aetiology of facial pains have been suggested. Facial sensory innervation is primarily by the trigeminal nerve which divides into three divisions from the Gasserian ganglion, which are the ophthalmic (V1), maxillary (V2) and mandibular (V3) nerves. The peripheral branches of these divisions including the supratrochlear, infraorbital and mental nerves have been considered as neurostimulation targets [8]. The trigeminal nerve root enters the pons, with fibres travelling caudally in the spinal trigeminal tract before synapsing in the spinal trigeminal nucleus. The nociceptive afferents synapse with second-order neurons in the nucleus caudalis, which forms the inferior extent of the spinal trigeminal nucleus, and projects down to the level of C2. The sensory supply to the posterior aspect of the head is by the greater (C2), the lesser (C2,3) and the third occipital nerves, originating from the occipital plexus of the spinal nerves [9]. Connection between the spinal and trigeminal systems have been demonstrated by Goadsby and Hoskin [10]. The confluence of trigeminal and cervical afferents, often called the trigemino-cervical complex, at the level of C2 and C3 is the reason high cervical spinal cord and occipital nerves are targeted for treatment of headaches and facial pain [11].

Second-order neurons from the trigeminal nucleus caudalis cross the midline and ascend to synapse primarily in the ventral posteromedial (VPM) nucleus of the thalamus. From here, third-order neurons travel up to various regions in the cerebral cortex including the somatosensory cortex (primary and secondary), posterior parietal cortex, insula and anterior cingulate gyrus, and participate in the lateral pain transmission system. Whilst some cases of facial pain may respond to neuromodulation and stimulation applied to peripheral nerves or the high cervical spinal cord, DBS provides an opportunity to alleviate resistant facial pain by targeting the central processing of pain stimuli.

Pain comprises several components; therefore, its transmission pathways are complex [12]. Central nervous system pain transmission consists of two systems: the lateral and medial systems. The medial pain system consists of tracts connecting the medial nuclei of the thalamus (centromedian and parafascicular nuclei), through the brain stem ventral medulla and periaqueductal grey (PAG), and to the anterior cingulate gyrus and limbic system. This pathway is slower and is thought to modulate the affective component of pain. Advanced neurosurgical interventions directed at craniofacial pain pathways have attempted to target most of these anatomic locations initially with ablative procedures, and subsequently with DBS. Stimulation of any of these structures therefore may prove effective in altering pain perception or the central processing of nociceptive stimuli and is the rationale by which DBS is thought to be effective in selective patients with intractable chronic pain syndromes.

History of DBS for Facial Pain

The use of DBS for chronic pain in general (including in patients with facial pain) dates to the 1950s, a decade before Wall and Melzack came up with a conceptual theory for mechanisms of chronic pain control by means of electrical stimulation of the spinal cord and peripheral nerves [13]. For over 60 years, DBS has demonstrated significant analgesic benefits. James Olds and Peter Milner found that stimulation of septal regions in rodents elicited self-stimulation overwriting normal survival behaviours [14]. In attempts to treat patients with schizophrenia, stimulation of septal structures yielded serendipitous pain relief [15]. Sufferers of malignant oncological diseases and rheumatoid arthritis provided a willing and ethically justifiable cohort and, indeed, septal region DBS proved moderately effective in early studies. However, due to variable and non-sustained responses, finding alternative deep brain targets became a priority.

In subsequent years, a wide range of intracranial targets were investigated including the internal capsule (IC) [16], the ventral posterolateral (VPL) and VPM sensory nuclei of the thalamus, the centromedian parafascicular (CMPf) intralaminar region of the thalamus [17], the periventricular grey (PVG) and PAG [18, 19], the nucleus accumbens (NAc) [20] and anterior cingulate cortex (ACC) [21]. The choice of the targeted area depends on the type of pain and its distribution, and ultimately the experience of the treating multidisciplinary team. The PVG and PAG, and the sensory thalamus are the most commonly targeted in the published literature.

Medtronic reported results of chronic pain DBS from a trial using their first-generation model 3380 DBS electrode in 1976. The trial was affected by poor enrolment and high attrition rates, and subsequent analysis of the trial design revealed deficiencies in patient selection criteria resulting in a heterogeneous patient population, as well as inconsistencies in deep brain targets, the number of electrodes used as well as stimulation parameters. Significant and appropriate criticism of this trial led to a second Medtronic study using a more advanced electrode in 1990 (model 3387), following the 1989 US FDA jurisdiction requiring device manufacturers to undertake clinical trials documenting safety and efficacy before devices were granted official labelling. This trial was stopped after recruitment of 50 patients due to poor enrolment rates, high rates of patient withdrawal and limited evidence of efficacy. Neither trial was able to satisfy the trial endpoint of greater than 50% of patients achieving more than 50% pain relief. Medtronic therefore chose not to seek US FDA approval of their DBS system for analgesia and DBS for pain was subsequently designated investigational and “off-label” [22].

The VPM thalamic nucleus was demonstrated to be a suitable candidate for targeting head pain, from the results of original ablative procedures [23]. As a result, Hosobuchi et al. [24] successfully stimulated the VPM in 5 patients with facial pain, with reported good results. Despite these early successes, heterogeneous studies pursuing multiple chronic pain syndromes have resulted in variable reported efficacies and have kept DBS for pain purely as an investigational or...