Trigeminal neuralgia: New classification and diagnostic grading for practice and research

Trigeminal neuralgia (TN) is an exemplary condition of neuropathic facial pain. However, formally classifying TN as neuropathic pain based on the grading system of the International Association for the Study of Pain is complicated by the requirement of objective signs confirming an underlying lesion or disease of the somatosensory system. The latest version of the International Classification of Headache Disorders created similar difficulties by abandoning the term symptomatic TN for manifestations caused by major neurologic disease, such as tumors or multiple sclerosis. These diagnostic challenges hinder the triage of TN patients for therapy and clinical trials, and hamper the design of treatment guidelines. In response to these shortcomings, we have developed a classification of TN that aligns with the nosology of other neurologic disorders and neuropathic pain. We propose 3 diagnostic categories. Classical TN requires demonstration of morphologic changes in the trigeminal nerve root from vascular compression. Secondary TN is due to an identifiable underlying neurologic disease. TN of unknown etiology is labeled idiopathic. Diagnostic certainty is graded possible when pain paroxysms occur in the distribution of the trigeminal nerve branches. Triggered paroxysms permit the designation of clinically established TN and probable neuropathic pain. Imaging and neurophysiologic tests that establish the etiology of classical or secondary TN determine definite neuropathic pain

Neuropathic pain: redefinition and a grading system for clinical and research purposes.

Pain usually results from activation of nociceptive afferents by actually or potentially tissue-damaging stimuli. Pain may also arise by activity generated within the nervous system without adequate stimulation of its peripheral sensory endings. For this type of pain, the International Association for the Study of Pain introduced the term neuropathic pain, defined as "pain initiated or caused by a primary lesion or dysfunction in the nervous system." While this definition has been useful in distinguishing some characteristics of neuropathic and nociceptive types of pain, it lacks defined boundaries. Since the sensitivity of the nociceptive system is modulated by its adequate activation (e.g., by central sensitization), it has been difficult to distinguish neuropathic dysfunction from physiologic neuroplasticity. We present a more precise definition developed by a group of experts from the neurologic and pain community: pain arising as a direct consequence of a lesion or disease affecting the somatosensory system. This revised definition fits into the nosology of neurologic disorders. The reference to the somatosensory system was derived from a wide range of neuropathic pain conditions ranging from painful neuropathy to central poststroke pain. Because of the lack of a specific diagnostic tool for neuropathic pain, a grading system of definite, probable, and possible neuropathic pain is proposed. The grade possible can only be regarded as a working hypothesis, which does not exclude but does not diagnose neuropathic pain. The grades probable and definite require confirmatory evidence from a neurologic examination. This grading system is proposed for clinical and research purposes

Effects of Lockdown Restrictions and Impact of Anxiety and Depression Symptoms in People With Chronic Pain During the Covid-19 Pandemic: A 13-wave Longitudinal Study

In early 2020, countries across the world imposed lockdown restrictions to curb the spread of the Covid-19 coronavirus. Lockdown conditions, including social and physical distancing measures and recommended self-isolation for clinically vulnerable groups, were proposed to disproportionately affect those living with chronic pain, who already report reduced access to social support and increased isolation. Yet, empirical evidence from longitudinal studies tracking the effects of prolonged and fluctuating lockdown conditions, and potential psychological factors mediating the effects of such restrictions on outcomes in chronic pain populations, is lacking. Accordingly, in the present 13-wave longitudinal study, we surveyed pain intensity, pain interference, and tiredness in people with chronic pain over the course of 11 months of the Covid-19 pandemic (April 2020–March 2021). Of N = 431 participants at baseline, average completion rate was ∼50% of time points, and all available data points were included in linear mixed models. We examined the impact of varying levels of lockdown restrictions on these outcomes and investigated whether psychological distress levels mediated effects. We found that a full national lockdown was related to greater pain intensity, and these effects were partially mediated by depressive symptoms. No effects of lockdown level were found for pain interference and tiredness, which were instead predicted by higher levels of depression, anxiety, pain catastrophising, and reduced exercise. Our findings are relevant for improving patient care in current and future crises. Offering remote management options for low mood could be particularly beneficial for this vulnerable population in the event of future implementation of lockdown restrictions

Mechanistically informed non-invasive peripheral nerve stimulation for peripheral neuropathic pain: a randomised double-blind sham-controlled trial

Background Induction of long-term synaptic depression (LTD) is proposed as a treatment mechanism for chronic pain but remains untested in clinical populations. Two interlinked studies; (1) A patient-assessor blinded, randomised, sham-controlled clinical trial and (2) an open-label mechanistic study, sought to examine therapeutic LTD for persons with chronic peripheral nerve injury pain. Methods (1) Patients were randomised using a concealed, computer-generated schedule to either active or sham non-invasive low-frequency nerve stimulation (LFS), for 3 months (minimum 10 min/day). The primary outcome was average pain intensity (0-10 Likert scale) recorded over 1 week, at 3 months, compared between study groups. (2) On trial completion, consenting subjects entered a mechanistic study assessing somatosensory changes in response to LFS. Results(1) 76 patients were randomised (38 per group), with 65 (31 active, 34 sham) included in the intention to treat analysis. The primary outcome was not significant, pain scores were 0.3 units lower in active group (95% CI - 1.0, 0.3; p = 0.30) giving an effect size of 0.19 (Cohen's D). Two non-device related serious adverse events were reported. (2) In the mechanistic study (n = 19) primary outcomes of mechanical pain sensitivity (p = 0.006) and dynamic mechanical allodynia (p = 0.043) significantly improved indicating reduced mechanical hyperalgesia. Conclusions Results from the RCT failed to reach significance. Results from the mechanistic study provide new evidence for effective induction of LTD in a clinical population. Taken together results add to mechanistic understanding of LTD and help inform future study design and approaches to treatment. Trial registration ISRCTN53432663

Phantom limb pain, cortical reorganization and the therapeutic effect of mental imagery

Using functional MRI (fMRI) we investigated 13 upper limb amputees with phantom limb pain (PLP) during hand and lip movement, before and after intensive 6-week training in mental imagery. Prior to training, activation elicited during lip purse showed evidence of cortical reorganization of motor (M1) and somatosensory (S1) cortices, expanding from lip area to hand area, which correlated with pain scores. In addition, during imagined movement of the phantom hand, and executed movement of the intact hand, group maps demonstrated activation not only in bilateral M1 and S1 hand area, but also lip area, showing a two-way process of reorganization. In healthy participants, activation during lip purse and imagined and executed movement of the non-dominant hand was confined to the respective cortical representation areas only. Following training, patients reported a significant reduction in intensity and unpleasantness of constant pain and exacerbations, with a corresponding elimination of cortical reorganization. Post hoc analyses showed that intensity of constant pain, but not exacerbations, correlated with reduction in cortical reorganization. The results of this study add to our current understanding of the pathophysiology of PLP, underlining the reversibility of neuroplastic changes in this patient population while offering a novel, simple method of pain relief

Perioperative and long-term operative outcomes after surgery for trigeminal neuralgia: microvascular decompression vs percutaneous balloon ablation

<p>Abstract</p> <p>Objectives</p> <p>Numerous medical and surgical therapies have been utilized to treat the symptoms of trigeminal neuralgia (TN). This retrospective study compares patients undergoing either microvascular decompression or balloon ablation of the trigeminal ganglion and determines which produces the best long-term outcomes.</p> <p>Methods</p> <p>A 10-year retrospective chart review was performed on patients who underwent microvascular decompression (MVD) or percutaneous balloon ablation (BA) surgery for TN. Demographic data, intraoperative variables, length of hospitalization and symptom improvement were assessed along with complications and recurrences of symptoms after surgery. Appropriate statistical comparisons were utilized to assess differences between the two surgical techniques.</p> <p>Results</p> <p>MVD patients were younger but were otherwise similar to BA patients. Intraoperatively, twice as many BA patients developed bradycardia compared to MVD patients. 75% of BA patients with bradycardia had an improvement of symptoms. Hospital stay was shorter in BA patients but overall improvement of symptoms was better with MVD. Postoperative complication rates were similar (21% vs 26%) between the BA and MVD groups.</p> <p>Discussion</p> <p>MVD produced better overall outcomes compared to BA and may be the procedure of choice for surgery to treat TN.</p

Nanotools for Neuroscience and Brain Activity Mapping

Neuroscience is at a crossroads. Great effort is being invested into deciphering specific neural interactions and circuits. At the same time, there exist few general theories or principles that explain brain function. We attribute this disparity, in part, to limitations in current methodologies. Traditional neurophysiological approaches record the activities of one neuron or a few neurons at a time. Neurochemical approaches focus on single neurotransmitters. Yet, there is an increasing realization that neural circuits operate at emergent levels, where the interactions between hundreds or thousands of neurons, utilizing multiple chemical transmitters, generate functional states. Brains function at the nanoscale, so tools to study brains must ultimately operate at this scale, as well. Nanoscience and nanotechnology are poised to provide a rich toolkit of novel methods to explore brain function by enabling simultaneous measurement and manipulation of activity of thousands or even millions of neurons. We and others refer to this goal as the Brain Activity Mapping Project. In this Nano Focus, we discuss how recent developments in nanoscale analysis tools and in the design and synthesis of nanomaterials have generated optical, electrical, and chemical methods that can readily be adapted for use in neuroscience. These approaches represent exciting areas of technical development and research. Moreover, unique opportunities exist for nanoscientists, nanotechnologists, and other physical scientists and engineers to contribute to tackling the challenging problems involved in understanding the fundamentals of brain function