Facial Pain Update: Advances in Neurostimulation for the Treatment of Facial Pain

Craniofacial pain, including trigeminal neuralgia, trigeminal neuropathic pain, and persistent idiopathic facial pain, is difficult to treat and can have severe implications for suffering in patients afflicted with these conditions. In recent years, clinicians have moved beyond treating solely with pharmacological therapies, which are generally not very effective, and focused on new interventional pain procedures. These procedures have evolved as technology has advanced, and thus far, early results have demonstrated efficacy in small patient cohorts with a variety of craniofacial pain states. Some of the most promising interventional pain procedures include peripheral nerve field stimulation, high-frequency spinal cord stimulation, sphenopalatine ganglion stimulation, and deep brain stimulation. This review focuses on a better understanding of craniofacial pain and emerging interventional pain therapies. With the advent of newer miniature wireless devices and less invasive implantation techniques, this should allow for more widespread use of neurostimulation as a therapeutic modality for treating craniofacial pain. Larger studies should assist in best practice strategies vis-à-vis traditional pharmacological therapies and emerging interventional pain techniques.     

Interventional management of neuropathic pain: NeuPSIG recommendations

Neuropathic pain (NP) is often refractory to pharmacologic and noninterventional treatment. On behalf of the International Association for the Study of Pain Neuropathic Pain Special Interest Group, the authors evaluated systematic reviews, clinical trials, and existing guidelines for the interventional management of NP. Evidence is summarized and presented for neural blockade, spinal cord stimulation (SCS), intrathecal medication, and neurosurgical interventions in patients with the following peripheral and central NP conditions: herpes zoster and postherpetic neuralgia (PHN); painful diabetic and other peripheral neuropathies; spinal cord injury NP; central poststroke pain; radiculopathy and failed back surgery syndrome (FBSS); complex regional pain syndrome (CRPS); and trigeminal neuralgia and neuropathy. Due to the paucity of high-quality clinical trials, no strong recommendations can be made. Four weak recommendations based on the amount and consistency of evidence, including degree of efficacy and safety, are: 1) epidural injections for herpes zoster; 2) steroid injections for radiculopathy; 3) SCS for FBSS; and 4) SCS for CRPS type 1. Based on the available data, we recommend not to use sympathetic blocks for PHN nor radiofrequency lesions for radiculopathy. No other conclusive recommendations can be made due to the poor quality of available data. Whenever possible, these interventions should either be part of randomized clinical trials or documented in pain registries. Priorities for future research include randomized clinical trials, long-term studies, and head-to-head comparisons among different interventional and noninterventional treatments.     

Spinal Cord Stimulation to Treat Postthoracotomy Neuralgia: Non–Small-Cell Lung Cancer: A Case Report

Surgery is the mainstay of therapy for resectable-type tumors associated with non–small-cell lung cancer. Today, thoracotomy and video-assisted thoracotomy are surgical options. The prevalence of chronic pain with neuropathic symptoms is relatively high after thoracotomy. Spinal cord stimulation to treat such pain has received limited attention in the literature. The aim of this article is to report on the use of spinal cord stimulation in a single case of neuralgia after thoracotomy with lobectomy to treat non–small-cell lung cancer. At 24 months after implantation of the spinal cord stimulation system, the patient reported >75% pain relief, an overall improvement in quality of life—described as less pain with breathing, and improved functional ability pertaining to arm movements—and improved sleep patterns. This detailed case presentation provides a qualitatively weighted investigation into spinal cord stimulation for postthoracotomy neuralgia against the backdrop of oncologic care. Further investigations relying on quantitative assessment tools are necessary to further explore this form of therapy in this patient population. In the single case reported here, the use of spinal cord stimulation suppressed intractable pain targeted at the T6 and T7 dermatomes of the chest wall in the manifestation of postthoracotomy neuralgia.     

Neurotoxins in the Neurobiology of Pain

Migraine is a common, chronic, incapacitating, neurovascular disorder that affects an estimated 12% of the population. Understanding the basic mechanisms of pain is important when treating patients with chronic pain disorders.
Pain, an unpleasant sensory and emotional experience, is usually triggered by stimulation of peripheral nerves and often associated with actual or potential tissue damage. Peripheral nerve fibers transmit pain signals from the periphery toward the spinal cord or brain stem. The different diameter pain fibers (A and C) vary in the speed of conduction and the type of pain transmitted (eg, sharp versus dull). When stimulated, peripheral pain fibers carrying sensory input from the body enter at different layers of the dorsal horn, which is then propagated toward the thalamus via the spinothalamic tract within the spinal cord. Conversely, sensory input from the face does not enter the spinal cord but enters the brain stem via the trigeminal nerve.
This review describes in detail the neurobiological mechanisms and pathways for pain sensation, with a focus on migraine pain.     

Spinale Neurostimulation

After the initial clinical reports of Shealy 1967 dorsal column stimulation (DCS) was first introduced in Germany by Krainick (Freiburg) and Winkelmüller (Hannover) in 1972. At first, the success rate in unselected patients was unsatisfactory. The results improved with careful patient selection and better technical equipment allowing preliminary testing procedures before definitive implantation. The authors' own results in 335 patients treated by intermittent spinal cord stimulation (SCS) with implanted devices between 1972 and 1989 show that long-term beneficial effects can be obtained in pain of neurogenic origin rather than in nociceptor pain. Guidelines for the use of SCS were proposed by the German Society of Neurosurgery in 1990. The best indications and target group are cases with radicular low-back pain after failed back surgery, stump and phantom pain, pain states following partial lesions of brachial/lumbar plexus and peripheral nerves, sympathetic dystrophy and rest pain in peripheral vascular disease (PVD). Possible indications for SCS are pain after incomplete lesions of spinal cord or cauda equina, postherpetic neuralgia, sclerodermia and PVD. Failures must be expected in pain states related to progressive malignant disease and complete deafferentation after spinal lesions or root avulsion.     

Multiple Sclerosis-Related Central Pain Disorders

Central neuropathic pain is common in multiple sclerosis (MS), and its prevalence increases with physical disability. Sufficient evidence links dysesthetic pain, trigeminal neuralgia, Lhermitte’s sign, and painful tonics spasms to plaque formation in the spinal cord and brain, whereas the association with headache and back pain remains unclear. Management varies according to the pain in question. For dysesthetic pain, drugs in use for neuropathic pain in general are recommended as first-line treatment, and emerging evidence suggests some benefit from cannabinoids and levetiracetam. Because of unique characteristics of MS-related trigeminal neuralgia, ganglion and root level neuroablative procedures are worth considering before microvascular decompression. Overall, the lack of controlled clinical trials, together with our limited understanding of the pathophysiological mechanisms involved, form a hindrance to a systematic and rational management of MS-related pain.     

Neuralgia

Neuralgia is defined here as chronic pain, without a known anatomic substrate; in the distribution of spinal or cranial nerves. Among the cranial neuralgias are tic douloureux, other trigeminal neuralgias, and occipital neuralgia. The spinal neuralgias include postherpetic neuralgia, postthoracotomy neuralgia, tabes dorsalis, and posttraumatic neuralgia.     

Glossopharyngeal neuralgia referred from a pontine lesion

Paroxysmal pain in the form of glossopharyngeal neuralgia is less frequent and less well understood than that of trigeminal neuralgia. Diagnostic confusion can arise especially when both conditions occur in the one patient. We report a patient with a 20-year history of left-sided glossopharyngeal neuralgia with trigger zones in both the trigeminal and glossopharyngeal dermatomal distributions. Magnetic resonance imaging revealed a single T2-weighted hyperintense signal in the left pons with no other abnormality. It is postulated that ephaptic transmission between central pain fibers and the trigeminal or glossopharyngeal fibers, which both enter the spinal trigeminal tract, resulted, respectively, in conventional and "referred" glossopharyngeal neuralgia.     

Cost benefit analysis of neurostimulation for chronic pain

OBJECTIVES: To assess the healthcare utilization of patients with intractable chronic neuropathic pain treated with spinal cord stimulation and peripheral nerve stimulation and to provide a cost-benefit analysis. METHODS: The case records of 222 consecutive patients who received spinal cord stimulation or peripheral nerve stimulation implants at the Cleveland Clinic Foundation between 1990 and 1998 were reviewed retrospectively. Patients were asked to complete a Neurostimulation Outcome Questionnaire designed to gather data on utilization of healthcare resources starting 1 year before surgical implantation. These data were pooled and net differences in events per patient per year, before and after device implantation were calculated and modeled to 2000 cost data obtained from the Medicare Fee Schedule and Healthcare Financing Administration. RESULTS: Neurostimulation Outcome Questionnaires were returned by 128 patients. The mean patient age was 46 +/- 12.5 years (range 21-71 years) and the mean implant duration was 3.1 +/- 2.3 years (range 0.5-8.9 years). The mean per patient total reimbursement of spinal cord stimulation/peripheral nerve stimulation absent pharmacotherapy was $38,187. Patients treated with spinal cord stimulation/peripheral nerve stimulation for pain management achieved reductions in physician office visits, nerve blocks, radiologic imaging, emergency department visits, hospitalizations, and surgical procedures, which translated into a net annual savings of approximately $30,221 and a savings of $93,685 over the 3.1-year implant duration. The large reduction in healthcare utilization following spinal cord stimulation/peripheral nerve stimulation implantation resulted in a net per patient per year cost savings of approximately $17,903. DISCUSSION: The reduced demand for healthcare resources by patients receiving neurostimulation suggests that peripheral nerve stimulation and spinal cord stimulation treatment, although associated with relatively high initial costs, demonstrates substantial long-term economic benefits. Thus, neurostimulation should be considered as a viable option for the early treatment of patients with intractable chronic neuropathic pain.     

Dynamic mechanical allodynia in neuropathic pain

Thirty-four patients with various forms of neuropathic pain have been examined with respect to two parameters of dynamic mechanical allodynia: the effect of repetitive stimulation on pain intensity; and refractory period. Pain intensity increased with repetitive stimulation ('windup') in most patients with neuropathic pain of peripheral origin, while it was not observed in patients with central neuropathic pain. While a non-responsive period occurs after tactile allodynic elicitation in patients with trigeminal neuralgia (Kugelberg and Lindblom, 1959), it was not seen in any case of neuropathic pain, including trigeminal neuropathy. The findings have implications for diagnosis, and require pathophysiological elucidation in terms of revealed differences.     

Spinal baclofen in trigeminal neuralgia. A case report

Oral baclofen, the most often prescribed antispastic drug, has been shown to be effective in trigeminal neuralgia. Spinal application of baclofen leads to a complete supression of spasticity even in cases in which no previous oral antispastic medication achieved a response. Since these results suggest that spinal administration of baclofen is superior to oral baclofen, spinal injections of this drug (100 mug) were tested in a patient with severe trigeminal neuralgia that was unresponsive to oral medication. This was followed by complete suppression of the neuralgic symptoms, which however reoccurred if baclofen administration was stopped. Spinal baclofen has also been effective during long-term infusion with an implanted pump for more than 1 year. Spinal baclofen infusion seems to be a possibility in the treatment of severe trigeminal neuralgia resistant to other forms of therapy.     

Cervicomedullary junction spinal cord stimulation for head and facial pain

Objective.— To review our experience with cervicomedullary junction spinal cord stimulation (SCS), to alleviate head and facial pain. Background.— There is a dearth of literature regarding the use of spinal cord stimulation for treating head and facial pain. Design.— We performed a Boolean search of the electronic medical record (1990‐2009) and identified 35 patients (9 men, 26 women) for whom the senior author (J.J.M) trialed paddle lead cervicomedullary junction stimulation (CMJ‐S) for intractable head or facial pain. Twenty‐five patients (71.4%) had a successful trial with subsequent implantation of SCS hardware and 10 patients (28.6%) experienced a failed trial. Pain syndromes were categorized into diagnostic groups: trigeminal deafferentation pain (TDP), trigeminal neuropathic pain (TNP), occipital pain/neuralgia, post‐herpetic neuralgia (PHN), and post‐stroke facial pain. Follow‐up via structured telephone interview was obtained in 25 patients (71.4%). Results.— Among the 25 patients available for follow‐up, 16 patients (64%) underwent implantation and 9 patients (36%) had a failed trial of CMJ‐S. The mean patient age and length of follow‐up was 47.3 years old (20‐78 years old) and 53.4 months (2‐120 months), respectively. On a 0‐10 pain intensity scale (0 being no pain and 10 being the worst degree of pain), a mean pretrial pain level of 9.6 (range 7‐10) had been reduced to a mean of 4.8 (0‐10) at follow‐up. Successful trial and subsequent implantation occurred in 7 patients with TDP (70%), 4 patients with TNP (80%), both patients with PHN (100%), and in the single patient with post‐stroke facial pain (100%) but in only 2 patients (28.6%) with occipital neuralgia/pain. At the time of telephone interview, 4 of the implanted patents (25%) had their hardware removed because of loss of effectiveness (3) and infection (1). The other 12 implanted patients (75%) continue to use CMJ‐S on a daily basis and insist that it has improved their quality of life. Six current users (50%) of CMJ‐S have been able to decrease their use of oral pain medications. Complications in the implanted group included infection (1), uncomfortable paresthesias from breakdown of connecting wire insulation (1), and gradual loss of effectiveness (3). Conclusions.— Our preliminary experience suggests that patients suffering from TDP, TNP, and PHN may respond favorably to CMJ‐S whereas patients with occipital neuralgia/pain are rarely palliated by this neuromodulatory approach.     

Functional magnetic resonance imaging within the rat spinal cord following peripheral nerve injury

Functional magnetic resonance imaging (fMRI) was used to detect the effects of graded peripheral nerve injury at the spinal level. Graded peripheral nerve injury in rats was accomplished by transection of nerves entering the spinal cord at the L3 and L4 levels of the spinal cord segments. Electrical stimulation of the hindpaw was used to elicit activity within the spinal cord. The stimulation experimental paradigm consisted of 62 functional images, 5 slices each, with a total of 3 rest and 2 stimulation periods. A 9.4 T MRI system and a quadrature volume rf coil covering the lumbar spinal cord were used for the fMRI study. Sets of fast spin echo images were acquired repeatedly following sham preparatory surgery under control conditions and in rats following sham surgery (pre nerve cut), followed by L3 nerve and then L4 nerve section. In rats with sham surgery, there was a significant activation within the dorsal horn of slices corresponding to L3 and L4 spinal cord segments. Following section of the L3 nerve, there was a reduction in the number of active voxels in the L3 and L4 spinal cord segments. The activation was reduced further by sectioning of the L4 nerve. Thus, following an increasing loss of axonal connections to the spinal cord, there was a decreasing number of active voxels within the spinal cord. The results demonstrate that spinal fMRI in the rat has sufficient sensitivity to detect within the spinal cord the effects of a graded reduction in peripheral connectivity.     

Identification of cytokines and signaling proteins differentially regulated by sumatriptan/naproxen

Objectives.— The goal of this study was to use protein array analysis to investigate temporal regulation of stimulated cytokine expression in trigeminal ganglia and the spinal trigeminal nucleus in response to co‐treatment of sumatriptan and naproxen sodium or individual drug. Background.— Activation of neurons and glia in trigeminal ganglia and the spinal trigeminal nucleus leads to increased levels of cytokines that promote peripheral and central sensitization, which are key events in migraine pathology. While recent clinical studies have provided evidence that a combination of sumatriptan and naproxen sodium is more efficacious in treating migraine than either drug alone, it is not well understood why the combination therapy is superior to monotherapy. Methods.— Male Sprague–Dawley rats were left untreated (control), injected with capsaicin, or pretreated with sumatriptan/naproxen, sumatriptan, or naproxen for 1 hour prior to capsaicin. Trigeminal ganglia and the spinal trigeminal nucleus were isolated 2 and 24 hours after capsaicin or drug treatment, and levels of 90 proteins were determined using a RayBio® Label‐Based Rat Antibody Array (RayBiotech, Norcross, GA, USA). Results.— Capsaicin stimulated a >3‐fold increase in expression of the majority of cytokines in trigeminal ganglia at 2 hours that was sustained at 24 hours. Significantly, treatment with sumatriptan/naproxen almost completely abolished the stimulatory effects of capsaicin at 2 and 24 hours. Capsaicin stimulated >3‐fold expression of more proteins in the spinal trigeminal nucleus at 24 hours when compared to 2 hours. Similarly, sumatriptan/naproxen abolished capsaicin stimulation of proteins in the spinal trigeminal nucleus at 2 hours and greatly suppressed protein expression 24 hours post‐capsaicin injection. Interestingly, treatment with sumatriptan alone suppressed expression of different cytokines in trigeminal ganglia and the spinal trigeminal nucleus than repressed by naproxen sodium. Conclusion.— We found that the combination of sumatriptan/naproxen was effective in blocking capsaicin stimulation of pro‐inflammatory proteins implicated in the development of peripheral and central sensitization in response to capsaicin activation of trigeminal neurons. Based on our findings that sumatriptan and naproxen regulate expression of different proteins in trigeminal ganglia and the spinal trigeminal nucleus, we propose that these drugs function on therapeutically distinct cellular targets to suppress inflammation and pain associated with migraine.     

Differential effects of the 5HT1B/1D receptor agonist naratriptan on trigeminal versus spinal nociceptive responses

In vivo electrophysiological assays in anesthetized rats have been used to compare the effects of the 5HT_1B/1D receptor agonist, naratriptan, on central trigeminal nociceptive processing from dural and cutaneous inputs with its effects on nociceptive processing in the spinal cord. Naratriptan inhibited responses of single trigeminal neurons, to noxious electrical and mechanical stimulation of the dura and face, dose dependently by a maximum of 67±3% and 70±18%, respectively, at 3 mg kg⁻¹ i.v. In contrast, naratriptan did not affect spinal dorsal horn neuronal responses to noxious mechanical stimulation of the hind-paw. These findings suggest that 5HT_1B/1D receptors have differential effects on nociceptive processing in the trigeminal versus spinal dorsal horns and provide a potential explanation for the lack of general analgesic effects of brain penetrant 5HT_1B/1D agonist antimigraine drugs.     

Modification of blood flow to the extremities by electrical stimulation of the nervous system.

Sixteen patients who had electrical stimulation applied to various portions of the nervous system were examined for increase in blood flow to the extremities. Clinical observations and a one-channel plethysmograph were used to measure arterial dilatation. Seven patients had transcutaneous stimulation applied over the cervical or thoracic spinal cord, peripheral nerves, or low lumbar region; eight had electrical stimulators implanted over the spinal cord in attempts to relieve intractable pain or some of the symptoms of multiple sclerosis; and one patient had electrical stimulators implanted over the C-6 dorsal roots for small artery disease of the upper extremities. Twelve of 13 patients who had electrical stimulation applied to the spinal cord or dorsal roots had significant arterial dilatation in one or more extremities. Electrical stimulation applied to the ulnar nerves did cause arterial dilatation. One patient did not show any change in the central arterial pressure curve during transcutaneous stimulation of the cervical spinal cord.     

三叉神经周围支撕脱术治疗三叉神经痛疗效观察

目的探讨三叉神经周围支撕脱术治疗三叉神经痛的近期疗效。方法对23例确诊为原发性三叉神经痛者,施行神经撕脱术。第一支1例,第二支11例,第三支11例。结果本组23例,22例有效,1例无效。8例在术后10d有一过性跳疼。术后半年至8年复发的6例中,第二支2例,第三支4例,其中3例又再次手术。结论三叉神经痛周围支撕脱术治疗三叉神经痛近期疗效好,远期疗效还待进一步观察。     

Orofazialer Schmerz - Trigeminusneuralgie und posttraumatische Trigeminusneuropathie

Neuropathic pain is the result of a lesion or disease of the somatosensory system in the peripheral or central nervous system. Classical trigeminal neuralgia and posttraumatic trigeminal neuropathy are pain disorders which oral and maxillofacial surgeons and dentists are confronted with in the differential diagnostics in routine daily practice. The etiopathogenesis of classical trigeminal neuralgia is attributable to pathological blood vessel-nerve contact in the trigeminal nerve root entry zone to the brain stem. The typical pain symptoms are characterized by sudden stabbing pain attacks. The pharmaceutical prophylaxis is based on the individually titrated administration of anticonvulsant drugs. The indications for interventional treatment are dependent on the course, response to drug treatment, resilience and wishes of the patient. The neuropathic mechanism of posttraumatic trigeminal neuropathy originates from nerve damage, which leads to peripheral and central sensitization with lowering of the pain threshold and multiple somatosensory disorders. The prophylaxis consists of avoidance of excessive acute and long-lasting pain stimuli. Against the background of the biopsychosocial pain model, the treatment of posttraumatic trigeminal neuropathy necessitates a multimodal, interdisciplinary concept.     

Occipital Neuromodulation: Ultrasound Guidance for Peripheral Nerve Stimulator Implantation

We report a case of chronic left‐sided occipital neuralgia in a 21‐year old female patient. The patient in question suffered from chronic greater occipital neuralgia for a duration of many years, which had been refractory to other conservative medical management strategies. Blockade of the greater occipital nerve with local anesthetic was consistently useful in attenuating the patient's pain, though the effects were always short lived. Consequently, a successful trial of greater occipital nerve stimulation was undertaken. Compared with spinal cord stimulation, peripheral nerve stimulation devices are often more difficult to precisely place given limited ability to visualize soft tissues with traditional fluoroscopic guidance. Additionally, there are anatomic subtleties relevant to the greater occipital nerve that potentially complicate stimulator lead placement, both from the standpoint of optimal neuromodulation efficacy and maximum safety. Ultrasound technology is a maturing imaging modality that allows soft tissue visualization and is consequently useful in addressing each of these aforementioned concerns. The specific use of high‐frequency ultrasound guidance for this procedure simplified the initial device placement and allowed proper visualization of soft tissue structures, which facilitates precise device deployment. Additionally, the ability to identify relevant vascular structures may further increase the safety of stimulator lead placement. The potential advantages of ultrasound‐augmented procedural techniques, specifically as they pertain to occipital stimulator lead placement, are discussed with particular emphasis on potentially decreasing intraoperative and postoperative complications while optimizing stimulation efficacy.     

Release of glutamate, nitric oxide and prostaglandin E2 and metabolic activity in the spinal cord of rats following peripheral nociceptive stimulation

Peripheral tissue injury and inflammation may result in a facilitated spinal nociceptive transmission and central sensitization. Particularly, nitric oxide (NO) and prostaglandins (PGs) have been shown to be key mediators involved in the induction and maintenance of this state. By means of spinal cord microdialysis we have determined interstitial glutamate, NO (NO2-/NO3-), PGE2, glycerol, glucose and lactate concentrations in the dorsal horns of the spinal cord following peripheral nociceptive stimulation to gain further insight into the link between excitatory neurotransmitters and metabolic functions in the spinal cord during nociception. Formalin and zymosan injection into one hind paw evoked a biphasic release of glutamate and NO with the glutamate peaks preceding those of NO. Moreover, zymosan induced a biphasic increase of interstitial glycerol concentrations accompanied by an increase of interstitial lactate indicating metabolic disturbances. In contrast, formalin injection led to an elevation of dialysate glucose concentrations which may be interpreted as an indication of enhanced metabolic activity. The sequential release of glutamate and NO in the dorsal horns of the spinal cord in response to peripheral nociceptive stimulation supports the theory that NO may act as a retrograde transmitter. The metabolic changes observed after formalin and zymosan injection suggest that an intense peripheral nociceptive stimulation may not only activate but also disturb metabolic activity and possibly membrane integrity in the spinal cord.