Biomedical subjects

P Anand

Publications and source records attributed to P Anand.

At least 19 recordsLinked to original sources

PubMed2007

Motor recovery and the breathing arm after brachial plexus surgical repairs, including re-implantation of avulsed spinal roots into the spinal cord.

Forty-four patients with severe traction brachial plexus avulsion injuries were studied following surgical repairs. In eight patients, re-implanting avulsed spinal roots directly to the spinal cord was performed with other repairs and motor recovery in the proximal limb was similar to that achieved by conventional nerve grafts and transfers when assessed using the MRC clinical grades, Narakas scores, EMG and Transcranial Magnetic Stimulation (TMS). Thirty-four of the 37 patients had co-contractions of agonist and antagonist muscle groups. Spontaneous contractions of limb muscles in synchrony with respiration, the "breathing arm", were noted in 26 of 37 patients: in three patients, the source of the breathing arm was from spinal cord re-connection, providing evidence of regeneration from the CNS to the periphery. Our study shows that re-connection of avulsed spinal roots can produce good motor recovery and provides a clinical model for developing new treatments which may enhance nerve regeneration.

Adolescent↗

PubMed2006

Relocation of painful end neuromas and scarred nerves from the zone II territory of the hand.

This paper reports the results of treatment by proximal relocation of 46 painful end-neuromas or scarred nerves in 33 patients from the pre-defined Zone II of the hand. The relocated nerves included four palmar cutaneous branches of the median nerve, 17 dorsal branches of the ulnar nerves and 25 digital nerves. If no pain at the original site and no pain or only mild pain at the relocation site are considered an adequate treatment of these difficult problems, these relocation procedures achieve complete control of spontaneous baseline pain, complete control of spontaneous spikes of pain, 93% control of direct pressure pain, complete control of movement pain (excluding the extremes of movement of the wrist into extension, supination and, less frequently, pronation) and 96% control of hypersensitivity of the overlying skin.

Adolescent↗

PubMed2006

The potential role of nerve growth factor (NGF) in painful neuromas and the mechanism of pain relief by their relocation to muscle.

Painful neuromas have been successfully treated by surgical procedures including relocation to muscle, but the underlying molecular mechanism remains unclear. Nerve growth factor (NGF) is secreted by tissues and promotes the expression of ion channels and neuropeptides in sensory neurons involved in pain transmission. We hypothesised that excess of NGF may lead to pain in neuromas and that the efficacy of surgical relocation results from deprivation of NGF, i.e. translocation from NGF-rich regions, particularly sub-cutaneous structures associated with injury or inflammation, to NGF-poor structures such as muscle or bone. Using immunohistological methods with primary antibodies to rhNGF, we report that NGF levels were elevated in 13 painful neuromas in comparison with six control nerves. However, in four painful neuromata re-located into muscle with pain relief, the NGF level was similar to that of controls. NGF levels suggest an explanation for the development of painful neuromas and the efficacy of relocation.

Adult↗

PubMed2006

Pain phenomena and sensory recovery following brachial plexus avulsion injury and surgical repairs.

Seventy-six patients with severe brachial plexus avulsion injuries were studied using pain questionnaires and quantitative sensory testing. There was significant correlation between pain intensity and the number of roots avulsed prior to surgery (P=0.0004) and surgical repairs were associated with pain relief. Sensory recovery to thermal stimuli was observed, mainly in the C5 dermatome. Allodynia to mechanical and thermal stimuli was observed in the border zone of affected and unaffected dermatomes in 18% of patients assessed early (<6 months) and 37% patients at later stages. Pain and sensations referred to the original source of afferents occurred at a later stage (>6 months) in 12% of patients and were related to nerve regeneration. By contrast, "wrong-way" referred sensations (e.g. down the affected arm while shaving or drinking cold fluids) were reported by 44% of patients and often occurred early, suggesting CNS plasticity. Understanding sensory mechanisms will help develop new treatments for severe brachial plexus injuries.

Afferent Pathways↗

PubMed2006

The effect of neurotrophic factors on morphology, TRPV1 expression and capsaicin responses of cultured human DRG sensory neurons.

We have studied the effect of key neurotrophic factors (NTFs) on morphology, levels of the vanilloid receptor-1 (TRPV1) and responses to capsaicin in adult human sensory neurons in vitro. Avulsed dorsal root ganglia (DRG, n = 5) were cultured with or without a combination of nerve growth factor (NGF), glial cell (line)-derived growth factor (GDNF) and neurotrophin3 (NT3) for 5 days. In the absence of NTFs, the diameter of neurons ranged from 20 to 100 microm (mean 42 +/- 4 microm). Adding NTFs caused a significant increase in neuronal sizes, up to 120 microm (mean diameter 62 +/- 5 microm, P < 0.01, t-test), an overall 35% increase of TRPV1-positive neurons (P < 0.003), and notably of large TRPV1-positive neurons > 80 microm (P < 0.05). Responses to capsaicin were significantly enhanced with calcium ratiometry (P < 0.0001). Short duration (1h) exposure of dissociated sensory neurons to NTFs increased numbers of TRPV1-positive neurons, but not of TRPV3, Nav 1.8 and IK1 and the morphological size-distribution remained similar to intact post-mortem DRG neurons. NTFs thus increase size, elevate TRPV1 levels and enhance capsaicin responses in cultured human DRG neurons; these changes may relate to pathophysiology in disease states, and provide an in vitro model to study novel analgesics.

Adult↗

PubMed2006

Sotos syndrome with hypodontia.

Sotos syndrome, or cerebral gigantism, is a rare genetic condition characterized by tall stature, gigantism, dolichocephaly, advanced bone age and learning disability. The purpose of this case report is to highlight the dental management of a 10-year-old boy with Sotos syndrome who presented with hypodontia and dental caries.

Abnormalities, Multiple↗

PubMed2005

Sodium channel Nav1.8 immunoreactivity in painful human dental pulp.

BACKGROUND: The tetrodotoxin-resistant voltage-gated sodium channel Nav1.8 (SNS1/PN3) is expressed by nociceptors and may play a role in pain states. METHODS: Using specific antibodies for immunohistochemistry, we studied Nav1.8 immunoreactivity in human dental pulp in relation to the neuronal marker neurofilament. Human tooth pulp was extracted from teeth harvested from a total of twenty-two patients (fourteen without dental pain, eight patients with dental pain). RESULTS: Fibres immunoreactive for Nav1.8, were significantly increased on image analysis in the painful group: median (range) Nav1.8 to Neurofilament % area ratio, non-painful 0.059 (0.006-0.24), painful 0.265 (0.13-0.5), P = 0.0019. CONCLUSION: Nav1.8 sodium channels may thus represent a therapeutic target in trigeminal nerve pain states.

Journal Article↗

PubMed2005

Decreased sensory receptors P2X3 and TRPV1 in suburothelial nerve fibers following intradetrusor injections of botulinum toxin for human detrusor overactivity.

PURPOSE: Botulinum neurotoxin type A (BoNT/A) is effective in the treatment of intractable detrusor overactivity (DO). In addition to its known inhibitory effect on presynaptic release of acetylcholine by motor terminals, there is increasing evidence that BoNT/A may affect sensory fibers. We investigated a possible effect of BoNT/A on human bladder afferent mechanisms by studying the sensory receptors P2X3 and TRPV1 in biopsies from patients with neurogenic or idiopathic DO. MATERIALS AND METHODS: A total of 38 patients (22 with neurogenic DO, 16 with idiopathic DO) with intractable DO were treated with intradetrusor BoNT/A, and bladder biopsies were taken at 4 and 16 weeks. Urodynamics and voiding diary were also recorded. Specimens were studied immunohistochemically for P2X3, TRPV1 and the pan-neuronal marker PGP9.5, in comparison with controls. RESULTS: P2X3-immunoreactive and TRPV1-immunoreactive (-IR) fibers were decreased at 4 weeks after BoNT/A, and more significantly at 16 weeks (paired t test p=0.0004 and p=0.0008, respectively), when significant improvements were observed in clinical and urodynamic parameters. P2X3-IR fiber decrease was significantly correlated with reduction of urgency episodes at 4 and 16 weeks (p=0.0013 at 4 weeks and p=0.02 at 16 weeks), but not maximum cystometric capacity or detrusor pressures. TRPV1-IR fiber decrease showed a similar trend. PGP9.5-IR suburothelial fibers remained unchanged after treatment at both followups (p=0.85 and p=0.21 at 4 and 16 weeks, respectively). Urothelial cell P2X3-IR and TRPV1-IR also appeared unchanged. CONCLUSIONS: Decreased levels of sensory receptors P2X3 and/or TRPV1 may contribute to the clinical effect of BoNT/A in detrusor overactivity.

Adult↗

PubMed2005

Capabilities and health.

Sen's capabilities approach offers a radical generalisation of the conventional approach to welfare economics. It has been highly influential in development and many researchers are now beginning to explore its implications for health care. This paper contributes to the emerging debate by discussing two examples of such applications: first, at the individual decision making level, namely the right to die, and second, at the social choice level. For the first application, which draws on Nussbaum's list of capabilities, it is argued that many capabilities are ambiguously or indirectly related to the right to die, but the ability to form a concept of the good life and plan one's own life provides a direct justification for such a right. In the second application, the focus is specifically on healthcare rationing and it is argued that, although not committed to age based rationing, the capabilities approach provides a more natural justification of age related access to health care than the fair innings argument, which is often used to justify the alleged ageism inherent in quality adjusted life years (QALY) maximisation.

Age Factors↗

PubMed2005

Intraligamental analgesia for post-operative pain control in children having dental extractions under general anaesthesia.

AIM: This was to assess the effectiveness and safety of intraligamental local analgesia (ILA) for postoperative pain control in children having dental extractions under general anaesthesia (GA). The variables affecting the effectiveness of ILA were also investigated. METHODS: Data were collected from children having permanent molars extracted under GA using a randomised half mouth study design. ILA (bupivicaine 0.5% with 1:200,000 adrenaline) was used on the randomly assigned experimental side prior to extraction of the teeth, and the contralateral control side received no ILA. Children were interviewed pre- and post-operatively by the principal investigator (PA) who was blind to the side of ILA. Pre- and post-operative anxiety levels of each child were measured using the Venham Picture Test (VPT). Patients were asked to rate which side was better in terms of pain control, whether they felt numbness and whether they preferred the numbness. Their post-operative pain levels were also measured using the visual analogue scale (VAS). Self-inflicted trauma following ILA was noted. RESULTS: Thirty children, with a mean age of 11.3 years (SD+/-1.7) completed the study. None of the patients had self-inflicted soft tissue trauma following ILA. Nineteen children (63%) found that pain control was better post-operatively on the side with ILA. Twenty-one children (70%) reported numbness following ILA of whom 14 (67%) said that they preferred this. VAS scores were not significantly different between the experimental and control sides. A higher percentage of boys (85%) than girls (47%) rated the ILA side "better" (p = 0.034). VPT scores were significantly higher for girls postoperatively (p = 0.048). CONCLUSION: ILA was a useful and safe adjunct for postoperative pain control in children having permanent teeth extracted under GA. The technique was found to be more effective in boys than girls. However, less than half the children in this study preferred the side with numbness. Further research is needed to determine effective methods of pain control in children following dental GA and to investigate the reasons for gender differences of pain perception in children.

Adolescent↗

PubMed2004

Towards improved clinical and physiological assessments of recovery in spinal cord injury: a clinical initiative.

Clinical practice and scientific research may soon lead to treatments designed to repair spinal cord injury. Repair is likely to be partial in the first trials, extending only one or two segments below the original injury. Furthermore, treatments that are becoming available are likely to be applied to the thoracic spinal cord to minimise loss of function resulting from damage to surviving connections. These provisos have prompted research into the improvement of clinical and physiological tests designed (1) to determine the level and density of a spinal cord injury, (2) to provide reliable monitoring of recovery over one or two spinal cord segments, and (3) to provide indices of function provided by thoracic spinal root innervation, presently largely ignored in assessment of spinal cord injury. This article reviews progress of the Clinical Initiative, sponsored by the International Spinal Research Trust, to advance the clinical and physiological tests of sensory, motor and autonomic function needed to achieve these aims.

Animals↗

PubMed2004

Endothelial nitric oxide synthase expression in neurogenic urinary bladders treated with intravesical resiniferatoxin.

OBJECTIVE: To investigate endothelial nitric oxide synthase (eNOS) immunoreactivity in bladder biopsies from patients with neurogenic detrusor overactivity (NDO) before and after treatment with intravesical resiniferatoxin, and compare this with control material; the distribution of two other vascular markers, von Willebrand Factor (vWF) and the vascular endothelial growth factor (VEGF), was also studied. PATIENTS AND METHODS: Flexible cystoscopic bladder biopsies from eight controls investigated for asymptomatic microhaematuria and 19 patients with refractory spinal NDO enrolled in a clinical trial of intravesical treatment with escalating doses of resiniferatoxin were immunostained with polyclonal rabbit antibodies for eNOS, vWF and VEGF. Fewer baseline NDO specimens (eight) were available for vWF and VEGF staining. Computerized image analysis was used to quantify immunoreactivity, and the Mann-Whitney test for statistical analysis. RESULTS: eNOS immunoreactivity was found in the suburothelium and less often in the urothelium, with a distribution indicating a location in small blood vessels at the urothelium-suburothelium junction. Immunostaining for vWF showed a similar location. There was a trend to higher eNOS values before treatment in those responding than in those not responding to resiniferatoxin (P = 0.059), and a significant reduction in eNOS immunoreactivity after successful treatment (P = 0.016). VEGF staining was weaker but there was a significant increase in pretreatment biopsies of responders to resiniferatoxin (P = 0.048). Clinical and histopathology features were similar in both groups. CONCLUSIONS: The trend for higher eNOS expression in patients with NDO who responded to resiniferatoxin suggests that increased vasculature or vasodilatation in the suburothelium may be necessary for successful intravesical treatment. Further studies with more patients are required to confirm this relationship and to examine the mechanisms underlying changes in vasculature with levels of bladder overactivity.

Administration, Intravesical↗

PubMed2004

Parallel changes in bladder suburothelial vanilloid receptor TRPV1 and pan-neuronal marker PGP9.5 immunoreactivity in patients with neurogenic detrusor overactivity after intravesical resiniferatoxin treatment.

OBJECTIVE: To compare PGP9.5 and transient receptor potential vanilloid receptor (TRPV1) suburothelial immunoreactivity between controls and patients with spinal neurogenic detrusor overactivity (NDO) before and after treatment with intravesical resiniferatoxin, as suburothelial PGP9.5-staining nerve fibres decrease in patients with spinal NDO who respond to intravesical capsaicin, and TRPV1 is present on these suburothelial nerve fibres in normal and overactive human urinary bladder. PATIENTS AND METHODS: Patients with refractory NDO were enrolled in a prospective, randomized, parallel-group, double-blind, placebo-controlled trial using escalating doses of resiniferatoxin to a maximum of 1 micro mol/L. Flexible cystoscopic bladder biopsies obtained at baseline, 4 weeks after each instillation and at the time of maximum clinical response were compared with biopsies taken from control subjects. Frozen sections were incubated with rabbit antibodies to TRPV1 and PGP9.5, and assessed using standard immunohistochemical methods. PGP9.5 nerve density was analysed using a nerve-counting graticule by an observer unaware of sample origin. Another two independent observers unaware of each other's results used a random grading scale to evaluate TRPV1 nerve fibre density and intensity. The immunohistochemistry results were compared with histology findings (haematoxylin-eosin), and the Mann-Whitney test used to assess any differences (P < 0.05 significant) and the Pearson test for correlation. RESULTS: There were eight controls and 20 patients with spinal NDO, 14 (five clinical responders and nine not) who received the maximum dose of resiniferatoxin. There were more PGP9.5 and TRPV1 nerve fibres in patients with NDO than in controls (P = 0.007 and 0.002, respectively). Immunoreactivity before resiniferatoxin was similar in both groups for both PGP9.5 and TRPV1. In responders there were fewer PGP9.5 and TRPV1-positive fibres after treatment (P = 0.008 for each) but no change in those not responding. Changes after treatment for TRPV1 correlated well with those for PGP9.5 (r = 0.88, P < 0.001). CONCLUSIONS: The decrease of PGP9.5 and TRPV1 immunoreactive nerve fibres in responders to resiniferatoxin (to levels in control tissues) suggests that the increased numbers of nerve fibres in patients with NDO are mainly of sensory origin and express TRPV1. As baseline nerve fibre values were similar in responders and nonresponders, an additional factor may account for the difference in treatment outcome.

Administration, Intravesical↗

PubMed2004

EFNS guidelines on neuropathic pain assessment.

In September 2001, a Task Force was set up under the auspices of the European Federation of Neurological Societies with the aim of evaluating the existing evidence about the methods of assessing neuropathic pain and its treatments. This review led to the development of guidelines to be used in the management of patients with neuropathic pain. In the clinical setting a neurological examination that includes an accurate sensory examination is often sufficient to reach a diagnosis. Nerve conduction studies and somatosensory-evoked potentials, which do not assess small fibre function, may demonstrate and localize a peripheral or central nervous lesion. A quantitative assessment of the nociceptive pathways is provided by quantitative sensory testing and laser-evoked potentials. To evaluate treatment efficacy in a patient and in controlled trials, the simplest psychometric scales and quality of life measures are probably the best methods. A laboratory measure of pain that by-passes the subjective report, and thus cognitive influences, is a hopeful aim for the future.

Europe↗

PubMed2004

Correlation of nerve root pain with dermatomal sensory threshold and back pain with spinal movement in single level lumbar spondylosis.

We studied 27 patients with low back pain and unilateral L5 or S1 spinal nerve root pain. Significant radiological changes were restricted to the symptomatic root level, when compared with controls. Low back and leg pain were graded on a visual analogue scale. Dermatomal quantitative sensory tests revealed significant elevations of warm, cool and touch perception thresholds in the affected dermatome, compared with controls. These elevations correlated with root pain (warm v L5 root pain; r = 0.88, p < 0.0001), but not with back pain. Low back pain correlated with restriction of anteroposterior spinal flexion (p = 0.02), but not with leg pain. A subset of 16 patients underwent decompressive surgery with improvement of pain scores, sensory thresholds and spinal mobility. A further 14 patients with back pain, multilevel nerve root symptoms and radiological changes were also studied. The only correlation found was of low back pain with spinal movement (p < 0.002). We conclude that, in patients with single level disease, dermatomal sensory threshold elevation and restriction of spinal movement are independent correlates of sciatica and low back pain.

Adult↗

PubMed2003

Influence of human skin injury on regeneration of sensory neurons.

The regeneration of sensory nerve fibres is regulated by trophic factors released from their target tissue, particularly the basal epidermis, and matrix molecules. Means to modulate this response may be useful for the treatment of neuromas and painful hypertrophic scars and of sensory deficits in skin grafts and flaps. We have developed an in vitro model of sensory neuron regeneration on human skin in order to study the mechanisms of sensory dysfunction in pathological conditions. Adult rat sensory neurons were co-cultured with unfixed cryosections of normal or injured (crushed) human skin for 72 h. Neurons were immunostained for growth-associated protein-43 and the neurite lengths of neuronal cell bodies situated in various skin regions were measured. Two-way analysis of variance was performed. Neurites of sensory cell bodies on epidermis of normal skin were the shortest, with a mean +/- SEM of 75+/-10 micrometer, whereas those of cells on the dermo-epidermal junction were the longest, with a mean +/- SEM of 231+/-18 micrometer. Neurons on the dermo-epidermal junction of injured skin had significantly longer neurites than those on the same region of normal skin (mean +/- SEM = 289+/-21 micrometer). Regeneration of sensory neurons may be influenced by extracellular matrix molecules, matrix-binding growth factors and trophic factors. Altered substrate or trophic factors in injured skin may explain the increase of neurite lengths. This in vitro model may be useful for studying the molecular mechanisms of sensory recovery and the development of neuropathic pain following peripheral nerve injury.

Animals↗

PubMed2003

Sensory fibres expressing capsaicin receptor TRPV1 in patients with rectal hypersensitivity and faecal urgency.

BACKGROUND: Faecal urgency and incontinence with rectal hypersensitivity is a distressing, unexplained disorder that is inadequately treated. We aimed to determine whether expression of the heat and capsaicin receptor vanilloid receptor 1 (TRPV1 or VR1) was changed in rectal sensory fibres, and to correlate nerve fibre density with sensory abnormalities. METHODS: We compared full-thickness rectal biopsy samples from nine patients with physiologically characterised rectal hypersensitivity with tissue samples from 12 controls. Sensory thresholds to rectal balloon distension and heating the rectal mucosa were measured before biopsy. We assessed specimens with immunohistochemistry and image analysis using specific antibodies to TRPV1; nerve growth factor (NGF) receptor tyrosine kinase A; glial cell line-derived neurotrophic factor (GDNF); neuropeptides calcitonin gene-related peptide (CGRP) and substance P; the related vanilloid receptor-like protein (VRL) 2; glial markers S-100 and glial fibrillary acid protein (GFAP); and the nerve structural marker peripherin. FINDINGS: In rectal hypersensitivity, nerve fibres immunoreactive to TRPV1 were increased in muscle, submucosal, and mucosal layers: in the mucosal layer, the median% area positive was 0.44 (range 0.30-0.59) in patients who were hypersensitive and 0.11 (0.00-0.21) in controls (p=0.0005). The numbers of peripherin-positive fibres also increased in the mucosal layer (hypersensitive 3.00 [1.80-6.50], controls 1.20 [0.39-2.10]: (p=0.0002). The increase in TRVP1 correlated significantly with the decrease in rectal heat (p=0.03) and the distension (p=0.02) sensory thresholds. The thresholds for heat and distension were also significantly correlated (p=0.0028). Expression of nerve fibres positive for GDNF (p=0.001) and tyrosine kinase A (p=0.002) was also increased, as were cell bodies of the submucosal ganglia immunoreactive to CGRP (p=0.0009). INTERPRETATION: Faecal urgency and rectal hypersensitivity could result from increased numbers of polymodal sensory nerve fibres expressing TRPV1. The triggering factor or factors remain uncertain, but drugs that target nerve terminals that express this receptor, such as topical resiniferatoxin, deserve consideration.

Adult↗

PubMed2003

Capsaicin and menthol in the treatment of itch and pain: recently cloned receptors provide the key.

Topical capsaicin is reported to be an effective treatment for idiopathic intractable pruritus ani. While both capsaicin and menthol application produce a transient perianal burning sensation, only capsaicin relieves itching. Classical observations on functional desensitisation of nociceptors by capsaicin may explain the beneficial effects but the recent discovery of a range of receptors which respond to capsaicin, menthol, and temperature, and their expression in subsets of sensory nerve fibres, provides an exciting prospect towards advancing our understanding and treatment of sensory dysfunction.

Administration, Topical↗