High spontaneous activity of C-nociceptors in painful polyneuropathy

Kleggetveit, Inge Petter; Namer, Barbara; Schmidt, Roland; Helås, Tormod; Rückel, Michael; Ørstavik, Kristin; Schmelz, Martin; Jørum, Ellen

doi:10.1016/j.pain.2012.05.017

Cited by 172 publications

(172 citation statements)

References 41 publications

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“…Spontaneous ongoing discharges of C-nociceptors are considered to be pathological causes of pain, and microneurography has been used to demonstrate that such spontaneous discharge is present in patients in whom pain is associated with SFN 200 . The same technique has been used to reveal spontaneous discharge of C-nociceptors in fibro myalgia 200,202,203 , thereby widening the spectrum of disorders that have been related to SFN.…”

Section: Microneurographymentioning

confidence: 99%

New technologies for the assessment of neuropathies

et al. 2017

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Peripheral neuropathies are among the most common neurological disorders 1 . In routine clinical practice, diagnosis of peripheral neuropathies is typically based on clinical assessment, nerve conduction studies and needle electromyography, which can determine whether symptoms are caused by primary axonal damage or demyelinating damage. This distinction is often relevant to therapeutic choices and to prognosis, as axonal damage typically reflects an inflammatory (for example, vasculitic) or degenerative (for example, hereditary or idiopathic) process that correlates with disability, whereas demyelinating damage can reflect a hereditary neuro pathy, but more often reflects an acquired immunemediated neuropathy. Besides metabolic, inflammatory or primary degenerative neuropathies, peripheral nerves can also be damaged by compression from adjacent tissue structures, such as tendons, cysts or haematomas. In this case, proper identification of the site, nature and degree of the lesion might be challenging, but is relevant to treatment and prognosis. Moreover, some patients present with symptoms that suggest damage to small nerve fibres, which nerve conduction studies cannot be used to detect.In the past 15 years, several techniques have become available to investigate focal and diffuse peripheral neuropathies, and their reliability has widened the spectrum of diagnostic tools for clinicians and improved assessment of neuropathies. In this Review, we provide an overview of these new and emerging technologies. We first discuss peripheral nerve imaging with MRI and ultrasonography, which can provide information about the precise localization of neuro pathies and the pathological processes involved in large-fibre neuropathies, and can complement clinical and electrophysiological evaluation. We then consider techniques that can provide diagnostic information when the pathological process is restricted to small nerve fibres and is consequently not detectable with nerve conduction studies or neuroimaging. These include skin biopsy, which is established in clinical practice, and the emerging techniques of corneal confocal microscopy, laser-evoked potentials and heat-related and pain-related evoked potentials, and microneurography.Nerve imaging technology Advances in imaging techniques have made it possible to gain great insight into nerve pathology with magnetic resonance and ultrasound. Each approach offers distinct advantages, and can provide different information about damage to large myelinated fibres. Abstract | Technical advances are rapidly changing the clinical and instrumental approach to peripheral nerve diseases. Magnetic resonance neurography, diffusion tensor imaging and nerve ultrasonography are increasingly entering the diagnostic workup of peripheral neuropathies as tools that complement neurophysiology and enable investigation of proximal structures, such as plexuses and roots. Progress in the design of magnetic resonance scanners and sequences, and the development of high-frequency ultrasound probes mean th...

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Section: Microneurographymentioning

confidence: 99%

New technologies for the assessment of neuropathies

et al. 2017

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“…Peripheral C-nociceptors were investigated by microneurography in a large series of patients with (11) and without (8) spontaneous pain (Kleggetveit et al, 2012). The mean percentage of C-nociceptors spontaneously active or mechanically sensitized was significantly higher in patients with pain.…”

Section: Polyneuropathymentioning

confidence: 99%

“…The difference was mainly due to more spontaneously active mechano-insensitive C-nociceptors, which were significantly higher in patients with pain compared to patients without pain, while the difference was much less prominent in mechano-sensitive (polymodal) C-nociceptors. The hyperexcitability of mechano-insensitive C-nociceptors may be a major factor underlying the pain experienced by patients with painful peripheral neuropathy (Kleggetveit et al, 2012).…”

Section: Polyneuropathymentioning

confidence: 99%

Microneurographic recording from unmyelinated nerve fibers in neurological disorders: An update

Donadio

Liguori

2015

Clinical Neurophysiology

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“…Indeed, the concept of biomarker is sometimes broadened to include many different kinds of measurements in pain patients, e.g. sensory phenotyping, intraepidermal nerve fiber counts, microneurography, electrophysiological recording of noxious stimulus-evoked cortical potentials, or different kinds of functional imaging [44,58,128,187,217,232]. However, referring to psychophysical tests as biomarkers is problematic (as discussed in section 5.3).…”

Section: Rationale For the Questmentioning

confidence: 99%

The Cerebrospinal Fluid in Severe Pain Conditions : Clinical, Pharmacological and Proteomic Aspects

Bäckryd¹

2015

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The treatment of both cancer pain and non-cancer chronic pain is still suboptimal. The overall aim of this PhD thesis was to conduct translational pain research at the interface between clinical pain medicine and the field of human proteomics, using the practice of intrathecal analgesia at our institution as a starting point. Hence, the cerebrospinal fluid (CSF) is at the centre of the present dissertation, both as a target for infusing analgesics (Papers I and II – clinical and pharmacological aspects) and as an important biofluid for human biomarker studies (Papers III and IV – proteomic aspects). In Paper I, 28 cases of intrathecal analgesia in cancer patients were prospectively followed. Movement-evoked breakthrough pain remained a major clinical problem throughout the study month despite otherwise successful intrathecal analgesia (defined as good control of spontaneous resting pain paralleled by a marked decrease of concomitant systemic opioid doses). This study therefore illustrates the importance of considering not only spontaneous resting pain but also movement-evoked breakthrough pain. In Paper II, an expert-based algorithm for trialing the intrathecal analgesic ziconotide by bolus injections was evaluated in an open-label study of 23 patients with chronic neuropathic pain. We found few responders (13%) according to the strict criteria of the algorithm, but ziconotide bolus injection trialing seems feasible. The predictive power of ziconotide bolus trialing remains unclear, and the pharmacological profile of ziconotide (with very slow tissue penetration due to high hydrophilicity) calls the rationale for ziconotide bolus trialing into question. In Paper III, we found low levels of beta-endorphin in the CSF of chronic neuropathic pain patients (n=15) compared to healthy controls (n=19). We speculate that this might indicate dysfunctional top-down control of nociception. Substance P levels in the CSF did not differ by univariate statistics. In Paper IV, the CSF proteome of 11 patients with chronic neuropathic pain and 11 healthy controls was exploratively studied, combining gel-based proteomics with multivariate data analysis. After eliminating four proteins associated with age, 32 proteins were found to highly discriminate between groups. Among these, the seven proteins having the highest discriminatory power between patients and controls were: one isoform of angiotensinogen, two isoforms of alpha-1-antitrypsin, three isoforms of haptoglobin, and one isoform of pigment epithelium-derived factor. In conclusion, this PhD thesis demonstrates the fruitfulness of studying the CSF, both as a target for infusing analgesics and as a potential mirror of the neurobiological processes involved in pathological pain conditions. The thesis points to the need for more research into the mechanisms of different pain conditions, in order to hopefully achieve the vision of mechanism-based pain diagnoses

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High spontaneous activity of C-nociceptors in painful polyneuropathy

Cited by 172 publications

References 41 publications

New technologies for the assessment of neuropathies

New technologies for the assessment of neuropathies

Microneurographic recording from unmyelinated nerve fibers in neurological disorders: An update

The Cerebrospinal Fluid in Severe Pain Conditions : Clinical, Pharmacological and Proteomic Aspects

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