Surgical management for chronic pain

Chronic pain in the UK affects up to 43% of the population. The consequences include physical and psychological distress, loss of function, employment, family and social strain and increased utilization of healthcare services. Modern pain management services operate across primary, secondary and tertiary care and incorporate general practitioners, psychologists, physiotherapists, pharmacists, specialist nurses, pain physicians and surgeons. This allows for a coordinated approach to chronic pain, engaging the patient in a structured pathway from conservative measures, through to surgery if necessary. Surgical interventions have been utilized effectively throughout the 20^th century for the treatment of a variety of conditions, some of which are now effectively managed with improved pharmacological approaches or novel neuromodulation techniques. Ablative procedures that aim to permanently interrupt the pain pathway still represent the final solution for some conditions, particularly those with cancer associated pain; however, the search for less invasive, less risky measures continues. This is stimulated by an increased understanding of the neurobiology of pain transmission and the physiological changes which occur in persistent pain.     

Epidemiology of multiple sclerosis in the north-east (Grampian region) of Scotland--an update.

The north-east of Scotland (Grampian Region) has undergone three incidence and prevalence surveys, including the present one, since 1970. Results from these indicate a true increase in the prevalence of the disease in the region. The incidence of the disease has remained continuously high and shows a slightly upward trend. Literature on the subject of repeated surveys in different regions of the world has been reviewed in detail. The need for a prevalence study from the south of the British Isles has been emphasised in order to enable one to judge if the increase in Scotland is in keeping with the pattern in the whole of the British Isles. The familial incidence of the disease was noted to be virtually unchanged between the three surveys. Certain other aspects of aetiological significance have been analysed, viz, clustering of patients at birth or at onset of the disease; ages of occurrence of childhood viral infections such as measles, mumps, chickenpox and rubella; and the role of canine distemper infection.     

IDEC-131 (Anti-CD154), Sirolimus and Donor-Specific Transfusion Facilitate Operational Tolerance in Non-Human Primates

CD154-specific antibody therapy prevents allograft rejection in many experimental transplant models. However, initial clinical transplant trials with anti-CD154 have been disappointing suggesting the need for as of yet undetermined adjuvant therapy. In rodents, donor antigen (e.g., a donor blood transfusion), or mTOR inhibition (e.g., sirolimus), enhances anti-CD154's efficacy. We performed renal transplants in major histocompatibility complex-(MHC) mismatched rhesus monkeys and treated recipients with combinations of the CD154-specific antibody IDEC-131, and/or sirolimus, and/or a pre-transplant donor-specific transfusion (DST). Therapy was withdrawn after 3 months. Triple therapy prevented rejection during therapy in all animals and led to operational tolerance in three of five animals including donor-specific skin graft acceptance in the two animals tested. IDEC-131, sirolimus and DST are highly effective in preventing renal allograft rejection in primates. This apparently clinically applicable regimen is promising for human renal transplant trials.     

Intracerebroventricular injection of choline increases plasma oxytocin levels in conscious rats

In the present study, we examined the effect of intracerebroventricularly (i.c.v.) injected choline on both basal and stimulated oxytocin release in conscious rats. I.c.v. injection of choline (50–150 μg) caused time- and dose-dependent increases in plasma oxytocin levels under normal conditions. The increase in plasma oxytocin levels in response to i.c.v. choline (150 μg) was greatly attenuated by the pretreatment of rats with atropine (10 μg; i.c.v.), muscarinic receptor antagonist. Mecamylamine (50 μg; i.c.v.), a nicotinic receptor antagonist, failed to suppress the effect of 150 μg choline on oxytocin levels. Pretreatment of rats with 20 μg of hemicholinium-3 (HC-3), a specific inhibitor of choline uptake into nerve terminals, greatly attenuated the increase in plasma oxytocin levels in response to i.c.v. choline injection. Osmotic stimuli induced by either oral administration of 1 ml hypertonic saline (3 M) following 24-h dehydration of rats (type 1) or an i.c.v. injection of hypertonic saline (1 M) (type 2) increased plasma oxytocin levels significantly, but hemorrhage did not alter basal oxytocin concentrations. The i.c.v. injection of choline (50, 150 μg) under these conditions caused an additional and significant increase in plasma oxytocin concentrations beyond that produced by choline in normal conditions. These data show that choline can increase plasma oxytocin concentrations through the stimulation of central cholinergic muscarinic receptors by presynaptic mechanisms and enhance the stimulated oxytocin release.     

Cytoprotective actions of 2,4-dimethoxybenzylidene anabaseine in differentiated PC12 cells and septal cholinergic neurons

The potential cytoprotective actions of a novel nicotinic agent 2,4-dimethoxybenzilidene anabaseine (DMXB) were investigated in differentiated PC12 cells and transected rat septal cholinergic neurons in vivo. In NGF-differentiated PC12 cells, removal of both NGF and serum led to cell loss, a reduced % of cells expressing neurites, the release of lactate dehydrogenase, and a decrease in total cellular protein. Cell loss was apparent within 24 h, and remained constant between 4–8 days post-NGF removal. NGF alone (100 ng/ml), DMXB (10 μM), but not nicotine (10 μM), prevented these cell and neurite losses. DMXB-induced cytoprotection was blocked by 1 μM mecamylamine. DMXB (1 mg/kg, ip) injected twice but not once per day protected cholinesterase-staining septal neurons from retrograde degeneration following unilateral fimbrial transections. The twice per day DMXB injection-protocol also decreased cell roundness among cholinesterase-staining cells in the lesioned septal hemisphere compared to saline-injected animals. These studies suggest that DMXB may exert cytoprotective activity in NGF-sensitive neuronal populations. © 1994 Wiley-Liss, Inc.     

Clinical and radiological profile of symptomatic knee osteoarthritis in Malaysia

Aims: To create a clinical and radiological profile of patients with symptomatic osteoarthritis of the knee in Malaysia. Methods: One hundred consecutive patients presenting with symptomatic knee osteoarthritis at a private rheumatology clinic were profiled for demographic and clinical features. Anteroposterior weight‐bearing, skyline and lateral knee X‐rays were taken. Statistical Package for Social Sciences was used for data analysis. Results: Women predominated (93%). Fifty‐eight percent of the patients reported bilateral knee pain. Difficulty in walking, climbing and squatting was high (85%, 97% and 93% respectively). Patients with knee pain had a higher BMI than controls. Radiological abnormality, related to osteoarthritis was present in 97%. Osteophytes were generally tricompartmental while joint space narrowing was less evident in the lateral tibiofemoral joint than in the medial tibiofemoral joint and the patellofemoral joint. Almost half (49%) the patients manifested radiological varus deformity The severity of radiological abnormality increased with age. Although patients with unilateral pain had milder radiological abnormality, it tended to be bilateral. Clinically detectable hip abnormality and nodal osteoarthritis were uncommon, as was radiological chondrocalcinosis. Conclusions: Patients presenting with symptomatic knee osteoarthritis to a rheumatology service had a high degree of disability, radiological abnormality and varus deformity. Radiological abnormalities were essentially bilateral and tricompartmental.