Search

Recent studies have demonstrated that immunological disease progression is closely related to abnormal function of the central nervous system (CNS). Rheumatoid arthritis (RA) is a chronic, inflammatory synovitis-based systemic immune disease of unknown etiology. In addition to joint pathological damage, RA has been linked to neuropsychiatric comorbidities, including depression, schizophrenia, and anxiety, increasing the risk of neurodegenerative diseases in life. Immune cells and their secreted immune factors will stimulate the peripheral and central neuronal systems that regulate innate and adaptive immunity. The understanding of autoimmune diseases has largely advanced insights into the molecular mechanisms of neuroimmune interaction. Here, we review our current understanding of CNS comorbidities and potential physiological mechanisms in patients with RA, with a focus on the complex and diverse regulation of mood and distinct patterns of peripheral immune activation in patients with rheumatoid arthritis. And in our review, we also discussed the role that has been played by peripheral neurons and CNS in terms of neuron mechanisms in RA immune challenges, and the related neuron-immune crosstalk.

As animals mature from embryonic to adult stages, the skin grows and acquires specialized appendages, like hairs, feathers, and scales. How cutaneous blood vessels and sensory axons adapt to these dramatic changes is poorly understood. By characterizing skin maturation in zebrafish, we discovered that sensory axons are delivered to the adult epidermis in organized nerves patterned by features in bony scales. These nerves associate with blood vessels and osteoblasts above scales. Osteoblasts create paths in scales that independently guide nerves and blood vessels during both development and regeneration. By preventing scale regeneration and examining mutants lacking scales, we found that scales recruit, organize, and polarize axons and blood vessels to evenly distribute them in the skin. These studies uncover mechanisms for achieving comprehensive innervation and vascularization of the adult skin and suggest that scales coordinate a metamorphosis-like transformation of the skin with sensory axon and vascular remodeling.

Spinal root avulsion leads to paralysis and loss of sensory function. Surgical methods can improve motor function and ameliorate pain but sensory recovery in adults is poor. Previous studies have shown that cell transplantation or treatment with trophic factors can improve functional outcome in rodents after dorsal root transection or crush. Here, a dorsal root injury model, more similar to human avulsion injuries, was used. The aims of this thesis were to investigate the behaviour of different stem cells following transplantation to avulsed dorsal roots and asses their potential to serve as possible regenerative therapy. In paper I, different murine stem cell types were transplanted to avulsed dorsal roots in rats. Murine embryonic stem cells remained outside the spinal cord and were surrounded by glutamatergic terminals. Boundary cap neural crest stem cells (bNCSC) formed elongated bands outside the spinal cord and migrated to the spinal cord as single cells. In paper II, transplanted bNCSC were further characterized. bNCSC remaining outside the spinal cord expressed glial markers and were associated with different types of sensory fibres. bNCSC that migrated into the injured spinal cord expressed different neuronal markers. In paper III, effects of bNCSC transplantation on local vasculature and glial scar formation were studied. bNCSC increase angiogenesis in a non dose response manner and participate in boundary glial scar formation. In paper IV, bNCSC spinal migration was analysed using two different injury models - dorsal root transection and dorsal root avulsion. In addition, bNCSC capacity to support sensory regeneration was assessed and the results suggest that bNCSC do not support robust regeneration of avulsed afferents. In paper V, an in vitro stem cell model system was used to assess the possibility of using artificial nanomaterials to deliver differentiation factors. Cells treated with either soluble factors or particle-delivered factors showed similar

Spinal root avulsion leads to paralysis and loss of sensory function. Surgical methods can improve motor function and ameliorate pain but sensory recovery in adults is poor. Previous studies have shown that cell transplantation or treatment with trophic factors can improve functional outcome in rodents after dorsal root transection or crush. Here, a dorsal root injury model, more similar to human avulsion injuries, was used. The aims of this thesis were to investigate the behaviour of different stem cells following transplantation to avulsed dorsal roots and asses their potential to serve as possible regenerative therapy. In paper I, different murine stem cell types were transplanted to avulsed dorsal roots in rats. Murine embryonic stem cells remained outside the spinal cord and were surrounded by glutamatergic terminals. Boundary cap neural crest stem cells (bNCSC) formed elongated bands outside the spinal cord and migrated to the spinal cord as single cells. In paper II, transplanted bNCSC were further characterized. bNCSC remaining outside the spinal cord expressed glial markers and were associated with different types of sensory fibres. bNCSC that migrated into the injured spinal cord expressed different neuronal markers. In paper III, effects of bNCSC transplantation on local vasculature and glial scar formation were studied. bNCSC increase angiogenesis in a non dose response manner and participate in boundary glial scar formation. In paper IV, bNCSC spinal migration was analysed using two different injury models - dorsal root transection and dorsal root avulsion. In addition, bNCSC capacity to support sensory regeneration was assessed and the results suggest that bNCSC do not support robust regeneration of avulsed afferents. In paper V, an in vitro stem cell model system was used to assess the possibility of using artificial nanomaterials to deliver differentiation factors. Cells treated with either soluble factors or particle-delivered factors showed similar

Spinal root avulsion leads to paralysis and loss of sensory function. Surgical methods can improve motor function and ameliorate pain but sensory recovery in adults is poor. Previous studies have shown that cell transplantation or treatment with trophic factors can improve functional outcome in rodents after dorsal root transection or crush. Here, a dorsal root injury model, more similar to human avulsion injuries, was used. The aims of this thesis were to investigate the behaviour of different stem cells following transplantation to avulsed dorsal roots and asses their potential to serve as possible regenerative therapy. In paper I, different murine stem cell types were transplanted to avulsed dorsal roots in rats. Murine embryonic stem cells remained outside the spinal cord and were surrounded by glutamatergic terminals. Boundary cap neural crest stem cells (bNCSC) formed elongated bands outside the spinal cord and migrated to the spinal cord as single cells. In paper II, transplanted bNCSC were further characterized. bNCSC remaining outside the spinal cord expressed glial markers and were associated with different types of sensory fibres. bNCSC that migrated into the injured spinal cord expressed different neuronal markers. In paper III, effects of bNCSC transplantation on local vasculature and glial scar formation were studied. bNCSC increase angiogenesis in a non dose response manner and participate in boundary glial scar formation. In paper IV, bNCSC spinal migration was analysed using two different injury models - dorsal root transection and dorsal root avulsion. In addition, bNCSC capacity to support sensory regeneration was assessed and the results suggest that bNCSC do not support robust regeneration of avulsed afferents. In paper V, an in vitro stem cell model system was used to assess the possibility of using artificial nanomaterials to deliver differentiation factors. Cells treated with either soluble factors or particle-delivered factors showed similar

Spinal root avulsion leads to paralysis and loss of sensory function. Surgical methods can improve motor function and ameliorate pain but sensory recovery in adults is poor. Previous studies have shown that cell transplantation or treatment with trophic factors can improve functional outcome in rodents after dorsal root transection or crush. Here, a dorsal root injury model, more similar to human avulsion injuries, was used. The aims of this thesis were to investigate the behaviour of different stem cells following transplantation to avulsed dorsal roots and asses their potential to serve as possible regenerative therapy. In paper I, different murine stem cell types were transplanted to avulsed dorsal roots in rats. Murine embryonic stem cells remained outside the spinal cord and were surrounded by glutamatergic terminals. Boundary cap neural crest stem cells (bNCSC) formed elongated bands outside the spinal cord and migrated to the spinal cord as single cells. In paper II, transplanted bNCSC were further characterized. bNCSC remaining outside the spinal cord expressed glial markers and were associated with different types of sensory fibres. bNCSC that migrated into the injured spinal cord expressed different neuronal markers. In paper III, effects of bNCSC transplantation on local vasculature and glial scar formation were studied. bNCSC increase angiogenesis in a non dose response manner and participate in boundary glial scar formation. In paper IV, bNCSC spinal migration was analysed using two different injury models - dorsal root transection and dorsal root avulsion. In addition, bNCSC capacity to support sensory regeneration was assessed and the results suggest that bNCSC do not support robust regeneration of avulsed afferents. In paper V, an in vitro stem cell model system was used to assess the possibility of using artificial nanomaterials to deliver differentiation factors. Cells treated with either soluble factors or particle-delivered factors showed similar

Spinal root avulsion leads to paralysis and loss of sensory function. Surgical methods can improve motor function and ameliorate pain but sensory recovery in adults is poor. Previous studies have shown that cell transplantation or treatment with trophic factors can improve functional outcome in rodents after dorsal root transection or crush. Here, a dorsal root injury model, more similar to human avulsion injuries, was used. The aims of this thesis were to investigate the behaviour of different stem cells following transplantation to avulsed dorsal roots and asses their potential to serve as possible regenerative therapy. In paper I, different murine stem cell types were transplanted to avulsed dorsal roots in rats. Murine embryonic stem cells remained outside the spinal cord and were surrounded by glutamatergic terminals. Boundary cap neural crest stem cells (bNCSC) formed elongated bands outside the spinal cord and migrated to the spinal cord as single cells. In paper II, transplanted bNCSC were further characterized. bNCSC remaining outside the spinal cord expressed glial markers and were associated with different types of sensory fibres. bNCSC that migrated into the injured spinal cord expressed different neuronal markers. In paper III, effects of bNCSC transplantation on local vasculature and glial scar formation were studied. bNCSC increase angiogenesis in a non dose response manner and participate in boundary glial scar formation. In paper IV, bNCSC spinal migration was analysed using two different injury models - dorsal root transection and dorsal root avulsion. In addition, bNCSC capacity to support sensory regeneration was assessed and the results suggest that bNCSC do not support robust regeneration of avulsed afferents. In paper V, an in vitro stem cell model system was used to assess the possibility of using artificial nanomaterials to deliver differentiation factors. Cells treated with either soluble factors or particle-delivered factors showed similar

Spinal root avulsion leads to paralysis and loss of sensory function. Surgical methods can improve motor function and ameliorate pain but sensory recovery in adults is poor. Previous studies have shown that cell transplantation or treatment with trophic factors can improve functional outcome in rodents after dorsal root transection or crush. Here, a dorsal root injury model, more similar to human avulsion injuries, was used. The aims of this thesis were to investigate the behaviour of different stem cells following transplantation to avulsed dorsal roots and asses their potential to serve as possible regenerative therapy. In paper I, different murine stem cell types were transplanted to avulsed dorsal roots in rats. Murine embryonic stem cells remained outside the spinal cord and were surrounded by glutamatergic terminals. Boundary cap neural crest stem cells (bNCSC) formed elongated bands outside the spinal cord and migrated to the spinal cord as single cells. In paper II, transplanted bNCSC were further characterized. bNCSC remaining outside the spinal cord expressed glial markers and were associated with different types of sensory fibres. bNCSC that migrated into the injured spinal cord expressed different neuronal markers. In paper III, effects of bNCSC transplantation on local vasculature and glial scar formation were studied. bNCSC increase angiogenesis in a non dose response manner and participate in boundary glial scar formation. In paper IV, bNCSC spinal migration was analysed using two different injury models - dorsal root transection and dorsal root avulsion. In addition, bNCSC capacity to support sensory regeneration was assessed and the results suggest that bNCSC do not support robust regeneration of avulsed afferents. In paper V, an in vitro stem cell model system was used to assess the possibility of using artificial nanomaterials to deliver differentiation factors. Cells treated with either soluble factors or particle-delivered factors showed similar

Chronic pain constitutes an important and growing problem in society with large unmet needs with respect to treatment and clear implications for quality of life. Computational modeling is used to complement experimental studies to elucidate mechanisms involved in pain states. Models representing the peripheral nerve ending often address questions related to sensitization or reduction in pain detection threshold. In models of the axon or the cell body of the unmyelinated C-fiber, a large body of work concerns the role of particular sodium channels and mutations of these. Furthermore, in central structures: spinal cord or higher structures, sensitization often refers not only to enhanced synaptic efficacy but also to elevated intrinsic neuronal excitability. One of the recent developments in computational neuroscience is the emergence of computational neuropharmacology. In this area, computational modeling is used to study mechanisms of pathology with the objective of finding the means of restoring healthy function. This research has received increased attention from the pharmaceutical industry as ion channels have gained increased interest as drug targets. Computational modeling has several advantages, notably the ability to provide mechanistic links between molecular and cellular levels on the one hand and functions at the systems level on the other hand. These characteristics make computational modeling an additional tool to be used in the process of selecting pharmaceutical targets. Furthermore, large-scale simulations can provide a framework to systematically study the effects of several interacting disease parameters or effects from combinations of drugs., QC 20220308

Natural selection favors the evolution of brains that can capture fitness-relevant features of the environment's causal structure. We investigated the evolution of small, adaptive logic-gate networks (“animats”) in task environments where falling blocks of different sizes have to be caught or avoided in a ‘Tetris-like’ game. Solving these tasks requires the integration of sensor inputs and memory. Evolved networks were evaluated using measures of information integration, including the number of evolved concepts and the total amount of integrated conceptual information. The results show that, over the course of the animats' adaptation, i) the number of concepts grows; ii) integrated conceptual information increases; iii) this increase depends on the complexity of the environment, especially on the requirement for sequential memory. These results suggest that the need to capture the causal structure of a rich environment, given limited sensors and internal mechanisms, is an important driving force for organisms to develop highly integrated networks (“brains”) with many concepts, leading to an increase in their internal complexity. © 2014 Albantakis et al.

Natural selection favors the evolution of brains that can capture fitness-relevant features of the environment's causal structure. We investigated the evolution of small, adaptive logic-gate networks (“animats”) in task environments where falling blocks of different sizes have to be caught or avoided in a ‘Tetris-like’ game. Solving these tasks requires the integration of sensor inputs and memory. Evolved networks were evaluated using measures of information integration, including the number of evolved concepts and the total amount of integrated conceptual information. The results show that, over the course of the animats' adaptation, i) the number of concepts grows; ii) integrated conceptual information increases; iii) this increase depends on the complexity of the environment, especially on the requirement for sequential memory. These results suggest that the need to capture the causal structure of a rich environment, given limited sensors and internal mechanisms, is an important driving force for organisms to develop highly integrated networks (“brains”) with many concepts, leading to an increase in their internal complexity. © 2014 Albantakis et al.

Natural selection favors the evolution of brains that can capture fitness-relevant features of the environment's causal structure. We investigated the evolution of small, adaptive logic-gate networks (“animats”) in task environments where falling blocks of different sizes have to be caught or avoided in a ‘Tetris-like’ game. Solving these tasks requires the integration of sensor inputs and memory. Evolved networks were evaluated using measures of information integration, including the number of evolved concepts and the total amount of integrated conceptual information. The results show that, over the course of the animats' adaptation, i) the number of concepts grows; ii) integrated conceptual information increases; iii) this increase depends on the complexity of the environment, especially on the requirement for sequential memory. These results suggest that the need to capture the causal structure of a rich environment, given limited sensors and internal mechanisms, is an important driving force for organisms to develop highly integrated networks (“brains”) with many concepts, leading to an increase in their internal complexity. © 2014 Albantakis et al.

Natural selection favors the evolution of brains that can capture fitness-relevant features of the environment's causal structure. We investigated the evolution of small, adaptive logic-gate networks (“animats”) in task environments where falling blocks of different sizes have to be caught or avoided in a ‘Tetris-like’ game. Solving these tasks requires the integration of sensor inputs and memory. Evolved networks were evaluated using measures of information integration, including the number of evolved concepts and the total amount of integrated conceptual information. The results show that, over the course of the animats' adaptation, i) the number of concepts grows; ii) integrated conceptual information increases; iii) this increase depends on the complexity of the environment, especially on the requirement for sequential memory. These results suggest that the need to capture the causal structure of a rich environment, given limited sensors and internal mechanisms, is an important driving force for organisms to develop highly integrated networks (“brains”) with many concepts, leading to an increase in their internal complexity. © 2014 Albantakis et al.

1. Extracellular single-cell recordings were made from the cerebellar thalamus, the ventro-posterior lateralis par caudalis (VPL(c)) and motor cortex of three conscious monkeys. Recordings were made from the thalamus as well as the cortex in two monkeys. In all, recordings were made from the thalamus in four hemispheres and from the motor cortex in four hemispheres. The animals were trained to permit a detailed examination when relaxed. Unexpected perturbations were applied to the wrist. Seventy-seven wrist-related neurones were recorded in the cerebellar thalamus, forty-two neurones from the VPL(c) and eighty-four neurones in motor cortex. 2. Cerebellar nuclear stimulation was used to physiologically identify thalamic neurones receiving input from the cerebellum. The location of all neurones was verified histologically. 3. The majority of cerebellar thalamic neurones had deep sensory receptive fields related to a single muscle, a group of synergists or a single joint. There was a distinct topographical organization. These fields were similar to sensory fields in motor cortical neurones, but had higher thresholds. 4. VPL(c) neurones had discrete deep or cutaneous sensory fields, or a combination of these fields, which suggests convergence. VPL(c) neurones had fields with lower thresholds than cerebellar thalamic neurones. The somatotopically located forelimb area in the VPL(c) was posterior to and continuous with the forelimb area in the cerebellar thalamus. 5. VPL(c) neurones responded with a shorter latency to wrist perturbations than did cerebellar thalamic neurones. VPL(c) neurones with deep sensory fields changed firing significantly earlier than those with cutaneous fields. The VPL(c) is likely to be the major source of sensory input to the motor cortex, and based on the results of this study we suggest that the VPL(c) is the thalamic nucleus best placed to transmit short-latency afferent input from the forelimb. 6. The timing of the neuronal discharge of cere

1. Extracellular single-cell recordings were made from the cerebellar thalamus, the ventro-posterior lateralis par caudalis (VPL(c)) and motor cortex of three conscious monkeys. Recordings were made from the thalamus as well as the cortex in two monkeys. In all, recordings were made from the thalamus in four hemispheres and from the motor cortex in four hemispheres. The animals were trained to permit a detailed examination when relaxed. Unexpected perturbations were applied to the wrist. Seventy-seven wrist-related neurones were recorded in the cerebellar thalamus, forty-two neurones from the VPL(c) and eighty-four neurones in motor cortex. 2. Cerebellar nuclear stimulation was used to physiologically identify thalamic neurones receiving input from the cerebellum. The location of all neurones was verified histologically. 3. The majority of cerebellar thalamic neurones had deep sensory receptive fields related to a single muscle, a group of synergists or a single joint. There was a distinct topographical organization. These fields were similar to sensory fields in motor cortical neurones, but had higher thresholds. 4. VPL(c) neurones had discrete deep or cutaneous sensory fields, or a combination of these fields, which suggests convergence. VPL(c) neurones had fields with lower thresholds than cerebellar thalamic neurones. The somatotopically located forelimb area in the VPL(c) was posterior to and continuous with the forelimb area in the cerebellar thalamus. 5. VPL(c) neurones responded with a shorter latency to wrist perturbations than did cerebellar thalamic neurones. VPL(c) neurones with deep sensory fields changed firing significantly earlier than those with cutaneous fields. The VPL(c) is likely to be the major source of sensory input to the motor cortex, and based on the results of this study we suggest that the VPL(c) is the thalamic nucleus best placed to transmit short-latency afferent input from the forelimb. 6. The timing of the neuronal discharge of cere

Low frequency transcutaneous sensory nerve stimulation (LF-SNS) [International Patent PCT/AU2004/001079:nerve function and tissue healing (Khalil, Z.)] improves sensory nerve function and accelerates wound healing of older animals. Intervention(s): Double blind, placebo controlled randomised trial of LF-SNS for 5 minutes, twice daily for up to 12 weeks, on healing of chronic venous leg ulcers in older people. Four layer compression bandaging was the standard therapy. Outcome measures (methods): Wound healing and the rate of epithelialisation (calculated from serial wound area estimation), microvascular blood flow (measured using LASER Doppler flowmetry), transcutaneous oxygen tension (measured using a transcutaneous oxygen monitor, TCM 400 Radiometer). Sensory nerve activity (assessed via measuring electrical cutaneous perception threshold using the Neurometer CPT and the flare response to 5% capsaicin (a selective activator of C fibres). Participant(s): 14 older people with chronic venous ulcers randomly allocated to active (mean age 74.8+/-2.3 years) and 15 to Sham nerve stimulation (mean age 76.5+/-2.6 years). Result(s): Microvascular blood flow improved in all participants. A high proportion of wounds healed (~ 60%). There were trends for better C-fibre function and faster healing rates in the Active group (1.1+/-0.3 cm2/wk) compared to the Sham group (0.6+/-0.2 cm2/wk) but failed to reach statistical significance due to the small sample size. Conclusion(s): The improvement in microvascular blood flow in both groups was an unexpected finding that has not previously been described. Most likely this was due to the four layer compression bandaging provided to all participants. Improved microvascular blood flow may be a significant contributor to wound healing. The observed trends to increased healing rates and improvements in C-fibre function in the actively stimulated group compared to the sham group warrant further studies of LF-SNS as an adjunct therapy for chro

Low frequency transcutaneous sensory nerve stimulation (LF-SNS) [International Patent PCT/AU2004/001079:nerve function and tissue healing (Khalil, Z.)] improves sensory nerve function and accelerates wound healing of older animals. Intervention(s): Double blind, placebo controlled randomised trial of LF-SNS for 5 minutes, twice daily for up to 12 weeks, on healing of chronic venous leg ulcers in older people. Four layer compression bandaging was the standard therapy. Outcome measures (methods): Wound healing and the rate of epithelialisation (calculated from serial wound area estimation), microvascular blood flow (measured using LASER Doppler flowmetry), transcutaneous oxygen tension (measured using a transcutaneous oxygen monitor, TCM 400 Radiometer). Sensory nerve activity (assessed via measuring electrical cutaneous perception threshold using the Neurometer CPT and the flare response to 5% capsaicin (a selective activator of C fibres). Participant(s): 14 older people with chronic venous ulcers randomly allocated to active (mean age 74.8+/-2.3 years) and 15 to Sham nerve stimulation (mean age 76.5+/-2.6 years). Result(s): Microvascular blood flow improved in all participants. A high proportion of wounds healed (~ 60%). There were trends for better C-fibre function and faster healing rates in the Active group (1.1+/-0.3 cm2/wk) compared to the Sham group (0.6+/-0.2 cm2/wk) but failed to reach statistical significance due to the small sample size. Conclusion(s): The improvement in microvascular blood flow in both groups was an unexpected finding that has not previously been described. Most likely this was due to the four layer compression bandaging provided to all participants. Improved microvascular blood flow may be a significant contributor to wound healing. The observed trends to increased healing rates and improvements in C-fibre function in the actively stimulated group compared to the sham group warrant further studies of LF-SNS as an adjunct therapy for chro

Objectives: Venous leg ulcers represent a major clinical problem, with poor rates of healing. Ideal treatment is compression bandaging. The effect of compression on neurovascular tissues involved in wound repair is unclear. This study aims to assess the effect of four-layer compression therapy (40 mmHg) on neurovascular function and wound healing in people with chronic venous leg ulcers - 15 people (55 years or older) with venous leg ulcers for more than six weeks. Method(s): Basal microvascular perfusion measurement (MPM), oxygen tension (tcpO2) measured at sensor temperatures of 39degreeC and 44degreeC and sensory nerve function using electrical cutaneous perception thresholds (ECPT) at 5, 250 and 2000 Hz (corresponding to C, Adelta and Abeta fibres) were assessed adjacent to the ulcer site, and at a mirror location on the non-ulcerated limb. Testing was undertaken before and after therapy for 5-12 weeks of four-layer compression bandaging. Result(s): There was significant improvement in tcpO2 at 44degreeC and ECPT at 2000 Hz (P<0.05) compared with pre-intervention. Changes in basal MPM, tcpO2 at 39degreeC and ECPT at 5 and 250 Hz after compression therapy did not reach statistical significance. Conclusion(s): Four-layer compression bandaging in people with venous leg ulcers improved some components of neurovascularture in people with chronic venous leg ulcers. Whether this improvement has contributed to wound healing in this study requires further investigation. © 2007 Royal Society of Medicine Press.

TREK belongs to a subfamily of tandem pore domain K+ channels, and consists of three subunits, TREK-1, TREK-2 and TRAAK. We examined the distribution of TREK-1, TREK-2 and TRAAK immunoreactive neurons in rat trigeminal sensory neurons. In the trigeminal ganglia, 31%, 43% and 60% of neurons were immunoreactive for TREK-1, TREK-2 and TRAAK, respectively. Mean sizes of TREK-1, TREK-2 and TRAAK immunoreactive trigeminal ganglion neurons were 447 ± 185, 445 ± 23 and 492 ± 12 mm2, respectively. Furthermore, TREK channels were colocalized with cationic TRP channels, TRPV1, TRPV2 and TRPM8. TREK-1 immunoreactive neurons were colocalized with TRPV1 (57%), TRPV2 (11%) and TRPM8 (33%). TREK-2-immunoreactive neurons were colocalized with TRPV1 (33%), TRPV2 (9%) and TRPM8 (19%). TRAAK immunoreactive neurons were colocalized with TRPV1 (47%), TRPV2 (10%) and TRPM8 (22%). The present results revealed that TREK-1, TREK-2 and TRAAK channels colocalized with thermosensitive TRP channels in some small trigeminal ganglion neurons.

Background: A role for the transient receptor potential (TRP) A1 ion channel in rat lower urinary tract (LUT) sensation and disease has been proposed, but in the human LUT no information on TRPA1 activity is available. Objectives: To investigate the distribution of TRPA1 in the human urethra and to study the effect of TRPA1 agonists on isolated urethral strip preparations. Design, settings, and participants: Urethral specimens were obtained preoperatively from 10 patients and were freshly prepared for Western blot, immunohistochemistry, and functional in vitro investigations. Measurements: The expression patterns of TRPA1 were studied with Western blot and immunohistochemistry. The effects of allyl isothiocyanate (A1), cinnamaldehyde (CA), and NaHS (donor of H2S) on tension of urethral strips were investigated in tissue baths. Results and limitations: TRPA1 immunoreactivity (-IR) was found in nerve fibres in the suburothelial space and was also located to nerve fibres of the muscle layer. Single TRPA1-IR nerves extended into the urothelium. A majority, but not all TRPA1-IR nerves also expressed immunoreactivity for CGRP or TRPV1. In the urothelium, TRPV1 was located to the outer layers whereas TRPA1 was observed in basal urothelial cells. Interspersed between strands of smooth muscle cells of the urethral wall, TRPA1- and vimentin-IR cells containing central nuclei and slender cytoplasmatic extensions were observed. In functional experiments, TRPA1-agonists had no contractile effect in urethral preparations. After precontraction with phenylephrine, AI, CA, and NaHS caused concentration-dependent relaxations of urethral strip preparations.´ Conclusions: The localization of TRPA1 to nerves that also express TRPV1 and CGRP, and in urothelial cells and interstitial cells, as well as the findings that TRPA1 agonists can modify tone of urethral preparations, propose a role for TRPA1 in afferent and efferent sensory signaling of the human outflow region.

Neurography is the most objective and reliable measure of the peripheral nerve function, and it is used to diagnose both local and generalized neuropathies. Neurography can measure both motor and sensory nerve functions. The principle for sensory neurgraphy is to stimulate over the nerve and record proximal or distal from the stimulated electrode. At the Department of Clinical Neurophysiology, University Hospital Uppsala, a problem has been identified, in that young adult patients tend to show unexpected abnormal neurography values in relation to the expected, indicated by the reference limits, without clinical correlates. This concerns foremost the sensory amplitudes in median and ulnar nerves. The hypothesis is that the requirement of young adults’ amplitudes is too high. A reference material better including more subjects in this age group may solve the problem. Sensory nerve conduction studies were performed in 33 subjects, aged 15-30. The nerve functions were tested on median, ulnar and radial nerves. Surface electrodes were used for both recording and stimulation. The result shows that the presently used reference material for some nerves indeed has too high requirement for young adults. After increasing the reference material for younger age groups, the new reference limits has been changed and this should cause fewer false positive findings.

Neurography is the most objective and reliable measure of the peripheral nerve function, and it is used to diagnose both local and generalized neuropathies. Neurography can measure both motor and sensory nerve functions. The principle for sensory neurgraphy is to stimulate over the nerve and record proximal or distal from the stimulated electrode. At the Department of Clinical Neurophysiology, University Hospital Uppsala, a problem has been identified, in that young adult patients tend to show unexpected abnormal neurography values in relation to the expected, indicated by the reference limits, without clinical correlates. This concerns foremost the sensory amplitudes in median and ulnar nerves. The hypothesis is that the requirement of young adults’ amplitudes is too high. A reference material better including more subjects in this age group may solve the problem. Sensory nerve conduction studies were performed in 33 subjects, aged 15-30. The nerve functions were tested on median, ulnar and radial nerves. Surface electrodes were used for both recording and stimulation. The result shows that the presently used reference material for some nerves indeed has too high requirement for young adults. After increasing the reference material for younger age groups, the new reference limits has been changed and this should cause fewer false positive findings.

A new therapy using sensory nerve stimulation [International Patent Application Number PCT/AU2004/001079: 'nerve function and tissue healing' (Khalil, Z)] has been developed in our vascular physiology laboratory. This treatment has been found to improve the deficient sensory nerve function and associated deficient wound healing of older persons to levels seen in young people. An 82-year-old man with a small but persistent venous leg ulcer for 18 months, despite apparently appropriate wound dressings and compression therapy, was seen in a specialist wound management service. The patient's sensory and microvascular function was assessed in great detail using the vascular physiology laboratory techniques, and he was provided the sensory nerve stimulation therapy in addition to conventional therapy. His wound healed after 4 weeks. We report the case here. Prior to nerve stimulation therapy, cutaneous sensation, microvascular blood flow and oxygen tension were found to be reduced near the ulcer when compared with the opposite, non ulcerated leg. After therapy, oxygen tension and microvascular blood flow had improved. This case provides further evidence that sensory nerve stimulation therapy at the stipulated parameters improves wound healing. The observation that sensory nerve function improved provides support for the notion that improvement in healing is mediated by improved nerve function. © Blackwell Publishing Ltd and Medicalhelplines.com Inc 2005.

A new therapy using sensory nerve stimulation [International Patent Application Number PCT/AU2004/001079: 'nerve function and tissue healing' (Khalil, Z)] has been developed in our vascular physiology laboratory. This treatment has been found to improve the deficient sensory nerve function and associated deficient wound healing of older persons to levels seen in young people. An 82-year-old man with a small but persistent venous leg ulcer for 18 months, despite apparently appropriate wound dressings and compression therapy, was seen in a specialist wound management service. The patient's sensory and microvascular function was assessed in great detail using the vascular physiology laboratory techniques, and he was provided the sensory nerve stimulation therapy in addition to conventional therapy. His wound healed after 4 weeks. We report the case here. Prior to nerve stimulation therapy, cutaneous sensation, microvascular blood flow and oxygen tension were found to be reduced near the ulcer when compared with the opposite, non ulcerated leg. After therapy, oxygen tension and microvascular blood flow had improved. This case provides further evidence that sensory nerve stimulation therapy at the stipulated parameters improves wound healing. The observation that sensory nerve function improved provides support for the notion that improvement in healing is mediated by improved nerve function. © Blackwell Publishing Ltd and Medicalhelplines.com Inc 2005.

[No abstract available]

[No abstract available]

[No abstract available]

[No abstract available]