Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): Somatosensory abnormalities in 1236 patients with different neuropathic pain syndromes

Neuropathic pain is accompanied by both positive and negative sensory signs. To explore the spectrum of sensory abnormalities, 1236 patients with a clinical diagnosis of neuropathic pain were assessed by quantitative sensory testing (QST) following the protocol of DFNS (German Research Network on Neuropathic Pain), using both thermal and mechanical nociceptive as well as non-nociceptive stimuli.     

Involvement of transient receptor potential vanilloid 1 receptors in protease-activated receptor-2-induced joint inflammation and nociception

Protease-activated receptor-2 (PAR-2) is a G-protein-coupled receptor activated through proteolytic cleavage. It is localized on epithelial, endothelial and inflammatory cells, as well as on transient receptor potential vanilloid 1 (TRPV1) receptor-expressing neurones. It plays an important role in inflammatory/nociceptive processes. Since there are few reports concerning PAR-2 function in joints, the effects of intraarticular PAR-2 activation on joint pain and inflammation were studied. Secondary hyperalgesia/allodynia, spontaneous weight distribution, swelling and inflammatory cytokine production were measured and the involvement of TRPV1 ion channels was investigated in rats and mice. Injection of the PAR-2 receptor agonist SLIGRL-NH₂ into the knee decreased touch sensitivity and weight bearing of the ipsilateral hindlimb in both species. Secondary mechanical allodynia/hyperalgesia and impaired weight distribution were significantly reduced by the TRPV1 antagonist SB366791 in rats and by the genetic deletion of this receptor in mice. PAR-2 activation did not cause significant joint swelling, but increased IL-1β concentration which was not influenced by the lack of the TRPV1 channel. For comparison, intraplantar SLIGRL-NH₂ evoked similar primary mechanical hyperalgesia and impaired weight distribution in both WT and TRPV1 deficient mice, but oedema was smaller in the knockouts. The inactive peptide, LRGILS-NH₂, injected into either site did not induce any inflammatory or nociceptive changes. These data provide evidence for a significant role of TRPV1 receptors in secondary mechanical hyperalgesia/allodynia and spontaneous pain induced by PAR-2 receptor activation in the knee joint. Although intraplantar PAR-2 activation-induced oedema is also TRPV1 receptor-mediated, primary mechanical hyperalgesia, impaired weight distribution and IL-1β production are independent of this channel.     

The frontotemporal peripheral nerves. Topographic variations of the supraorbital, supratrochlear and auriculotemporal nerves and their possible clinical significance

The peripheral topography of the supraorbital (SON) and supratrochlear (STN) nerves and the superficial temporal branch of the auriculotemporal nerve (ATN) was investigated in 10 cadavers. The aim was to define the optimal locations for anaesthetic nerve blocks, as well as to help surgeons prevent nerve injuries. Specific measurements on the nerve “exits” in relation to defined landmarks are presented. The variability of the supraorbital notches and peripheral branching of the dissected nerves suggests several methods for anaesthetic blocks in cases of surgical and clinical head pain. The optimum injection site for a selective SON block is 20-30 mm from the midline (range 15-33 mm) reinjection at 30-50 mm from the midline might complete inefficient nerve block. For selective SON block the distance between the main SON and STN branches (mean 15.3 mm) should also be considered. The ATN is best blocked at a point located at the level with and 10-15 mm (range 8-20 mm) anterior to the upper origin of the helix. Separate exits for the medial and lateral SON branches were observed in eight of the 20 nerves examined. Twenty of the 28 exits were foraminae completed by bony or connective tissue. In many cases both the SON and STN ascended close to the associated artery in six cases a tissue band covered the nerve and vessel at the orbital exit. Some of the observed structures associated with the nerve might be pain-generators, however the present study does not provide any evidence for such a hypothesis.     

北京市城区3—6岁幼儿感觉统合失调的现况调查

目的：调查3－6岁幼儿感觉统合失调的失调率及其分布,为探讨感觉统合失调的病因提供线索。方法：采用流行病学研究现况调查整群抽样的方法,以感觉统合诊断表调查北京市城近郊区有代表性的15所幼儿园及部分散居幼儿。结果：1526名3－6岁幼儿的轻度感觉统合失调率为28．5％,重度感觉统合失调率为8．9％,轻重度感觉统合失调率为29．4％。男孩和女孩感觉统合失调率分别为28．3％和30．7％。各项轻度和重度感觉统合失调率的年龄和性别分布差异无显著性。结论：感觉统合失调是值得重视的儿童发育问题,若早期干预,可全面促进感觉统合功能的改善。     

Osteopontin-immunoreactivity in the rat trigeminal ganglion and trigeminal sensory nuclei

Osteopontin-immunoreactivity (OPN-ir) was examined in the oro-facial tissues and trigeminal sensory nuclei (principal sensory nucleus and spinal trigeminal nucleus) to ascertain the peripheral ending and central projection of OPN-containing primary sensory neurons in the trigeminal ganglion (TG). No staining was observed using mouse monoclonal anti-OPN antibody preabsorbed with recombinant mature OPN. OPN-immunoreactive (ir) peripheral endings were classified into two types: encapsulated and unencapsulated types. Unencapsulated endings were subdivided into two types: simple and complex types. Simple endings were characterized by the thin neurite that was usually devoid of ramification. These endings were seen in the hard plate and gingiva. The complex type was characterized by the thick ramified neurite, and observed in the vibrissa, hard palate, and molar periodontal ligament. Encapsulated endings were found only in the hard palate. The trigeminal sensory nuclei contained OPN-ir cell bodies and neuropil. The neuropil was devoid of ir in laminae I and II of the medullary dorsal horn (MDH), and had various staining intensities in other regions of the trigeminal sensory nuclei. Transection of the infraorbital and inferior alveolar nerves caused an increase of OPN-ir intensity in ipsilateral TG neurons. The staining intensity of the neuropil also increased in the trigeminal sensory nuclei ipsilateral to the neurotomy excepting laminae I and II of the MDH. The present study indicates that OPN-ir primary sensory neurons in the TG innervate encapsulated and unencapsulated corpuscular endings. Such neurons probably project their central terminals to the trigeminal sensory nuclei except for the superficial laminae of the MDH.     

Painful or painless lower limb dysesthesias are highly predictive of peripheral neuropathy: Comparison of different diagnostic modalities

Dysesthesias of the lower limbs are a common complaint of patients and may be indicative of peripheral neuropathy. Here we investigated the prevalence and type of neuropathy in patients presenting with this complaint and compared the diagnostic performance of different diagnostic modalities. Forty‐two patients were recruited prospectively and underwent a clinical examination, nerve conduction studies, quantitative sensory testing (QST), and skin biopsy at the dorsum of the foot. All patients had a correlate for their dysesthesias in at least one diagnostic modality. Most patients (>90%) had signs of small fiber loss or dysfunction. In about half of all patients large fibers were also affected. Nerve conduction studies were abnormal in 23/42 patients (54.8%). Cold or warm detection thresholds in QST were abnormal in 15/42 (35.7%) patients. Decreased intraepidermal nerve fiber density (IENFD) was found in 37 patients (88.1%), including some patients with normal QST findings. Nearly all patients with pathological QST had a reduced IENFD, indicating a high positive predictive value (93%) of QST in screening for reduced IENFD as correlate for neuropathy. Therefore in all patients with lower limb dysesthesias of unknown origin, the non‐invasive methods of NCS and QST should be used and potentially complemented by skin biopsy.     

Ultrastructural Changes in Axons Following Exposure to Pulsed Radiofrequency Fields

Pulsed radiofrequency (PRF) fields applied by an electrode to neural structures, such as the peripheral sensory nociceptor axons and dorsal root ganglion, are clinically effective in reducing pain and other neuropathic syndromes. However, a full understanding of the underlying mechanisms by which this occurs has not yet been clarified. In this study, PRF is applied to the afferent axons of the sciatic nerves of rats. A standard radiofrequency (RF) electrode and RF generator is used to apply the RF signal output to the sciatic nerve using standard PRF parameters that have been successfully used in clinical practice. The ultrastructure of the treated axons is observed after 10 days by electron microscopy. A control, sham application is simultaneously applied to the contralateral sciatic nerve to provide a statistical differential comparison. It is found that the internal ultrastructural components of the axons show microscopic damage after PRF exposure, including: abnormal membranes and morphology of mitochondria, and disruption and disorganization of microfilaments and microtubules. The damage appears to be more pronounced for C-fibers than for A-delta and A-beta fibers. The results are discussed in terms of internal electric field strengths and thermodynamic parameters.     

Neuronal markers in allergic rhinitis: expression and correlation with sensory testing

INTRODUCTION: Although the role of immunoglobulin E-mediated hypersensitivity reactions in allergic rhinitis is well known, the relative contribution of sensory nerves to the symptoms of rhinitis is uncertain. This study looked at the level of specific neuronal markers including the nerve marker protein gene product 9.5 (PGP 9.5), sensory and autonomic neuropeptides, the capsaicin/heat receptor TRPV1, and nerve growth factor (NGF) in patients with allergic rhinitis and controls and their correlation with nasal sensitivity. MATERIALS AND METHODS: Forty patients (23 controls, 17 rhinitis) having nasal surgery were recruited. Nasal sensitivity was tested using graded monofilaments. Inferior turbinate biopsies were collected and studied using immunohistology, with measurement of nerve fibers by direct observation or computerized image analysis. RESULTS: Nerve fibers (PGP 9.5) in the epithelium, subepithelium, and glandular/vascular regions were significantly increased in allergic rhinitis (P=.037, <.01, and .04, respectively), as were subepithelial and glandular/vascular fibers immunoreactive for neuropeptide substance P (P=.04 subepithelium; .02 glandular/vascular) and neuropeptide tyrosine (P<.01 glandular/vascular), markers for sensory and sympathetic nerves, respectively. TRPV1 epithelial fiber counts were higher in rhinitis, but this was not statistically significant. Epithelial NGF immunoreactivity (% area) was significantly increased in rhinitis (P=.027). Nasal sensitivity was correlated significantly with PGP 9.5 subepithelial innervation (control touch P=.023, irritation P=.046; rhinitis touch P=.042, irritation P=.043). A correlation was also observed between epithelial NGF and subepithelial PGP 9.5 innervation, which included all subjects (P=.044). CONCLUSION: The increased number and specific phenotypical changes of sensory nerves may play a role in nasal hypersensitivity and provide new targets for the treatment of rhinitis.     

Paradoxical vocal fold motion: a sensory-motor laryngeal disorder

OBJECTIVES: The purpose of this study is to determine the laryngeal sensitivity (LS) thresholds and the ratings of laryngopharyngeal reflux symptoms in patients with paradoxical vocal fold motion (PVFM). METHODS: This is a chart review following Institutional Review Board approval of 75 patients from January 2006 to June 2007. The patients were diagnosed with PVFM following case history, transnasal flexible laryngoscopy and spirometric testing. The data analyzed consisted of the reflux symptom index (RSI) and laryngopharyngeal sensitivity (LS). Laryngeal sensitivity and RSI were graded according to mild, moderate, or severe. RESULTS: There were 12 (16%) patients with normal RSI scores, 37 patients (49.3%) with moderate RSI (RSI 11-22), and 26 patients (34.7%) with severe RSI (RSI >22). The right LS was normal in 11 patients (14.7%), moderately impaired in 16 patients (21.3%), and severely impaired in 48 (64%) patients. The left LS showed normal sensation in 11 patients (14.7%), moderately impaired LS in 13 patients (17.3%), and severe impairment in 51 patients (68%). Only one patient had both normal sensation and normal RSI, and 70.4% of patients had abnormal RSI and sensation thresholds. CONCLUSIONS: Patients diagnosed with PVFM had a high prevalence of symptoms related to LPR and markedly reduced LS. These findings suggest that PVFM may be triggered by reduced peripheral sensation or laryngeal inflammation.     

Colonic mechanoreceptor inputs to rat lumbo-sacral dorsal horn neurones: distribution, thresholds and chemosensory modulation.

In order to better understand the central processing of visceral sensory information, we studied the responses of lumbo-sacral dorsal horn (L4-S1) neurones to colonic stimuli in anaesthetized rats. Twenty-four neurones responded to distal colonic distension with a 2.5-cm balloon; six of these were tested with proximal colonic distension, to which none responded. All neurones tested responded to somatic non-noxious inputs (tail movement). Responses to colonic distension were excitatory (n=22) or inhibitory (n=2). Sixteen neurones responded at a threshold of 20 mmHg or less, five at 20-40 mmHg, and three at 40-80 mmHg. Three of 10 neurones tested showed increased responses to colonic distension after intraluminal perfusion with bile. Bile itself did not evoke a response. We conclude that lumbo-sacral spinal neurones selectively receive mechanosensory inputs from the distal colon. Neurones respond at thresholds within and above the physiological range. Dorsal horn neurones receiving colonic mechanosensory inputs are not directly modulated by chemosensory inputs, but their responsiveness to distension may be augmented.