Implantable technology for pain management

Neuropathic pain is a well-recognized chronic pain condition. This can have a significant impact in patients' quality of life. Neuromodulation is defined by the International Neuromodulation Society as ‘the therapeutic alteration of activity in the central or peripheral nervous system either electrically or pharmacologically’. Electrical stimulation can be performed at the motor cortex, deep brain, spinal cord, dorsal root ganglion, peripheral nerve and peripheral nerve field. Pharmacological modulation is achieved by directly infusing drugs to the central nervous system. Although neuromodulation has become increasing popular, it is still currently believed to be underused in treating neuropathic pain. This modality has provided us with a non-pharmacological approach to manage patients with neuropathic pain. Patients should have been assessed by a multidisciplinary team before undergoing neuromodulation. This review highlights the present and future management of patients with chronic intractable pain using neuromodulation.     

Implantable technology for pain management

Chronic pain has now been recognized as a disease entity in its own right. Significant numbers of patients suffer from intractable chronic pain. Neuromodulation has been defined by the International Neuromodulation Society as ‘the therapeutic alteration of activity in the central or peripheral nervous system either electrically or pharmacologically’. It can be achieved either by electrical stimulation of peripheral nerves, spinal cord or brain, or by delivering pharmacological agents directly into the intrathecal, epidural or intracerebroventricular sites. Neuromodulation is expensive, invasive and not without complications. Patients requiring neuromodulation should undergo multidisciplinary assessment for suitability. Clinical effectiveness is possible with appropriate patient selection and attention to technical details.     

Traitement neurochirurgical de la douleur chronique

Neurosurgical treatment of pain used two kind of techniques: 1) Lesional techniques interrupt the transmission of nociceptive neural input by lesionning the nociceptive pathways (drezotomy, cordotomy, tractotomy…). They are indicated to treat morphine-resistant cancer pain and few cases of selected neuropathic pain. 2) Neuromodulation techniques try to decrease pain by reinforcing inhibitory and/or to limit activatory mechanisms. Chronic electrical stimulation of the nervous system (peripheral nerve stimulation, spinal cord stimulation, motor cortex stimulation…) is used to treat chronic neuropathic pain. Intrathecal infusion of analgesics (morphine, ziconotide…), using implantable pumps, allows to increase their efficacy and to reduce their side effects. These techniques can improve, sometimes dramatically, selected patients with severe and chronic pain, refractory to all other treatments. The quality of the analgesic outcome depends on the relevance of the indications.     

Implantable devices for pain control: spinal cord stimulation and intrathecal therapies

Untreated chronic pain is costly to society and to the individual suffering from it. The treatment of chronic pain, a multidimensional disease, should rely on the expertise of varying health care providers and should focus not only on the neurobiological mechanisms of the process but also on the psychosocial aspects of the disease. Implantable devices are costly and invasive, and such efficacious therapies should be used only when more conservative and less costly therapies have failed to provide relief of pain and suffering. Spinal cord stimulation provides neuromodulation of neuropathic, but not nociceptive, pain signals and when used for appropriate indications in the right individuals provides approximately 60–80% long-term pain relief in 60–80% of patients trialled for efficacy. Intrathecal therapies with opioids such as morphine, fentanyl, sufentanil or meperidine – or non-opioids such as clonidine or bupivacaine – provide analgesia in patients with nociceptive or neuropathic pain syndromes. Baclofen, intrathecally, provides profound relief of muscle spasticity due to multiple sclerosis, spinal cord injuries, brain injuries or cerebral palsy.     

Ausgew?hlte interventionelle Verfahren zur Behandlung chronischer Schmerzen

Approximately 5?C8 million people in Germany suffer from chronic pain. Some patients can obtain relief from specific interventional techniques. In detail these are blocks of the sympathetic chain and peripheral nerve blocks, regional anesthetic techniques close to the spinal cord and neuromodulation. Part 1 of this article presents peripheral nerve blocks using the example of intercostal blocks and blocks of the sympathetic chain. Peripheral nerve blocks are important for postoperative pain treatment. Only a few methods are used for chronic pain and this applies primarily to the intercostal block which is used for the treatment of pain occurring after thoracotomy, intercostal neuralgia and pain associated with infiltration of cancer. Blocks of the vegetative nervous system are accomplished on the ganglions of the head and the sympathetic chain and are therefore most commonly applied to treat headache, neuropathic and sympathetic pain in the area of abdomen and the extremities.     

Neurosurgical approaches to pain treatment

In a multidisciplinary approach to the management of chronic pain, neurosurgical methods are an indispensable part of the therapeutic armamentarium. With the exception of percutaneous interventions for trigeminal neuralgia and facet joint syndromes, most ablative pain surgery procedures (neurotomy, rhizotomy, sympathectomy, etc.) have been replaced by neuromodulatory approaches such as electrical stimulation of the central nervous system (CNS). However, cordotomy is still a valuable operation for certain forms of cancer related pains (Pancoast's syndrome, breakthrough pain) which are relatively resistant to pharmacotherapy. Another example of ablative surgery is the dorsal root entry zone (DREZ) operation, which is generally the only treatment option for pain due to root avulsion and segmental pain in spinal cord injury. Spinal cord stimulation (SCS) has proven to be most useful for the management of pain following peripheral nerve injury (including complex regional pain syndromes) and rhizopathy. For these conditions which are otherwise often therapy resistant, SCS may produce substantial and long-lasting pain relief in 60-70% of the patients. Considering that such pains are common and the fact that SCS has been shown to be cost-effective, this treatment is no doubt at present underused. Complications and side-effects are very rare. SCS has also been found to be useful for pain in peripheral vascular disorders and angina pectoris. In the latter condition the overall results are favorable in about 80% of patients with a significant reduction of the frequency and severity of angina attacks and the need for nitrates. Stimulation of the motor cortex is a novel and promising treatment of central, post-stroke pain and painful trigeminal neuropathy.     

Selected interventional methods for the treatment of chronic pain: Part 1: peripheral nerve block and sympathetic block

Approximately 5-8 million people in Germany suffer from chronic pain. Some patients can obtain relief from specific interventional techniques. In detail these are blocks of the sympathetic chain and peripheral nerve blocks, regional anesthetic techniques close to the spinal cord and neuromodulation. Part 1 of this article presents peripheral nerve blocks using the example of intercostal blocks and blocks of the sympathetic chain. Peripheral nerve blocks are important for postoperative pain treatment. Only a few methods are used for chronic pain and this applies primarily to the intercostal block which is used for the treatment of pain occurring after thoracotomy, intercostal neuralgia and pain associated with infiltration of cancer. Blocks of the vegetative nervous system are accomplished on the ganglions of the head and the sympathetic chain and are therefore most commonly applied to treat headache, neuropathic and sympathetic pain in the area of abdomen and the extremities.     

The Proximal Tap or “Central Tinel” Sign in Central Dysesthetic Syndrome After Spinal Cord Injury

ABSTRACT

Diffuse, chronic, and dysesthetic pain following spinal cord injury (SCI) has been described by several authors under different terms. As illustrated by the two patients described here, central dysesthetic syndrome (CDS) can be mistaken for musculoskeletal, peripheral neuropathic or visceral disease in SCI patients. In these patients, an added clue to the central neuropathic nature of their symptoms was allesthesia and allodynia to light touch or tapping over areas rostral to the level of injury; this may be called the proximal tap or “central Tinel” sign.     

Novel trends in pain management – Neuromodulation

Neuromodulation is one of the most exciting developments in pain management. Spinal cord stimulation, peripheral nerve stimulation and intrathecal drug delivery systems are used increasingly to provide pain relief and improve the quality of lives of patients in whom conventional medical management has failed to provide satisfactory results. Though initial costs may be high, these techniques have proven to be cost effective in the long term. A good understanding of the principles and techniques involved in neuromodulation and their benefits and limitations is essential to achieve best results.     

Surgical management of chronic pain

Chronic pain is believed to affect around 14 million people in England. It impacts on society and places a high demand on healthcare with an estimated cost to the UK National Health Service £10 billion per annum. Management of chronic pain is therefore a major clinical challenge. Many patients will be managed effectively in community or primary care while a proportion will require specialist secondary and tertiary care pain services. For these a multidisciplinary approach with pharmacological and non-pharmacological strategies will improve quality of life but there will still be a proportion with significant symptoms that cannot be helped in this fashion. Selected patients with intractable pain may benefit from targeted surgical procedures, reducing the long-term physical, emotional and financial burden that results from their situation. The technical and clinical challenge is determining ‘who’, ‘what’, ‘where’ and ‘when’ in order to provide the best possible long-term outcome and quality of life. Over the past three decades, with the exception of procedures for trigeminal neuralgia, the bias in neurosurgical intervention for chronic pain relief has changed from ablative lesioning towards reversible, low-risk neuromodulation techniques wherein electrical stimulation of part of the nervous system or intrathecal medication is used to control pain or modify physiology.     

Neuroimaging of neuropathic pain: review of current status and future directions

The goal of this review is to discuss the various imaging modalities to study neuropathic pain and its future implication in understanding pain network, for the diagnosis and management of patients with chronic neuropathic pain. Neuropathic pain is characterized by pain secondary to lesions or dysfunction of the central nervous system (CNS) or the peripheral nervous system. Neuropathic pain is generally chronic and disabling, and responds poorly to conventional treatment. Although our understanding of the imaging changes in chronic pain state is evolving, we still face practical challenges in implementing these finding to objectively diagnose and follow treatment response in patients with chronic pain and to guide targeted and individualized treatment to each chronic pain condition.     

Pathology and possible mechanisms of nervous system response to disc degeneration

Degeneration of the intervertebral disc is clinically considered to be an important source of pain in patients with low-back pain. Disc deterioration and/or degeneration may influence the nervous system by stimulation of nociceptors in the anulus fibrosus, causing nociceptive pain that is often referred to as discogenic pain. The stimulation of the nociceptors may be of mechanical or inflammatory origin. Deterioration of a disc with loss of normal structure and weight-bearing properties may lead to abnormal motions that cause mechanical stimulation. This theory is supported by the fact that patients commonly experience an increase in pain with weight-bearing and certain movements. In addition, an ingrowth of vessels and nerve fibers into deeper layers of the anulus fibrosus has been observed in degenerated discs. A large number of inflammatory and signaling substances, such as tumor necrosis factor and interleukins (interleukin-1beta, interleukin-6, and interleukin-8), may also play a role in the development of back pain. Independent of stimulus of the nociceptors, the pain impulses are conducted through myelinated A delta fibers and unmyelinated C fibers to the dorsal root ganglion and continue by way of the spinothalamic tract to the thalamus and the somatosensory cortex. In response to stimulation of the nociceptors in the disc, the somatosensory system may increase its sensitivity, resulting in a nonfunctional response; that is, normally innocuous stimuli may generate an amplified response (peripheral sensitization). When disc degeneration leads to a disc herniation, the adjacent nervous system structures, such as the nerve roots or the dorsal root ganglion, can be affected, causing neuropathic pain of mechanical or biochemical origin. Disc deterioration also influences other spinal structures, such as facet joints, ligaments, and muscles, which can also become pain generators. Thus, disc degeneration may be responsible for the development of chronic low-back pain without being the actual pain focus. Both nociceptive and neuropathic pain can be modulated at higher centers, both at the spinal and the supraspinal levels (central sensitization). The altered magnitude of perceived pain is often referred to as neural plasticity and is considered to play a critical role in the evolution of chronic pain. Together with the complexity of the nervous system and pain modulation mechanisms, psychological aspects may also play a role in the response of the nervous system in patients with chronic low-back pain caused by disc degeneration.     

Neuromodulation in epilepsy

Neuromodulation strategies have been proposed to treat a variety of neurological disorders, including medication-resistant epilepsy. Electrical stimulation of both central and peripheral nervous systems has emerged as a possible alternative for patients who are not deemed to be good candidates for resective procedures. In addition to well-established treatments such as vagus nerve stimulation, epilepsy centers around the world are investigating the safety and efficacy of neurostimulation at different brain targets, including the hippocampus, thalamus, and subthalamic nucleus. Also promising are the preliminary results of responsive neuromodulation studies, which involve the delivery of stimulation to the brain in response to detected epileptiform or preepileptiform activity. In addition to electrical stimulation, novel therapeutic methods that may open new horizons in the management of epilepsy include transcranial magnetic stimulation, focal drug delivery, cellular transplantation, and gene therapy. We review the current strategies and future applications of neuromodulation in epilepsy.     

Proteomics in Neuropathic Pain Research

Neuropathic pain is often caused by nerve injury or dysfunction in the peripheral and central nervous system and is frequently associated with allodynia and hyperalgesia. The underlying molecular mechanisms of neuropathic pain are largely unknown, and therefore, pharmacologic treatment is insufficient in many cases. To elucidate translational and posttranslational modifications in the nervous system that arise after nerve injury, a number of proteomic studies have been performed using different animal neuropathy models. The results of these proteomic approaches are summarized in this review to provide a better overview of proteins that are involved into the pathogenesis of nerve injury and neuropathic pain. This might allow a better understanding of the pathophysiologic signaling pathways in this impairment, facilitate the discovery of specific biomarkers, and thus promote the development of novel pain therapies.     

肿瘤坏死因子-α和神经病理性疼痛

背景 神经病理性疼痛(Neuropatlic pain,NP)是神经系统损伤引起的一种慢性疼痛,其发病机制复杂,至今尚缺乏有效的治疗药物.目的 肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)是神经损伤和神经炎症过程早期释放的重要致炎细胞因子.近年来,许多研究显示外周及脊髓免疫细胞激活后表...     

Efficacy and Safety of Sacral and Percutaneous Tibial Neuromodulation in Non-neurogenic Lower Urinary Tract Dysfunction and Chronic Pelvic Pain: A Systematic Review of the Literature

ContextNeuromodulation is considered in patients with non-neurogenic lower urinary tract dysfunction (LUTD) not responsive to conservative treatment.ObjectiveTo systematically review the available studies on efficacy and safety of sacral neuromodulation (SNM) and percutaneous tibial nerve stimulation (PTNS) in non-neurogenic LUTDs not responsive to conservative treatments.Evidence acquisitionA literature research was conducted in PubMed/Medline and Scopus, restricted to articles in English, published between January 1998 and June 2017, with at least 20 patients and 6 mo of follow-up.Evidence synthesisTwenty-one reports were identified. Concerning SNM, the improvement of ≥50% in leakage episodes ranged widely between 29% and 76%. Overall dry rate ranged between 43% and 56%. Overall success/improvement rate in PTNS varied between 54% and 59%. Symptom improvement or efficacy in interstitial cystitis/bladder pain syndrome patients appeared to be lower compared with other indications in both techniques. Safety data showed fewer side effects in patients submitted to PTNS.ConclusionsNeuromodulation gives good results and is a safe therapy for patients with overactive bladder or chronic nonobstructive urinary retention with long-lasting efficacy. Moreover, PTNS has been shown to have good success rates and fewer side effects compared with SNM. These data have to be confirmed with long-term follow-up.Patient summarySacral neuromodulation can improve low urinary tract symptoms in selected patients; it appears to be a safe therapy for nonresponders to standard medical therapies. Percutaneous tibial nerve stimulation (PTNS) is a less invasive technique that gives good results in short time with fewer side effects. However, we must consider that PTNS has not been tested in the long term and results are lower if compared with SNM.     

Augmentative treatment of chronic deafferentation pain syndromes after peripheral nerve lesions.

Deafferentation pain syndromes developing after peripheral nerve lesions are difficult to treat. According to the follow-up (mean: 39.5 months) of 6 patients suffering from causalgic pain we will present our method of augmentative therapy in chronic neuropathic pain caused by peripheral nerve lesions, i.e., peripheral nerve stimulation (PNS), spinal cord stimulation (SCS) and chronic intrathecal opioid infusion. None of the patients showed intraoperative or follow-up complications. Evaluated by visual analogue scales all patients reported a good to excellent pain relief (75-100%). (1) Regarding the favourable long-term results of PNS, this method should be considered in cases of mononeuropathic pain syndromes. (2) Neuropathic pain syndromes which are not assignable to a singular nerve lesion, can often be managed effectively by SCS. (3) In contrast to the widespread opinion, deafferentation pain syndromes of central or peripheral origin can be treated satisfactorily by intrathecal opiate administration.     

Ausgew?hlte interventionelle Verfahren zur Behandlung chronischer Schmerzen

Approximately 5-8 million people in Germany suffer from chronic pain and some patients can profit from specific interventional techniques. In detail these are regional anesthetic techniques close to the spinal cord, neuromodulation, blocks of the sympathetic chain and peripheral nerve blocks. Part 2 of the article presents regional anesthetic techniques close to the spinal cord and neuromodulative methods. Regional anesthetic techniques close to the spinal cord are of high importance for the treatment of chronic low back pain although the efficiency is highly disputed due to the lack of evidence. Neuromodulation includes amongst others intrathecal pharmacotherapy and spinal cord stimulation, which are used for highly selected patients and can lead to very good results for these patients.     

Field/peripheral stimulation: Surgical indications and technique

Peripheral stimulation, similar to spinal cord stimulation, is a form of neuromodulation that aims to treat chronic pain by directly targeting peripheral nerves, and thus altering peripheral pain pathways leading to pain relief. Implantation is performed within two stages. The first stage, or trial phase, is performed under local anesthesia and attempts to identify the appropriate peripheral nerve causing pain. The second stage, performed under general anesthesia, involves placement of an internal battery/generator for the implanted electrode. Indications for peripheral stimulation includes the following: migraine, occipital neuralgia, cluster headache, neuropathic facial pain, complex regional pain syndrome, and chronic lower back pain.