A radiological evaluation of phosphogypsum.

Phosphogypsum is the by-product resulting from phosphoric acid or phosphate fertilizer production. The phosphate are used in these chemical processes contains the naturally occurring radioactive material U and all its subsequent decay products. During processing, the U generally remains in the phosphoric acid product, while the daughter, 226Ra, tends to be concentrated in the phosphogypsum. Phosphogypsum has physical properties that make it useful as a sub-base for roadways, parking lots, and similar construction. A radiological evaluation, to determine exposures to workers mixing this material with a stabilizing agent (portland cement), was performed at a South Louisiana phosphoric acid chemical plant. Measurements of the 226Ra content of the phosphogypsum showed an average of 1.1 +/- 0.3 Bq g-1 (0.7-1.7 Bq g-1). The average measured gross gamma exposure rate on the phosphogypsum pile corresponded to a dose equivalent rate of 0.368 +/- 0.006 mu Sv h-1 (0.32-0.42 mu Sv h-1). Radon daughter concentrations measured on top of the phosphogypsum pile ranged from 0.0006 to 0.001 working levels. An analysis of the airborne 226Ra concentrations showed only background levels.     

MR angiography for the long-term follow-up of dissecting aneurysms of the extracranial internal carotid artery

OBJECTIVE: We used MR angiography to examine and follow up the changes of dissecting aneurysms of the extracranial internal carotid artery (ICA). MATERIALS AND METHODS: We retrospectively reviewed the records of 101 consecutive patients with dissecting aneurysms of the extracranial ICA. Twenty patients with 26 spontaneous dissecting aneurysms were followed up with MR angiography every 1-2 years (men, 16; women, four; age range, 28-67 years; mean age, 51 years). RESULTS: The mean duration of follow-up was 41 months (range, 10-93 months). At MR angiography follow-up, 20 aneurysms did not change, four decreased from their original size by 33-53% (mean, 43%), and two resolved. One patient had an asymptomatic recurrent dissecting aneurysm of the extracranial ICA. Clinically, no patient had a thromboembolic stroke or transient ischemic attack during the follow-up period. CONCLUSION: MR angiography revealed that dissecting aneurysms of the extracranial ICA remain stable, decrease in size, or resolve--but they do not increase in size.     

Spinal nerve injury increases the percentage of cold-responsive DRG neurons

We tested the hypothesis that cold allodynia, observed following nerve injury reflects change(s) in the cold responsiveness of sensory neurons. To test this hypothesis we assessed the impact of the spinal nerve ligation (SNL) model of nerve injury on the responses of cutaneous sensory neurons to cooling in vitro. Nerve injury induced a significant increase in the incidence of cold responsive cutaneous neurons in uninjured but not injured ganglia. Because an increase in the percentage of cold responsive neurons in uninjured ganglia should increase the total neuronal response to cooling of peripheral tissue, these findings suggest that cold allodynia reflects, at least in part, a change in sensory neurons.     

A Golgi study of neurons in the camel cerebellum (Camelus dromedarius)

Neurons in the cerebellar cortex of camels were studied using modified Golgi impregnation methods. Neurons were classified according to their position, morphology of their soma, density and distribution of dendrites, and the course of their axons. Accordingly, eight types of neurons were identified. Three types were found in the molecular layer: upper and lower stellate cells and basket cells, and four types were found in the granular layer: granule cells, Golgi Type II cells, Lugaro cells, and unipolar brush cells. Only the somata of Purkinje cells were found in the Purkinje cell layer. The molecular layer is characterized by the presence of more dendrites, dendritic spines, and transverse fibers. Golgi cells also show extensive dendritic branching and spines. The results illustrate the neuronal features of the camel cerebellum as a large mammal living in harsh environmental conditions. These findings should contribute to advancing our understanding of species-comparative anatomy in achieving better coordination of motor activity.     

Erratum to “Partial nerve injury induces electrophysiological changes in conducting (uninjured) nociceptive and non-nociceptive DRG neurons: Possible relationships to aspects of peripheral neuropathic pain and paresthesias” [Pain 153 (9) (2012) 1824–1836]

Partial nerve injury leads to peripheral neuropathic pain. This injury results in conducting/uninterrupted (also called uninjured) sensory fibres, conducting through the damaged nerve alongside axotomised/degenerating fibres. In rats seven days after L5 spinal nerve axotomy (SNA) or modified-SNA (added loose-ligation of L4 spinal nerve with neuroinflammation-inducing chromic-gut), we investigated (a) neuropathic pain behaviours and (b) electrophysiological changes in conducting/uninterrupted L4 dorsal root ganglion (DRG) neurons with receptive fields (called: L4-receptive-field-neurons). Compared to pretreatment, modified-SNA rats showed highly significant increases in spontaneous-foot-lifting duration, mechanical-hypersensitivity/allodynia, and heat-hypersensitivity/hyperalgesia, that were significantly greater than after SNA, especially spontaneous-foot-lifting. We recorded intracellularly in vivo from normal L4/L5 DRG neurons and ipsilateral L4-receptive-field-neurons. After SNA or modified-SNA, L4-receptive-field-neurons showed the following: (a) increased percentages of C-, Aδ-, and Aβ-nociceptors and cutaneous Aα/β-low-threshold mechanoreceptors with ongoing/spontaneous firing; (b) spontaneous firing in C-nociceptors that originated peripherally; this was at a faster rate in modified-SNA than SNA; (c) decreased electrical thresholds in A-nociceptors after SNA; (d) hyperpolarised membrane potentials in A-nociceptors and Aα/β-low-threshold-mechanoreceptors after SNA, but not C-nociceptors; (e) decreased somatic action potential rise times in C- and A-nociceptors, not Aα/β-low-threshold-mechanoreceptors. We suggest that these changes in subtypes of conducting/uninterrupted neurons after partial nerve injury contribute to the different aspects of neuropathic pain as follows: spontaneous firing in nociceptors to ongoing/spontaneous pain; spontaneous firing in Aα/β-low-threshold-mechanoreceptors to dysesthesias/paresthesias; and lowered A-nociceptor electrical thresholds to A-nociceptor sensitization, and greater evoked pain.     

Partial nerve injury induces electrophysiological changes in conducting (uninjured) nociceptive and nonnociceptive DRG neurons: Possible relationships to aspects of peripheral neuropathic pain and paresthesias

Partial nerve injury leads to peripheral neuropathic pain. This injury results in conducting/uninterrupted (also called uninjured) sensory fibres, conducting through the damaged nerve alongside axotomised/degenerating fibres. In rats seven days after L5 spinal nerve axotomy (SNA) or modified-SNA (added loose-ligation of L4 spinal nerve with neuroinflammation-inducing chromic-gut), we investigated a) neuropathic pain behaviours and b) electrophysiological changes in conducting/uninterrupted L4 dorsal root ganglion (DRG) neurons with receptive fields (called: L4-receptive-field-neurons). Compared to pretreatment, modified-SNA rats showed highly significant increases in spontaneous-foot-lifting duration, mechanical-hypersensitivity/allodynia, and heat-hypersensitivity/hyperalgesia, that were significantly greater than after SNA, especially spontaneous-foot-lifting. We recorded intracellularly in vivo from normal L4/L5 DRG neurons and ipsilateral L4-receptive-field-neurons. After SNA or modified-SNA, L4-receptive-field-neurons showed the following: a) increased percentages of C-, Ad-, and Ab-nociceptors and cutaneous Aa/b-low-threshold mechanoreceptors with ongoing/spontaneous firing; b) spontaneous firing in C-nociceptors that originated peripherally; this was at a faster rate in modified-SNA than SNA; c) decreased electrical thresholds in A-nociceptors after SNA; d) hyperpolarised membrane potentials in A-nociceptors and Aa/b-low-threshold-mechanoreceptors after SNA, but not C-nociceptors; e) decreased somatic action potential rise times in C- and A-nociceptors, not Aa/b-low-threshold-mechanoreceptors. We suggest that these changes in subtypes of conducting/uninterrupted neurons after partial nerve injury contribute to the different aspects of neuropathic pain as follows: spontaneous firing in nociceptors to ongoing/spontaneous pain; spontaneous firing in Aa/b-low-threshold-mechanoreceptors to dysesthesias/paresthesias; and lowered A-nociceptor electrical thresholds to A-nociceptor sensitization, and greater evoked pain.     

Differential ascending projections from neurons in the cat's lateral cervical nucleus

Extracellular microelectrode recordings were made from single cells of the lateral cervical nucleus (LCN) in cats anaesthetized with chloralose and paralysed with gallamine triethiodide. The cells were tested for antidromic activation from the contralateral medial lemniscus and the contralateral tectum. Seventytwo LCN units were recorded which projected to one or both targets. Sixty (83%) projected through the medial lemniscus, and of these 36 (50% of the total) also projected to the tectum, whereas 24 (33%) projected through the medial lemniscus only; 12 (17%) projected only to the tectum. Twenty-nine units (40%) were excited by moving hairs of the coat but not by pinch of the skin, and 9 (31%) of these projected to the tectum, 11 (38%) through the medial lemniscus and 9 (31%) to both targets. Forty units (56%) were excited by hair movement and noxious pinch, and 3 (7%) of these projected to the tectum, 10 (25%) through the medial lemniscus and 27 (68%) to both targets. Three units (4%) had no discernible receptive fields and they all projected through the medial lemniscus, but not to the tectum. Of the 12 units projecting only to the tectum, 11 had receptive fields completely or partially on the trunk. Units projecting either through the medial lemniscus only, or through the medial lemniscus and also into the tectum, had receptive fields more widely distributed: these included small fields on the fore- and hind feet, on the limbs and also, a minority, on the trunk. Units with glove- or stocking-like receptive fields projected through the medial lemniscus. The results show that while most LCN cells project through the medial lemniscus, those excited by hair movement alone preferentially project either to the tectum or through the medial lemniscus, but not by both routes. The differences in receptive field properties of the differently projecting units are discussed in terms of the possible functions of the spinocervical system.     

Blocking of cytokines signalling attenuates evoked and spontaneous neuropathic pain behaviours in the paclitaxel rat model of chemotherapy‐induced neuropathy

Background

Chemotherapy‐induced peripheral neuropathic pain (CIPNP) is a serious dose‐limiting neurotoxic effect of cancer drug treatment. The underlying mechanism(s) of this debilitating condition, which lacks effective drug treatment, is incompletely understood. However, neural–immune interactions, involving increased expression and release of cytokines, are believed to be involved. Here, we examined, in the paclitaxel rat model of CIPNP, whether plasma levels of 24 cytokines/chemokines change after paclitaxel treatment, and whether blocking of signalling of some of those cytokines would reverse/attenuate behavioural signs of CIPNP.

Methods

To achieve these objectives luminex, pharmacological and behavioural experiments were performed on male Wistar rats (250–300 g) 31 days after the last injection of paclitaxel (1 mg/kg, i.p. on four alternate days) as well as on control (vehicle‐treated) rats.

Results

Compared with control rats, plasma levels of IL‐1α, IL‐1β, IL‐6, TNF‐α, INF‐γ and MCP‐1 were significantly upregulated in paclitaxel‐treated rats. Blocking of TNF‐α signalling with etanercept (2 mg/kg, i.p.) or IL‐1β with IL‐1 receptor antagonist (IL‐1ra; 3 mg/kg, i.p.), significantly attenuated established mechanical and cold hypersensitivity as well as spontaneous pain behaviour (spontaneous foot lifting) 24 and 48 h postdrug treatment. Pharmacological blockade of MCP‐1/CCL2 signalling with a highly selective CCR2 receptor antagonist (S504393, 5 mg/kg, i.p.) also significantly reduced evoked, but not spontaneous, pain behaviours of CIPNP in paclitaxel‐treated rats at the same time points.

Conclusions

The findings support the notion that cytokines/chemokines, particularly TNF‐α, IL‐1 and MCP‐1, are involved in the pathophysiology of CIPNP and suggest that strategies that target their inhibition may be effective in treating CIPNP.

Significance

This study demonstrates that paclitaxel‐treated rats exhibit, in addition to indices of mechanical and cold hypersensitivity, a behavioural sign of spontaneous pain, the principal compliant of patients with neuropathic pain. This was accompanied by upregulation in plasma levels of key cytokines/chemokines (IL‐1α, IL‐1β, IL‐6, TNF‐α, INF‐γ and MCP‐1) 31 days post‐treatment. However, it is noteworthy that cytokine release, rather than nerve injury per se, may be causative of NP in this model of CIPNP. Nevertheless, our findings that pharmacological blockade of TNF‐α, IL‐1β and MCP‐1 attenuated both evoked and spontaneous pain suggest that strategies that target inhibition of these cytokines may be effective in treating CIPNP.     

The TTX-Resistant Sodium Channel Nav1.8 (SNS/PN3): Expression and Correlation with Membrane Properties in Rat Nociceptive Primary Afferent Neurons

We have examined the distribution of the sensory neuron-specific Na⁺ channel Na_v1.8 (SNS/PN3) in nociceptive and non-nociceptive dorsal root ganglion (DRG) neurons and whether its distribution is related to neuronal membrane properties. Na_v1.8-like immunoreactivity (Na_v1.8-LI) was examined with an affinity purified polyclonal antiserum (SNS11) in rat DRG neurons that were classified according to sensory receptive properties and by conduction velocity (CV) as C-, Aδ- or Aα/β. A significantly higher proportion of nociceptive than low threshold mechanoreceptive (LTM) neurons showed Na_v1.8-LI, and nociceptive neurons had significantly more intense immunoreactivity in their somata than LTM neurons. Results showed that 89, 93 and 60 % of C-, Aδ- and Aα/β-fibre nociceptive units respectively and 88 % of C-unresponsive units were positive. C-unresponsive units had electrical membrane properties similar to C-nociceptors and were considered to be nociceptive-type neurons. Weak positive Na_v1.8-LI was also present in some LTM units including a C LTM, all Aδ LTM units (D hair), about 10 % of cutaneous LTM Aα/β-units, but no muscle spindle afferent units. Na_v1.8-LI intensity was negatively correlated with soma size (all neurons) and with dorsal root CVs in A- but not C-fibre neurons. Na_v1.8-LI intensity was positively correlated with action potential (AP) duration (both rise and fall time) in A-fibre neurons and with AP rise time only in positive C-fibre neurons. It was also positively correlated with AP overshoot in positive neurons. Thus high levels of Na_v1.8 protein may contribute to the longer AP durations (especially in A-fibre neurons) and larger AP overshoots that are typical of nociceptors.