Neuropathic pain: the scope of the problem

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Laser evoked potentials in patients with trigeminal disease: the absence of Adelta potentials does not unmask C-fibre potentials.

[IF 2.468] Objective: Although laser stimuli activate both Ad- and C-fibres, the corresponding laser evoked potentials (LEPs) remain restricted to the Ad-fibre input. Previous studies found C-LEPs after limb stimulation only in subjects with block or clinical impairment of Ad-fibres. In this study, we aimed at verifying whether in the trigeminal territory the impairment of Ad-fibres unmasks the C-LEP. Methods: By collecting retrospectively LEPs recorded in 370 patients, we analyzed the results from 150 trigeminal divisions with absent Ad-LEPs. Results: We found signals that were consistent with the C-fibre input in three patients only. In most patients with absent Ad-LEPs, however, laser stimuli still elicited the Ad-conveyed pinprick sensation. Conclusions: The preserved pinprick sensation suggests that the Ad-fibre volley, though weakened, reached the cortex. The C-LEP absence may be explained according to the first come first served hypothesis: the evoked potential related to an afferent volley reaching the cortex shortly after a preceding input (i.e. a C-fibre volley coming after an Ad-fibre) will be suppressed. Significance: In clinical studies using the standard laser pulses to evoke the Ad-LEPs, the finding of absent signals does not indicate a concomitant impairment of C-fibres

Triggering trigeminal neuralgia

Introduction: Although it is widely accepted that facial pain paroxysms triggered by innocuous stimuli constitute a hallmark sign of trigeminal neuralgia, very few studies to date have systematically investigated the role of the triggers involved. In the recently published diagnostic classification, triggered pain is an essential criterion for the diagnosis of trigeminal neuralgia but no study to date has been designed to address this issue directly. In this study, we set out to determine, in patients with trigeminal neuralgia, how frequently triggers are present, which manoeuvres activate them and where cutaneous and mucosal trigger zones are located. Methods: Clinical characteristics focusing on trigger factors were collected from 140 patients with trigeminal neuralgia, in a cross-sectional study design. Results: Provocation of paroxysmal pain by various trigger manoeuvres was reported by 136 of the 140 patients. The most frequent manoeuvres were gentle touching of the face (79%) and talking (54%). Trigger zones were predominantly reported in the perioral and nasal region. Conclusion: This study confirms that in trigeminal neuralgia, paroxysmal pain is associated with triggers in virtually all patients and supports the use of triggers as an essential diagnostic feature of trigeminal neuralgia

Acetyl-L-carnitine in painful peripheral neuropathy: a systematic review

Acetyl-L-carnitine (ALC) has shown a neuroprotective effect in patients with peripheral neuropathies of different etiologies. Preclinical studies demonstrated a central anti-nociceptive action, both in neuropathic and nociceptive pain models. The present review aims to provide the knowledge on the efficacy of ALC in patients with painful peripheral neuropathy, based on the evidence. Consistent with the PRISMA statement, authors searched PubMed, Embase and the Cochrane Database of Systematic Reviews for relevant papers, including those issued before April 2018. Two authors independently selected studies for inclusion and data extraction: only trials including patients with a diagnosis of peripheral neuropathy and involving at least 10 patients were considered for the purposes of this review. Fourteen clinical trials were revised, to provide the level of evidence for neuropathy. To assess the global efficacy of ALC in painful peripheral neuropathy, a meta-analysis of four randomized controlled trials was performed. Mean difference in pain reduction as measured on a 10-cm VAS, and 95% CIs were used for pooling continuous data from each trial. Four randomized controlled trials tested ALC in patients with neuropathy secondary to diabetes and to antiretroviral therapy for HIV. Compared to placebo, ALC produced a significant pain reduction equal to 20.2% (95% CI: 8.3%-32.1%, P<0.0001) with respect to baseline. Clinical trials also showed beneficial effects on nerve conduction parameters and nerve fiber regeneration, with a good safety profile. These data indicate that ALC provides an effective and safe treatment in patients with painful peripheral neuropathy. We recommend further studies to assess the optimal dose and duration of the therapeutic effect (also after treatment withdrawal)

N-acetyl-cysteine, a drug that enhances the endogenous activation of group-II metabotropic glutamate receptors, inhibits nociceptive transmission in humans.

Emerging research seeking novel analgesic drugs focuses on agents targeting group-II metabotropic glutamate receptors (mGlu2 and mGlu3 receptors). N-Acetylcysteine (NAC) enhances the endogenous activation of mGlu2/3 receptors by activating the glial glutamate:cystine membrane exchanger. Here, we examined whether NAC inhibits nociceptive responses in humans and animals. We tested the effect of oral NAC (1.2 g) on thermal-pain thresholds and laser-evoked potentials in 10 healthy volunteers, according to a crossover, double-blind, placebo-controlled design, and the effect of NAC (100 mg/kg, i.p.) on the tail-flick response evoked by radiant heat stimulation in mice.In healthy subjects, NAC treatment left thermal-pain thresholds unchanged, but significantly reduced pain ratings to laser stimuli and amplitudes of laser-evoked potentials. NAC induced significantly greater changes in these measures than placebo. In the tail-flick test, NAC strongly reduced the nocifensive reflex response to radiant heat. The action of NAC was abolished by the preferential mGlu2/3 receptor antagonist, LY341495 (1 mg/kg, i.p.).Our findings show for the first time that NAC inhibits nociceptive transmission in humans, and does the same in mice by activating mGlu2/3 receptors. These data lay the groundwork for investigating the therapeutic potential of NAC in patients with chronic pain

Trigeminal sensory pathway function in patients with SUNCT

[IF 2.64] Objective: Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) is a rare primary headache whose origins are unclear. To seek information on its pathophysiology, we studied the trigeminal Ab and Ad pathways by recording trigeminal reflexes and laser evoked potentials (LEPs) in patients with SUNCT. Methods: Trigeminal reflexes and LEPs were recorded in 11 consecutive patients. Ten patients had neuroimaging evidence documenting idiopathic SUNCT and one had a posterior fossa tumour that compressed the trigeminal nerve thus causing symptomatic SUNCT. Results: Whereas the patients with idiopathic SUNCT had normal trigeminal reflex and LEP responses, the patient with symptomatic SUNCT had abnormal responses. Conclusions: Our neurophysiological findings show that idiopathic SUNCT spares the trigeminal sensory pathways whereas symptomatic SUNCT does not. Significance: Neurophysiological testing can easily differentiate the idiopathic and symptomatic forms of SUNCT. It also suggests that the two forms are pathophysiologically distinct entities

Pain-motor integration in the primary motor cortex in Parkinson's disease

In Parkinson's disease (PD), the influence of chronic pain on motor features has never been investigated. We have recently designed a technique that combines nociceptive system activation by laser stimuli and primary motor cortex (M1) activation through transcranial magnetic stimulation (TMS), in a laser-paired associative stimulation design (Laser-PAS). In controls, Laser-PAS induces long-term changes in motor evoked potentials reflecting M1 long-term potentiation-like plasticity, arising from pain-motor integration

Familial trigeminal neuralgia - a systematic clinical study with a genomic screen of the neuronal electrogenisome

OBJECTIVE: This cross-sectional study examined, for the first time, a large cohort of patients with trigeminal neuralgia, to ascertain the occurrence of familial cases, providing a systematic description of clinical features of familial disease. Since there is evidence linking hyperexcitability of trigeminal ganglion neurons to trigeminal neuralgia, we also carried out an exploratory genetic analysis of the neuronal electrogenisome in these patients. METHODS: We recorded familial occurrence by systematically interviewing all patients with a definite diagnosis of classical or idiopathic trigeminal neuralgia. We found 12 occurrences of trigeminal neuralgia with positive family history out of 88 enrolled patients. Whole-exome sequencing was carried out in 11 patients. We concentrated on the genetic variants within

Prevalence and time course of post-stroke pain: A multicenter prospective hospital-based study

OBJECTIVE: Pain prevalence data for patients at various stages after stroke. DESIGN: Repeated cross-sectional, observational epidemiological study. SETTING: Hospital-based multicenter study. SUBJECTS: Four hundred forty-three prospectively enrolled stroke survivors. METHODS: All patients underwent bedside clinical examination. The different types of post-stroke pain (central post-stroke pain, musculoskeletal pains, shoulder pain, spasticity-related pain, and headache) were diagnosed with widely accepted criteria during the acute, subacute, and chronic stroke stages. Differences among the three stages were analyzed with χ(2)-tests. RESULTS: The mean overall prevalence of pain was 29.56% (14.06% in the acute, 42.73% in the subacute, and 31.90% in the chronic post-stroke stage). Time course differed significantly according to the various pain types (P < 0.001). The prevalence of musculoskeletal and shoulder pain was higher in the subacute and chronic than in the acute stages after stroke; the prevalence of spasticity-related pain peaked in the chronic stage. Conversely, headache manifested in the acute post-stroke stage. The prevalence of central post-stroke pain was higher in the subacute and chronic than in the acute post-stroke stage. Fewer than 25% of the patients with central post-stroke pain received drug treatment. CONCLUSIONS: Pain after stroke is more frequent in the subacute and chronic phase than in the acute phase, but it is still largely undertreated

Identification of low intratumoral gene expression heterogeneity in neuroblastic tumors by genome-wide expression analysis and Game Theory

BACKGROUND. Neuroblastic tumors (NTs) are largely comprised of neuroblastic (Nb) cells with various quantities of Schwannian stromal (SS) cells. NTs show a variable genetic heterogeneity. NT gene expression profiles reported so far have not taken into account the cellular components. The authors reported the genome-wide expression analysis of whole Minors and microdissected Nb and SS cells. METHODS. The authors analyzed gene expression profiles of 10 stroma-poor NTs (NTs-SP) and 9 stroma-rich NTs (NTS-SR) by microarray technology. Nb and SS cells were. isolated by laser microdissection from NTs-SP and NTs-SR and probed with microarrays. Gene expression data were analyzed by the Significance Analysis of Microarrays (SAM) and Game Theory (GT) methods, the latter applied for the first time to microarray data evaluation. RESULTS. SAM identified 84 genes differentially expressed between NTs-SP and NTs-SR, whereas 50 were found by GT. NTs-SP mainly express genes associated with cell replication, nervous system development, and antiapoptotic pathways, whereas NTs-SR express genes of cell-cell communication and apoptosis. Combining SAM and GT, the authors found 16 common genes driving the separation between NTs-SP and NTs-SR. Five genes overexpressed in NTs-SP encode for nuclear proteins (CENPE, EYA1, PBK TOP2A, TFAP2B), whereas only 1 of 11 highly expressed genes in NTs-SR encodes for a nuclear receptor (NR4A2). CONCLUSIONS. The results showed that NT-SP and NT-SR gene signatures differ for a set of genes involved in distinct pathways, and the authors demonstrated a low intratumoral heterogeneity at the mRNA level in both NTs-SP and NTs-SR. The combination of SAM and GT methods may help to better identify gene expression profiling in NTs